http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15978060&query_hl=1
Pineal Res. 2005 Aug;39(1):73-6.
Serum melatonin circadian profiles
in women suffering from cervical cancer.
Karasek M, Kowalski AJ, Suzin J, Zylinska
K, Swietoslawski J.
Chair of Pathomorphology, Department of Electron Microscopy,
Polish Mother's Memorial Hospital-Research Institute, Medical
University of Lodz, Lodz, Poland.
Although there is an increasing evidence that the pineal
gland may play a role in human malignancy, the studies on
melatonin concentrations in different types of malignant tumors
brought about controversial results. However, changes in melatonin
concentrations have been observed in some types of human malignant
tumors. Therefore, we decided to study the circadian melatonin
rhythm in patients suffering from cervical cancer in different
stages of progression and to compare them with those in subjects
free from neoplastic disease. A total of 45 women were analyzed
in this study. The subjects were divided into two groups.
The first group consisted of 31 patients [mean age 52.1 +/-
1.8 yr (mean +/- S.E.M.), range 32-77 yr] with cervical cancer
in various stages of the disease. The second group consisted
of 14 healthy volunteers [mean age 53.5 +/- 2.0 yr (mean +/-
S.E.M.), range 42-63] who served as the control group. Blood
samples were collected at 08:00, 12:00, 16:00, 20:00, 22:00,
24:00, 02:00, 04:00, 06:00, and 08:00 hours. Melatonin concentration
was measured by immunoenzymatic method. There
were significant differences in circadian melatonin profiles
as well as in the area under curve among the two studied groups.
Melatonin concentrations were significantly
lower in cancer patients in comparison with healthy individuals.
Taking into consideration stage of the
cervical cancer significantly lower melatonin secretion has
been found in all subgroups of patients in comparison with
that of tumor-free control group. Additionally, nocturnal
melatonin concentrations as well as area under curve were
significantly lower in advanced stage of cancer (stages 3
and 4) in comparison with patients with preinvasive cancer
(stage 0) at 24:00, 02:00, and 04:00 hours and patients
with stage 1 disease at 02:00 and 04:00 hours. The results
of the present study indicate that the presence of cervical
cancer influences melatonin levels in women. Moreover, stage
dependence in reduction of melatonin concentrations has been
found.
PMID: 15978060 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15926922&query_hl=4
Eur J Neurosci. 2005 May;21(10):2743-51.
Tachykinins and tachykinin-receptors
in the rat pineal gland.
Mukda S, Chetsawang B, Govitrapong
P, Schmidt PT, Hay-Schmidt A, Moller M.
Institute of Medical Anatomy, Blegdamsvej 3, DK-2200 Copenhagen,
Denmark.
High-pressure liquid chromatography of extracts of rat pineal
glands, followed by radio immunological analysis with antibodies
against tachykinins, demonstrated the presence
of substance P, neurokinin A and neurokinin B in the superficial
rat pineal gland. Immunohistochemistry on perfusion-fixed
rat brain sections showed substance P and neurokinin A to
be present in nerve fibers located both in the perivascular
spaces as well as intraparenchymally between the pinealocytes.
After extracting total RNA, followed by reverse transcription
and polymerase chain reaction amplification with primers specific
for NK1-, NK2- and NK3-receptors, agarose gel analysis of
the reaction products showed the presence of mRNA encoding
all three neurokinin receptors. Immunohistochemical analysis
showed NK1 receptor to be located in the interstitial cells
of the gland. This location was confirmed by use of in situ
hybridization using radioactively labeled antisense oligonucleotide
probes. Double immunohistochemical stainings showed that the
NK1-immunoreactive cells were not a part of the macrophages
or antigen-presenting cells of the gland. Our study suggests
that tachykinins, after release from intrapineal nerve fibers,
are involved in an up to now unknown function, different from
that of melatonin synthesis.
PMID: 15926922 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15869528&query_hl=4
Eur J Neurosci. 2005 Apr;21(8):2297-304.
The photoperiod entrains the molecular
clock of the rat pineal.
Engel L, Lorenzkowski V, Langer C,
Rohleder N, Spessert R.
Department of Anatomy, Johannes Gutenberg University, Saarstrasse
19-21, D-55099 Mainz, Germany.
The suprachiasmatic nucleus-pineal
system acts as a neuroendocrine transducer of seasonal changes
in the photoperiod by regulating melatonin formation.
In the present study, we have investigated the extent to which
the photoperiod entrains the nonself-cycling oscillator in
the Sprague-Dawley rat pineal. For this purpose, the 24-h
expression of nine clock genes (bmal1, clock, per1, per2,
per3, cry1, cry2, dec1 and dec2) and the aa-nat gene was monitored
under light-dark 8 : 16 and light-dark 16 : 8 in the rat pineal
by using real-time RT-PCR. The 24-h pattern of the expression
of only per1, dec2 and aa-nat genes was affected by photoperiod.
In comparison with the short photoperiod, the duration of
elevated expression under the long photoperiod was elongated
for per1 and shortened for dec2 and aa-nat. For each of the
genes, photoperiod-dependent variations partly persisted under
constant darkness. Therefore, the pineal
clockwork appears to memorize the photoperiod of prior entrained
cycles. The findings of the present study indicate that the
nonself-cycling oscillator of the rat pineal is entrained
by photoperiodic information and therefore that it participates
in seasonal timekeeping.
PMID: 15869528 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15945613&query_hl=4
Magnes Res. 2005 Mar;18(1):19-34.
Magnesium depletion with hypo- or hyper-
function of the biological clock may be involved in chronopathological
forms of asthma.
Durlach J, Pages N, Bac P, Bara M,
Guiet-Bara A.
SDRM, Universite Pierre et Marie Curie, 75252 Paris Cedex
05, France. jean.durlach@wanadoo.fr
Asthma is a chronic, inflammatory disorder of the airways
leading to airflow limitation. Its worldwide rise, mainly
in developed countries, is a matter of concern. Nocturnal
asthma (NA) frequently occurs and concerns two thirds of asthmatics.
But, it remains controversial whether NA is a distinct entity
or is a manifestation of more severe asthma. Generally, it
is considered as an exacerbation of the underlying pathology.
The pathological mechanisms most likely involve endogenous
circadian rhythms with pathological consequences on both respiratory
inflammation and hyperresponsiveness. A decrease in blood
and tissue magnesium levels is frequently reported in asthma
and often testifies to a true magnesium depletion. The link
with magnesium status and chronobiology are well established.
The quality of magnesium status directly
influences the Biological Clock (BC) function, represented
by the suprachiasmatic nuclei and the pineal gland.
Conversely, BC dysrythmias influence the magnesium status.
Two types of magnesium deficits must be clearly distinguished:
deficiency corresponding to an insufficient intake which can
be corrected through mere nutritional Mg supplementation and
depletion due to a dysregulation of the magnesium status which
cannot be corrected through nutritional supplementation only,
but requires the more or less specific correction of the dysregulation
mechanisms. Both in clinical and in animal experiments, the
dysregulation mechanisms of magnesium depletion associate
a reduced magnesium intake with various types of stress including
biological clock dysrhythmias. The differenciation between
Mg depletion forms with hyperfunction of BC (HBC) and forms
with hypofunction of BC (hBC) is seminal and the main biological
marker is melatonin (MT) production alteration. We hypothesize
that magnesium depletion with HBC or hBC may be involved in
chronopathological forms of asthma. Nocturnal asthma would
be linked to HBC, represented by an increase in MT levels.
The corresponding clinical forms associate diverse expressions
of nervous hypoexcitability such as depression, cluster headaches,
dyssomnia, mainly advanced sleep phase syndrome, some clinical
forms of chronic fatigue syndrome and of fibromyalgia. The
main comorbidities are depression and/or asthenia. They take
place during the night or the "bad" seasons (autumn
and winter) when sunshine is at a minimum. The corresponding
chronopathological therapy relies on bright light phototherapy
sometimes with additional psychoanaleptics. Conversely, asthma
forms linked to hBC are less frequently studied as a whole
and present a decrease in MT levels. They associate various
signs of nervous hyperexcitability such as anxiety, diurnal
cephalalgia (mainly migraine), dyssomnia, mainly delayed sleep
phase syndrome, and some clinical forms of chronic fatigue
syndrome and of fibromyalgia. The treatment relies on diverse
forms of "darkness therapy", possibly with the help
of some psycholeptics. Finally, the treatment of asthma involves
the maintenance of a standard dosing schedule of anti-asthma
drugs, a balanced magnesium intake and the appropriate treatment
of the chronopathological disorders.
PMID: 15945613 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15816940
Epilepsia. 2005 Apr;46(4):473-80.
Hippocampal melatonin receptors modulate
seizure threshold.
Stewart LS, Leung LS.
Program in Neuroscience, Department of Physiology & Pharmacology,
The University of Western Ontario, London, Ontario, Canada.
lee.stewart@mcgill.ca
PURPOSE: The pineal hormone melatonin has been shown to enhance
hippocampal excitability. We therefore investigated whether
inactivation of hippocampal melatonin receptors affects behavioral
seizures.
METHODS: Intrahippocampal infusions were performed in rats
to study the effect of different melatonin receptor antagonists
on behavioral activity, EEG, and seizure susceptibility. Experiments
were conducted at 2 times of the day that coincided with the
peak and trough of the daily melatonin rhythm.
RESULTS: Local infusion of the Mel(1b) receptor antagonist
4-phenyl-2-propionamidotetralin (4-P-PDOT) into the hippocampus,
but not the overlying neocortex, significantly increased seizure
latency and in some cases provided complete protection against
seizure development. In addition, 4-P-PDOT suppressed open
field activity and hippocampal EEG amplitude. The mixed Mel(1a)/Mel(1b)
receptor antagonist luzindole also increased seizure latency
but to a lesser degree than 4-P-PDOT. The behavioral effects
of Mel(1b) receptor inhibition were comparable to those of
the gamma-aminobutyric acid (GABA)(A) receptor agonist muscimol
and were observed during the dark phase (2400-0200 h) but
not the light phase (1200-1400 h) of the daily photocycle.
The anticonvulsant effect of intrahippocampal infusion of
4P-P-DOT was blocked by coadministration of the GABA(A) antagonist
bicuculline.
CONCLUSIONS: Our results suggest that
nocturnal activation of hippocampal Mel(1b) receptors depresses
GABA(A) receptor function in the hippocampus and enhances
seizure susceptibility.
PMID: 15816940 [PubMed - in process]
From
Science Direct
Journal of Neuroimmunology - Volume 161, Issues 1-2 , April
2005, Pages 137-144
Time course and role of the pineal
gland in photoperiod control of innate immune cell functions
in male Siberian hamsters
Steven M. Yellon (a, b), Kiam Kim (a),
Allison R. Hadley (a) and Long T. Tran (a)
(a)Center for Perinatal Biology Research, Department of Physiology,
School of Medicine, Loma Linda University Adventist Health
Sciences Center, USA
( b) Immunology Research Group, Loma Linda University Adventist
Health Sciences Center, Loma Linda, CA, USA
The time course of select phagocyte and natural killer activities
to short days was determined. In advance of testes regression,
circulating granulocyte and monocyte cell numbers in hamsters
decreased while lymphocyte numbers increased; phagocytosis
and oxidative burst activity also decreased. To determine
whether the pineal gland influences these innate immune cell
functions, hamsters were exposed to constant light. Photoperiod
control of testes weight and basal oxidative burst activity
was abolished by treatment with constant light; other phagocyte
activities and leukocyte proportions in circulation were not
affected. The findings suggest that
photoperiod and pineal gland function may regulate certain
innate immune activities.
From
Science Direct
Sleep Medicine
Reviews Volume 9, Issue 1 , February 2005,
Pages 11-24
Physiological review
The
basic physiology and pathophysiology of melatonin
Bruno Claustrat
(a), Jocelyne Brun (a) and Guy Chazot (b)
(a) Centre de Médecine
Nucléaire, Service de Radioanalyse, Hôpital Neuro-Cardiologique,
59 Boulevard Pinel, 69394 Lyon Cedex 03, France
(b) Service de Neurologie, Hôpital Neuro-Cardiologique,
Lyon, France
Summary. Melatonin
is a methoxyindole synthesized and secreted principally by
the pineal gland at night under normal environmental conditions.
The endogenous rhythm of secretion is generated by the suprachiasmatic
nuclei and entrained to the light/dark cycle. Light is able
to either suppress or synchronize melatonin production according
to the light schedule. The nycthohemeral rhythm of this hormone
can be determined by repeated measurement of plasma or saliva
melatonin or urine sulfatoxymelatonin, the main hepatic metabolite.
The primary physiological
function of melatonin, whose secretion adjusts to night length,
is to convey information concerning the daily cycle of light
and darkness to body physiology. This information is used
for the organisation of functions, which respond to changes
in the photoperiod such as the seasonal rhythms. Seasonal
rhythmicity of physiological functions in humans related to
possible alteration of the melatonin message remains, however,
of limited evidence in temperate areas in field conditions.
Also, the daily melatonin secretion, which is a very robust
biochemical signal of night, can be used for the organisation
of circadian rhythms. Although functions of this hormone in
humans are mainly based on correlative observations, there
is some evidence that melatonin stabilises and strengthens
coupling of circadian rhythms, especially of core temperature
and sleep-wake rhythms. The circadian organisation of other
physiological functions could depend on the melatonin signal,
for instance immune, antioxidative defences, hemostasis and
glucose regulation.
Since the regulating
system of melatonin secretion is complex, following central
and autonomic pathways, there are many pathophysiological
situations where the melatonin secretion can be disturbed.
The resulting alteration could increase
predisposition to disease, add to the severity of symptoms
or modify the course and outcome of the disorder.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15652871
Biol Psychiatry.
2005 Jan 15;57(2):134-8.
Nocturnal excretion of 6-sulphatoxymelatonin
in children and adolescents with autistic disorder.
Tordjman
S, Anderson GM, Pichard N, Charbuy H, Touitou Y.
Center for Scientific
Research, Unite de Recherche Mixte 7593, Vurnerabilite, Adaptation
et Psychopathologie, Hopital Pitie-Salpetriere, Centre Hospitalier
Guillaume Regnier, Faculte de Medecine Universite de Rennes
1.
BACKGROUND: Many
studies in autistic disorder report sleep problems and altered
circadian rhythms, suggesting abnormalities in melatonin physiology.
Additionally, melatonin, a pineal gland hormone produced from
serotonin, is of special interest in autistic disorder given
reported alterations in central and peripheral serotonin neurobiology.
METHODS: Nocturnal urinary excretion of 6-sulphatoxymelatonin
was measured by radioimmunoassay in groups of children and
adolescents with autistic disorder (n = 49) and normal control
individuals (n = 88) matched on age, sex, and Tanner stage
of puberty.
RESULTS: Nocturnal 6-sulphatoxymelatonin excretion rate was
significantly and substantially lower in patients with autism
than in normal controls (mean +/- SEM, .75 +/- .11 vs. 1.80
+/- .17 mug/hr, p =.0001), and was significantly negatively
correlated with severity of autistic impairments in verbal
communication and play (p < .05).
CONCLUSIONS: These findings indicate
clearly that nocturnal production of melatonin is reduced
in autism. Further research is warranted in order to
understand the mechanisms underlying the lower melatonin production,
to assess the impact of altered melatonin on the pathophysiology
and behavioral expression of autistic disorder, and to determine
the utility of melatonin administration in individuals with
autism.
PMID:
15652871 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15666035
J Neural Transm.
2005 Jan 24; [Epub ahead of print]
Antioxidant capacity of the neurohormone
melatonin.
Sofic
E, Rimpapa Z, Kundurovic Z, Sapcanin A, Tahirovic I, Rustembegovic
A, Cao G.
Neuroscience and
Phytochemical Laboratories, Jean Mayer USDA Human Nutrition
Research Center on Aging, Tuft-s University, and Department
of Molecular and Cellular Toxicology, HSPH, Harvard University,
Boston, MA, U.S.A..
The aim of this
study was to elucidate the antioxidant behaviour of melatonin
(M) and determine its activity-structure relationship.
M or 5-metoxy-N acetyltriptamine is a neurohormone secreted
by the pineal gland, which plays a proven role in maintaining
sleep-wake rhythms. The antioxidant capacity of M was analysed
using the oxygen radical absorbance capacity (ORAC) assay.
Furthermore, spectral measurements for aerobic photolytic
reaction of neutral red (NR) and degree of inhibition of photolysis
with M, glutathione (GSH), ascorbic acid (AA) and vitamin
E analogue Trolox were studied at room temperature 25 degrees
C, using visible (VIS) and ultra-violet (UV) radiations. In
the ORAC assay 2,2-azobis (2-amidino-propane)dihydrochloride
(AAPH) a peroxyl radical generator, ROO degrees ; H(2)O(2)-Cu(2+),
mainly a hydroxyl radical generator, degrees OH; and Cu(2+)
a transition metal were used. Although some studies indicated
that M is a powerful antioxidant, no one has compared its
antioxidant capacities with GSH, E-vitamin and AA, using three
free radical (FR) generators in an assay which utilizes an
area-under curve technique and thus combines both inhibition
time and inhibition degree of FR action by an antioxidant
into a single quantity. In the current study, we used ORAC
assay with three FR generators. The assay is based on propensity
of the fluorescence emitted by the protein beta-phycoerythrin
(beta-PE) from porphyridium cruentum to be quenched when exposed
to FR action. M in our experiments acted as a universal antioxidant
against ROO degrees and degrees OH radicals. Also, M served
as an antioxidant in the presence of Cu(2+). M, which is a
lipid-soluble compound, was a twice more powerful antioxidant
than vitamin E, and four times than AA or GSH. Furthermore,
M inhibited aerobic photolysis of NR photoinduced with VIS
and UV rays faster and more effectively, than AA, GSH or vitamin
E. AA with NR, under aerobic conditions during irradiation
with VIS and UV acted as a pro-oxidant.M
may be the premier molecule to protect the cells from oxidative
stress.
PMID:
15666035 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15621008
Brain Res. 2005
Jan 7;1031(1):10-9.
Melatonin modulates intercellular communication
among cultured chick astrocytes.
Peters
JL, Cassone VM, Zoran MJ.
Department of Biology
and Center for Biological Clocks Research, Texas A&M University,
Room 231, College Station, TX 77843-3258, USA.
Melatonin, a pineal
neurohormone, mediates circadian and seasonal processes in
birds and mammals. Diencephalic astrocytes are sites of action,
at least in birds, since they express melatonin receptors
and melatonin affects their metabolism. We tested whether
astrocytic calcium waves are also modulated by melatonin.
Calcium waves, which we found to be regulated in cultured
chick glial cells by an IP(3)-dependent mechanism, were potentiated
by physiological concentrations of melatonin. Melatonin also
increased resting calcium levels and reduced gap junctional
coupling among astrocytes, at concentrations that facilitated
calcium waves. These modulatory effects were diminished by
melatonin receptor blockade and pertussis toxin (PTX). Thus,
melatonin induced a functional shift in the mode of intercellular
communication, between junctional coupling and calcium waves,
among glial cells. We suggest a mechanism where neuroglial
physiology, involving GTP-binding protein signaling pathways,
links rhythmic circadian outputs to pervasive neurobehavioral
states.
PMID:
15621008 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15649735
Sleep Med Rev.
2005 Feb;9(1):11-24.
The basic physiology and pathophysiology
of melatonin.
Claustrat
B, Brun J, Chazot G.
Centre de Medecine
Nucleaire, Service de Radioanalyse, Hopital Neuro-Cardiologique,
59 Boulevard Pinel, 69394 Lyon Cedex 03, France.
Melatonin is a
methoxyindole synthesized and secreted principally by the
pineal gland at night under normal environmental conditions.
The endogenous rhythm of secretion is generated by the suprachiasmatic
nuclei and entrained to the light/dark cycle. Light is able
to either suppress or synchronize melatonin production according
to the light schedule. The nycthohemeral rhythm of this hormone
can be determined by repeated measurement of plasma or saliva
melatonin or urine sulfatoxymelatonin, the main hepatic metabolite.
The primary physiological function of melatonin, whose secretion
adjusts to night length, is to convey information concerning
the daily cycle of light and darkness to body physiology.
This information is used for the organisation of functions,
which respond to changes in the photoperiod such as the seasonal
rhythms. Seasonal rhythmicity of physiological functions in
humans related to possible alteration of the melatonin message
remains, however, of limited evidence in temperate areas in
field conditions. Also, the daily melatonin secretion, which
is a very robust biochemical signal of night, can be used
for the organisation of circadian rhythms. Although functions
of this hormone in humans are mainly based on correlative
observations, there is some evidence that melatonin stabilises
and strengthens coupling of circadian rhythms, especially
of core temperature and sleep-wake rhythms. The circadian
organisation of other physiological functions could depend
on the melatonin signal, for instance immune, antioxidative
defences, hemostasis and glucose regulation. Since
the regulating system of melatonin secretion is complex, following
central and autonomic pathways, there are many pathophysiological
situations where the melatonin secretion can be disturbed.
The resulting alteration could increase predisposition to
disease, add to the severity of symptoms or modify the course
and outcome of the disorder.
PMID:
15649735 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15683466
J Pineal Res. 2005
Mar;38(2):116-22.
Demonstration of PACAP-immunoreactive
intrapineal nerve fibers in the golden hamster (Mesocricetus
auratus) originating from the trigeminal ganglion.
Baeres
FM, Moller M.
Institute of Medical
Anatomy, Panum Institute, University of Copenhagen, Copenhagen,
Denmark.
By using immunohistochemistry,
a network of nerve fibers containing pituitary adenylate-cyclase
activating polypeptide (PACAP) was demonstrated in the pineal
gland of the golden hamster, a photoperiodic species
often used in pineal and circadian rhythm research. The nerve
fibers are present in the capsule from where they permeate
into the pineal perivascular spaces and parenchyma. Immuno-electron
microscopy showed the PACAPergic nerve terminals, with clear
transmitter vesicles, to terminate in the interstitial spaces
between the pinealocytes or in the perivascular spaces. Some
of the PACAPergic nerve terminals made synapse-like contacts
with the pinealocytes. The origin of the PACAP-containing
nerve fibers innervating the pineal gland of the hamster was
investigated by combined retrograde tracing with fluorogold
and immunohistochemistry for PACAP. A 2% fluorogold solution
was injected iontophoretically into the superficial pineal
gland and the animals were allowed to survive for 1 wk. After
perfusion fixation of the rats, the location of the tracer
was investigated in the brain, the parasympathetic sphenopalatine,
and otic ganglia, as well as in the sensory trigeminal ganglia.
The tracer was found in perikarya of
all the investigated ganglia. However, co-localization
with PACAP was found only in the trigeminal ganglion.
PMID:
15683466 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15683461
J Pineal Res. 2005
Mar;38(2):73-83.
Melatonin
as an organoprotector in the stomach and the pancreas.
Jaworek
J, Brzozowski T, Konturek SJ.
Department of Physiology,
Jagiellonian University College of Medicine, Cracow, Poland.
Melatonin was thought
to originate primarily from the pineal gland and to be secreted
during the night, but recent studies
revealed that gastrointestinal (GI) tract presents another,
many times larger, source of melatonin that contributes significantly
to the circulating concentration of this indole. Melatonin
may exert a direct effect on GI tissues but its major influence
on GI organs seems to occur indirectly, via the brain-gut
axis including peripheral receptors, sensory afferent (vagal
or sympathetic) pathways and central nervous system (CNS)
acting on these organs via autonomic efferents and neuromediators.
This article reviews and updates our experience with
the fascinating molecule, as related to GI organs, with special
focus on secretory activity of the stomach and pancreas and
the maintenance of their tissue integrity. In addition to
being released into the circulation, melatonin is also discharged
into the gut lumen and this appears to be implicated in the
postprandial stimulation of pancreatic enzyme secretion, mediated
by melatonin-induced release of cholecystokinin, acting through
entero-gastro-pancreatic reflexes. Although exerting certain
differences in the mechanism of action on gastric and pancreatic
secretory activities, melatonin derived from its precursor
l-tryptophan, exhibits similar highly protective actions against
the damage of both the stomach and the pancreas and accelerates
the healing of chronic gastric ulcerations by stimulating
the microcirculation and cooperating with arachidonate metabolites
such as prostaglandins, with nitric oxide released from vascular
endothelium, and/or sensory nerves and with their neuropeptides
such as calcitonin gene related peptide. The beneficial effects
of melatonin results in gastro- and pancreato-protection,
prevents various forms of gastritis and pancreatitis through
the activation of specific MT(2)-receptors and scavenges reactive
oxygen species (ROS). Melatonin counteracts the increase in
the ROS-induced lipid peroxidation and preserves, at least
in part, the activity of key anti-oxidizing enzymes such as
superoxide dismutase. It is proposed
that melatonin should be considered as the agent exerting
an important role in prevention of gastric and pancreatic
damage and in accelerating healing of gastric ulcers.
PMID:
15683461 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15589043
J Neuroimmunol.
2005 Jan;158(1-2):106-11.
Does
melatonin play a disease-promoting role in rheumatoid arthritis?
Maestroni
GJ, Cardinali DP, Esquifino AI, Pandi-Perumal SR.
Center for Experimental
Pathology, Cantonal Institute of Pathology, Via In Selva 24,
P.O. Box 6601 Locarno, Switzerland.
The pineal neurohormone
melatonin (MLT) has been widely shown to exert an immunostimulatory
and antiapoptotic role, mainly by acting on Th cells and on
T and B cell precursors, respectively. Thus, MLT might favor
or promote autoimmune diseases by acting directly on immature
and mature immunocompetent cells. In fact, preclinical and
clinical evidence point to a disease-promoting role of MLT
in rheumatoid arthritis (RA). MLT, whose concentration is
increased in serum from RA patients, may act systemically
or locally in the inflamed joints. The circadian secretion
of MLT with a peak level during the night hours might be strictly
correlated with the peculiar daily rhythmicity of the RA symptoms.
In rat studies employing Freund's complete mycobacterial adjuvant
(FCA) as a model of rheumatoid arthritis, pinealectomized
rats turned arthritic and exhibited a significantly less pronounced
inflammatory response, which was restored to normal by a low
MLT dose and was aggravated by a pharmacological MLT dose,
that augmented the inflammatory and immune response. Continued
investigation will refine our understanding of these observations,
which will possibly translate into improved therapeutic approaches.
PMID:
15589043 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15607834
Brain Res Bull.
2005 Jan 15;64(5):455-61.
Attenuation
of gonadal response to photostimulation following ablation
of neurons in the lateral septal organ of chicks.
Rathinam
T, Kuenzel WJ.
Poultry Science
Center, 1260 W Maple St, University of Arkansas, Fayetteville,
AR 72701, USA.
Many avian species
in temperate zones respond to long photoperiods by showing
recrudescence of gonads. Compelling evidence show that non-retinal,
non-pineal photoreceptors exist in the avian brain. Within
the ventral forebrain are specialized neurons that respond
to light found in the medial portion of a circumventricular
organ called the lateral septal organ
(LSO). The objective of this study was to examine whether
the integrity of the LSO was critical for rapid gonadal development
in young male chicks placed under long day photostimulation.
Birds were initially kept on a short photoperiod (LD 8:16)
until 2 weeks of age, at which time bilateral electrolytic
lesions were administered to the LSO. After surgery, birds
were transferred to a long photoperiod (LD 16:8) and fed a
chick starter diet containing 0.2% sulfamethazine (SMZ). The
combination of a long day plus SMZ is known to stimulate sexual
maturation in male chicks. In four separate experiments conducted
to date, bilateral lesions directed to the LSO and lesions
that missed and were placed caudal and ventral to the target
resulted in a significant decrease in testes weight, compared
to sham-operated controls (P<0.05). Results
suggest that neurons in the LSO may be directly involved in
responding to long photoperiods and stimulating gonadal development
in broiler chicks.
PMID:
15607834 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15607825
Brain Res Bull.
2005 Jan 15;64(5):371-380.
Role of the pineal gland and melatonin
in the photoperiodic control of hypothalamic gonadotropin-releasing
hormone in the male jerboa (Jaculus orientalis), a desert
rodent.
El
Qandil S, Chakir J, El Moussaouiti R, Oukouchoud R, Rami N,
Benjelloun WA, Lakhdar-Ghazal N.
Department de Biologie,
Unite de Neurosciences, Faculte des Sciences, Groupe de Recherche
sur les Rythmes Biologiques, Universite Mohammed V, BP. 1014,
avenue Ibn Battouta 10000 Rabat, Morocco; Laboratoire de Physiologie
Animale, Faculte des Sciences, Universite Hassan II-Mohammedia,
Casablanca, Morocco.
The neuroendocrine
mechanism underlying seasonal changes in gonadal activity
of the jerboa, a desert hibernating rodent adapted to harsh
climatic conditions, are poorly understood. We investigated
the role of the pineal gland and melatonin in the photoperiodic
control of hypothalamic gonadotropin-releasing hormone (GnRH).
Intact and pinealectomized male jerboas were subjected to
short photoperiod, while others were kept under long photoperiod
and injected daily with melatonin or vehicle. Testes activity
was monitored by evaluating the testes volume during 10 weeks.
GnRH immunoreactivity was investigated quantitatively with
image analysis. Following melatonin administration, the hormone
peaked in plasma after 30min, with return to control levels
2.5h later. Exposure to short photoperiod and melatonin resulted
in marked increase in the number of GnRH-containing cells
in the preoptic area and mediobasal hypothalamus, whereas
GnRH immunoreactivity of fibers and terminals in the median
eminence decreased under these conditions. The findings indicate
that in the jerboa short photoperiod induces testicular regression
by prolonging the duration of melatonin as an endocrine signal.
This mechanism probably involves inhibition of GnRH release
in the median eminence, with consequent accumulation of GnRH
in perikarya of the preoptic area and mediobasal hypothalamus.
Interestingly, GnRH cells of the median eminence did not appear
to be influenced by the photoperiod and pineal melatonin,
whereas their number was increased by exogenous melatonin.
The latter data suggest for the first time the involvement
of an extrapineal melatonin, whose origin remains to be identified,
in the modulation of the GnRH regulatory system in rodents.
PMID:
15607825 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15606905
J Neurochem. 2005
Jan;92(1):158-70.
Molecular cloning, localization and
circadian expression of chicken melanopsin (Opn4): differential
regulation of expression in pineal and retinal cell types.
Chaurasia
SS, Rollag MD, Jiang G, Hayes WP, Haque R, Natesan A, Zatz
M, Tosini G, Liu C, Korf HW, Iuvone PM, Provencio I.
Department of Pharmacology,
Emory University School of Medicine, Atlanta, Georgia, USA.
The avian retina
and pineal gland contain autonomous circadian oscillators
and photo-entrainment pathways, but the photopigment(s) that
mediate entrainment have not been definitively identified.
Melanopsin (Opn4) is a novel opsin involved in entrainment
of circadian rhythms in mammals. Here, we report the cDNA
cloning of chicken melanopsin and show its expression in retina,
brain and pineal gland. Like the melanopsins identified in
amphibians and mammals, chicken melanopsin is more similar
to the invertebrate retinaldehyde-based photopigments than
the retinaldehyde-based photopigments typically found in vertebrates.
In retina, melanopsin mRNA is expressed in cells of all retinal
layers. In pineal gland, expression was strong throughout
the parenchyma of the gland. In brain, expression was observed
in a few discrete nuclei, including the lateral septal area
and medial preoptic nucleus. The retina and pineal gland showed
distinct diurnal expression patterns. In pineal gland, melanopsin
mRNA levels were highest at night at Zeitgeber time (ZT) 16.
In contrast, transcript levels in the whole retina reached
their highest levels in the early morning (ZT 0-4). Further
analysis of melanopsin mRNA expression in retinal layers isolated
by laser capture microdissection revealed different patterns
in different layers. There was diurnal expression in all retinal
layers except the ganglion cell layer, where heavy expression
was localized to a small number of cells. Expression of melanopsin
mRNA peaked during the daytime in the retinal pigment epithelium
and inner nuclear layer but, like in the pineal, at night
in the photoreceptors. Localization and regulation of melanopsin
mRNA in the retina and pineal gland is consistent with the
hypothesis that this novel photopigment plays a role in photic
regulation of circadian function in these tissues.
PMID:
15606905 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15617533
J Pineal Res. 2005
Jan;38(1):17-26.
Reactive changes of interstitial glia
and pinealocytes in the rat pineal gland challenged with cell
wall components from gram-positive and -negative bacteria.
Jiang-Shieh
YF, Wu CH, Chien HF, Wei IH, Chang ML, Shieh JY, Wen CY.
Department of Anatomy,
College of Medicine, National Cheng Kung University, Tainan.
Lipopolysaccharide
(LPS), the major proinflammatory component of gram-negative
bacteria, is well known to induce sepsis and microglial activation
in the CNS. On the contrary, the effect of products from gram-positive
bacteria especially in areas devoid of blood-brain barrier
remains to be explored. In the present study, a panel of antibodies,
namely, OX-6, OX-42 and ED-1 was used to study the response
of microglia/macrophages in the pineal gland of rats given
an intravenous LPS or lipoteichoic acid (LTA). These antibodies
recognize MHC class II antigens, complement type 3 receptors
and unknown lysosomal proteins in macrophages, respectively.
In rats given LPS (50 mug/kg) injection and killed 48 h later,
the cell density and immunoexpression of OX-6, OX-42 and ED-1
in pineal microglia/macrophages were markedly increased. In
rats receiving a high dose (20 mg/kg) of LTA, OX-42 and OX-6,
immunoreactivities in pineal microglia/macrophages were also
enhanced, but that of ED-1 was not. In addition, both bacterial
toxins induced an increase in astrocytic profiles labelled
by glial fibrillary acid protein. An interesting feature following
LPS or LTA treatment was the lowering effect on serum melatonin,
enhanced serotonin immunolabelling and
cellular vacuolation as studied by electron microscopy
in pinealocytes. The LPS- or LTA-induced vacuoles appeared
to originate from the granular endoplasmic reticulum as well
as the Golgi saccules. The present results suggest that LPS
and LTA could induce immune responses of microglia/macrophages
and astroglial activation in the pineal gland. Furthermore,
the metabolic and secretory activity of pinealocytes was modified
by products from both gram-positive and -negative bacteria.
PMID:
15617533 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15544844
Regul Pept. 2005
Jan 15;124(1-3):81-7.
Expression of orexin receptors in the brain and peripheral
tissues of the male sheep.
