Biomedical subjects

D P Cardinali

Publications and source records attributed to D P Cardinali.

At least 55 records · Page 3Linked to original sources

PubMed1998

Diurnal rhythms in norepinephrine and acetylcholine synthesis of sympathetic ganglia, heart and adrenals of aging rats: effect of melatonin.

The effect of aging and melatonin on 24-h rhythms in tyrosine hydroxylase activity and 3H - choline conversion into 3H - acetylcholine were examined in cervical, stellate, coeliac-mesenteric and hypogastric ganglia, and in the adrenal medulla and heart of rats. Young (50 days old) and old (18 months old) rats received evening injections of 10 or 100 microg of melatonin or its vehicle for 17 days. In superior cervical, stellate and coeliac-superior mesenteric ganglia, as well as in the adrenal medulla, norepinephrine and acetylcholine synthesis attained maximal values at night (c.a. 2030-0100 h). In the hypogastric ganglion, maximal tyrosine hydroxylase activity occurred at night at both studied ages. Two maxima in acetylcholine synthesis were detected in hypogastric ganglion of young rats (c.a. 1300 h and 0100 h, respectively) while in old rats a single maximum was observed at noon. Cardiac tyrosine hydroxylase activity peaked at early night (c.a. 2200-2300 h) while cardiac acetylcholine synthesis peaked at the afternoon (c.a. 1700-1900 h). Old rats exhibited a significant decrease of rhythm amplitude and increase of mean values in tyrosine hydroxylase activity in autonomic ganglia and adrenal medulla, and abolition of tyrosine hydroxylase rhythm in the heart. Twenty-four hour rhythmicity in acetylcholine synthesis was impaired or abolished in aged rats. Treatment of old rats with 10 or 100 microg melatonin generally augmented amplitude of rhythms and reinduced the nocturnal peak of acetylcholine synthesis in the hypogastric ganglion. Only the high melatonin dose significantly augmented rhythm amplitude of tyrosine hydroxylase activity (superior cervical and coeliac-superior mesenteric ganglia) and acetylcholine synthesis (superior cervical, stellate and coeliac-superior mesenteric ganglia) in young rats. The results indicate that the activity of the central oscillator, driven to the organs in part via the autonomic nervous system, deteriorates significantly with aging and that melatonin may restore partially such a deterioration.

Acetylcholine↗

PubMed1998

Neonatal clomipramine treatment of Syrian hamsters: effect on the circadian system.

The circadian behavior of male Syrian hamsters injected with the serotonin/norepinephrine reuptake inhibitor clomipramine (15 mg/kg from postnatal days 8 to 21) was examined. Clomipramine treatment significantly augmented mean activity values of wheel running rhythm, as well as delayed its acrophase. After a 6-h phase advance of the light-dark cycle, reentrainment of clomipramine-treated hamsters took significantly longer than controls. Clomipramine-treated hamsters exhibited a shorter circadian period than controls in constant light conditions, but no differences were found in constant darkness. Light pulses applied at late subjective night to clomipramine-treated hamsters caused significantly reduced phase advances as compared to controls, while no differences were found in phase delay magnitudes when light pulses were applied during early subjective night. Administration of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) at circadian time 8 significantly advanced the onset of activity to a greater extent in clomipramine-treated hamsters than in controls. The results indicate that neonatal clomipramine treatment of hamsters causes long-lasting changes in the circadian system, by increasing activity levels and by partially inhibiting light-evoked responses. An enhancement of a non-photic, serotonergic-induced response was also unveiled.

Animals↗

PubMed1998

Diurnal rhythms in ornithine decarboxylase activity and norepinephrine and acetylcholine synthesis in submaxillary lymph nodes and spleen of young and aged rats during Freund's adjuvant-induced arthritis.

Aging has been associated with attenuation of amplitude and changes in period of many circadian rhythms. The present study was carried out to examine, in young (50 days old) and old (18 months old) rats, whether 24-h rhythms of cell proliferation (as assessed by measuring ornithine decarboxylase activity) and of presynaptic adrenergic and cholinergic markers change in lymph nodes and spleen during Freund's adjuvant-induced arthritis. Groups of young and old Sprague-Dawley rats were studied the day before, and on days 6, 12 and 18 after Freund's adjuvant injection. On day 16 after adjuvant injection, inflammation of hind paws, mainly in the ankle joints, was less marked in old than in young rats. Lymph node and splenic ornithine decarboxylase activity exhibited significant 24-h variations with maximal activity during daily hours. Before treatment, enzyme activity values were significantly lower in old rats in both tissues examined. During the immune reaction, lymph node and splenic ornithine decarboxylase augmented 8-10-fold, with progressively smaller amplitude of daily variations as arthritis developed. In every case, mesor and amplitude of ornithine decarboxylase activity were lowest in old rats. Submaxillary lymph node and splenic tyrosine hydroxylase activity attained maximal values at night. At every time interval after mycobacterium adjuvant injection, amplitude and mesor of tyrosine hydroxylase activity rhythm were lowest in old rats. A maximum in submaxillary lymph node 3H-acetylcholine synthesis occurred at the afternoon. On day 6 and 12 after Freund's adjuvant injection, lymph node 3H-acetylcholine synthesis was significantly smaller in old rats. Day-night differences in submaxillary lymph node or splenic ornithine decarboxylase and tyrosine hydroxylase activities, or in submaxillary lymph node 3H-acetylcholine synthesis, of rats treated with the adjuvant's vehicle, did not differ significantly from those seen in untreated controls. The results are compatible with an age-dependent decline of immune-mediated inflammatory responses. The activity of the central circadian oscillator, driven to the organs in part via the autonomic nervous system, seems also to deteriorate during aging.

Acetylcholine↗

PubMed1998

Effect of superior cervical ganglionectomy on catecholamine concentration in rat cochlea.

Both noradrenergic and dopaminergic nerve terminals have been described in the cochlea. The present report focused on the effect of superior cervical ganglionectomy (SCGx) on monoamine concentration in adult rat cochlea. In homogenates of whole cochleas, we measured the concentrations of norepinephrine (NE), dopamine (DA) and its main metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), by HPLC coupled to electrochemical detection. Measurements were carried out 4 h, 24 h or 6 days after unilateral SCGx. Most of the NE (approximately 82%) was lost after sympathectomy on the ipsilateral side, indicating that the principal localization of cochlear NE is in peripheral sympathetic fibers. Since about 18% of NE remained detectable 6 days after SCGx, a second origin of cochlear noradrenergic fibers may exist. Cochlear concentrations of DA or its metabolites did not change after SCGx. Therefore, DA and NE are located in two different populations of fibers within the cochlea, and are presumably related to distinct functional roles.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1998

Basic aspects of melatonin action.

Melatonin is synthesized and secreted during the dark period of the light-dark cycle. Thus, melatonin has an obvious association with sleep, at least in diurnal animals. Rhythmic nocturnal melatonin secretion is directly generated by the circadian clock, located in mammals within the suprachiasmatic nuclei (SCN), and is entrained to a 24-h period by the light-dark cycle. The periodic secretion of melatonin may be used as a circadian mediator to any system than can "read" the message. In addition, direct effects of the hormone on the SCN could explain some of melatonin effects on the circadian system. Duration of melatonin nocturnal secretion is directly proportional to the length of the night and it has been demonstrated experimentally to be the critical parameter for photoperiod integration. The two main hypotheses to explain the action of melatonin are the duration hypothesis (supporting that night length is coded by the duration of the melatonin secretory phase) and the coincidence hypothesis (holding that physiological responses are linked to the existence of a diurnal rhythm in sensitivity to melatonin). The sites and mechanisms of action of melatonin for circadian and photoperiodic responses are far from being elucidated, but action through specific membrane receptor sites is well documented. In view of melatonin s lipophilic nature, interactions with specific intracellular proteins like calmodulin or tubulin, or with nuclear receptor sites, have also been considered, whereas the physiological significance of the documented antioxidant effect of melatonin remains to be settled. Melatonin seems to act as an "arm" of the circadian clock, giving a time-related signal to a number of body functions; one of these, the circadian organization of an organism's defence, is discussed in some detail as an example.

Journal Article↗

PubMed1998

The rhythmic GABAergic system.

GABA is the major inhibitory neurotransmitter in the mammalian brain, and has been implicated in the regulation of a variety of behavioral functions, including biological rhythms. The focus of this minireview is the rhythmic variation of the central GABAergic system, comprising fluctuations of GABA levels and turnover, GABA receptor affinity and postsynaptic activity on the chloride ionophore in rodent's brain. Neurochemical rhythms correlated with diurnal and circadian changes in several behaviors associated with the GABA(A) receptor, e.g., anxiolysis-related behavior. GABA is considered to be the principal neurotransmitter of the mammalian circadian system, being present in the suprachiasmatic nuclei and the intergeniculate leaflet. Pharmacological manipulations of GABA(A) receptors phase shift circadian rhythms and alter circadian responses to light. Administration of putative modulators of GABA function, like melatonin or neuroactive steroids, affects the timing of biological rhythms. Therefore, not only does the GABAergic system exhibit strong diurnal and circadian variations, but it also serves as one of the key modulators of the circadian apparatus.

Animals↗

PubMed1998

Monozygotic twins with Alzheimer's disease treated with melatonin: Case report.

Monozygotic twins with Alzheimer's disease of 8 years duration were studied. The onset of the disease differed by about 6 months between twins and was characterized by a primary impairment of memory function. Clinical evaluation at the time of diagnosis indicated a similar cognitive and neuroimaging alteration in both patients, as well as a similar neuropsychologic impairment. A possible genetic origin of the disease was suggested by a similar disease suffered by the mother. Patients were initially treated with vitamin E (800 I.U./day). Starting at approximately the same time (about 3 years ago), they received 50 mg/day thioridazine because of the behavioral and sleep disorder. One of the patients was treated with melatonin (6 mg orally) at bed time daily for 36 months. Evolution of the disease in the melatonin-treated patient indicated a milder impairment of memory function, with substantial improvement of sleep quality and reduction of sundowning. This led to discontinuance (after 3 months) of thioridazine treatment. Present clinical evaluation indicated a difference in functional stage of the disease between the twins (Functional Assessment Tool For Alzheimer's Disease, FAST), with a score of 5 in the twin who received melatonin and of 7b in the twin who did not receive it. Since experimental data on melatonin in animals indicated its antioxidant, antiapoptotic, and beta-amyloid-decreasing activity, the hypothesis that melatonin has a beneficial effect in Alzheimer's disease patients should be considered.

Aged↗

PubMed1998

Effect of melatonin on 24-hour rhythms of ornithine decarboxylase activity and norepinephrine and acetylcholine synthesis in submaxillary lymph nodes and spleen of young and aged rats.

Young (50 days old) and old (18 months old) Sprague-Dawley rats were injected with mycobacterial Freund's adjuvant to produce an inflammatory disease of the joints and were studied the day before, and on days 6, 12 and 18 after injection. At every postinjection interval examined, old rats had significantly lower circadian amplitudes of pineal melatonin content. On day 18 of arthritis development, decreased levels of pineal melatonin were also seen in young rats. A second study, carried out 18 days after the injection of Freund's complete adjuvant and after 17 daily injections of 10 or 100 microg of melatonin in the evening, indicated that melatonin treatment restored the inflammatory response in old rats (assessed plethysmographically in hind paws) to the level found in young animals. In young rats, an inflammation-promoting effect of 100 microg melatonin could be demonstrated. As a consequence of the immune reaction, submaxillary lymph node and splenic ornithine decarboxylase activity (an index of lymph cell proliferation) augmented significantly, with acrophases of 24-hour rhythms in the afternoon for lymph nodes or in the morning for spleen. Mesor and amplitude of ornithine decarboxylase rhythm were lowest in old rats, while melatonin injection generally augmented its amplitude. Lymph node and splenic tyrosine hydroxylase activity (a presynaptic adrenergic marker) reached maximal values during early night hours while maximal values of [3H]acetylcholine synthesis (a presynaptic cholinergic marker) occurred during the afternoon in lymph nodes. Amplitude and mesor of these rhythms were lowest in old rats, an effect generally counteracted by melatonin treatment. The results suggest that inflammation is accompanied by an age-dependent, significant depression of pineal melatonin synthesis during adjuvant-induced arthritis and a decreased amplitude of the circadian rhythm of immune cell proliferation and autonomic activity in lymph nodes and spleen. These effects are counteracted by injection of melatonin, mainly in old rats.

Acetylcholine↗

PubMed1998

Development of 24-hour rhythms in serum prolactin and luteinizing hormone levels in rats neonatally administered melatonin.

To obtain information on the chronobiological consequences of neonatal melatonin administration to rats, we examined the 24h variations of serum prolactin and luteinizing hormone (LH) levels in 21-, 25-, and 60-day-old male rats injected with 100 microg of melatonin or vehicle on the fifth day of life and kept under light from 08:00 to 20:00 daily. In 21-day-old rats, circulating prolactin varied diurnally in melatonin-treated rats only, showing a maximum at 16:00 and a secondary peak at 08:00. In 25-day-old rats, both vehicle- and melatonin-injected rats exhibited significant time-of-day-related changes in serum prolactin, with 77% of the variation in melatonin-injected rats explained by a single 24h component. Acrophase for prolactin rhythm of melatonin-treated rats occurred at 19:51. At 60 days of age, rats receiving vehicle or melatonin showed similar, significant 24h variations in serum prolactin, with acrophases at 17:31-18:15. Serum LH levels attained a maximum at midnight in 21-day-old rats treated with vehicle and at noon in those injected with melatonin. After a cosinor analysis, 71% of the variation in melatonin-injected rats was explained by a single 24h component, with the acrophase at 11:08. In 25-day-old rats, a complex pattern of serum LH concentration was found, with two maxima in vehicle-injected controls, at noon and midnight, and a maximum at noon together with a plateau from 20:00 to 04:00 in melatonin-treated rats. In 60-day-old rats, the maximum of serum LH was found at noon, with a similar extent showing in vehicle- and melatonin-treated animals. The acrophases were at 10:20 (vehicle) and 10:57 (melatonin) and did not differ significantly from that found in 21-day-old melatonin-treated rats. The results suggest that exposure to melatonin early in life may accelerate maturation of 24h prolactin and LH profiles toward an adult form.

Animals↗

PubMed1997

Aging attenuates diurnal variation in hamster locomotion, anxiolysis and GABA turnover.

A decrease in amplitude of wheel running circadian rhythms was found in old (18 month old) Syrian hamsters, as compared with young (3 month old.) animals. In a plus-maze paradigm, amplitude of variation of anxiety-related variables (2400 vs. 1600 h) was significantly impaired in aged hamsters. Cerebral cortex, hypothalamic and pineal gamma-aminobutyric acid (GABA) turnover was higher at night, amplitude of variation being significantly smaller in aged hamsters. The results further support the existence of impaired amplitude of circadian rhythms in aged Syrian hamsters.

Age Factors↗

PubMed1997

Picrotoxin-sensitive receptors mediate gamma-aminobutyric acid-induced modulation of synaptic plasticity in rat superior cervical ganglion.

Activity-dependent changes of synaptic efficacy in the superior cervical ganglion (SCG) can be prevented by gamma-aminobutyric acid (GABA). We have studied the effects of picrotoxin (PTX) on GABA-mediated inhibition of long-term potentiation (LTP) of synaptic transmission in the rat SCG. Compound action potentials were recorded extracellularly in the postganglionic internal carotid nerve in response to preganglionic nerve stimulation. PTX (100 microM) antagonized the inhibition by exogenous GABA (250 microM) of LTP induced by strong tetanic stimulation (20 Hz, 20s, supramaximal stimulation, partial blockade of transmission by hexamethonium). Additionally, PTX alone (50 microM) facilitated the induction of LTP by a weak tetanus (20 Hz, 5 s, submaximal stimulation). These results further support previous data indicating that activation of GABAA-like receptors can prevent the occurrence of synaptic plasticity at this peripheral synapse.

Animals↗

PubMed1997

Effect of local autonomic denervation on in vitro responsiveness of lymphocytes from rat submaxillary lymph nodes.

The local autonomic denervation of rat submaxillary lymph nodes was achieved by a unilateral sympathetic superior cervical ganglionectomy and/or the unilateral section of chorda tympani (that resulted in ipsilateral parasympathetic decentralization of the submandibular territory). This study was performed to determine: (1) whether local sympathetic and/or parasympathetic denervation of rat submaxillary lymph nodes brought about changes in lymph node cellularity, natural killer activity and lipopolysaaccharide (LPS)- and concanavalin A (Con A)-induced cell proliferation in Freund's adjuvant-injected rats; (2) whether the effect of the immunosuppressive drug cyclosporine in rat submaxillary lymph nodes was affected by a single or combined unilateral ganglionectomy plus decentralization. A unilateral ganglionectomy, or the combination of ganglionectomy plus decentralization, performed 7 days earlier, decreased significantly cellularity in ipsilateral submaxillary lymph nodes, while a unilateral decentralization failed to affect it. Natural killer activity increased ipsilaterally after ganglionectomy or decentralization, and decreased after the combined surgical procedure. LPS-induced cell proliferation augmented significantly after ganglionectomy or decentralization, while Con A-induced T lymphocyte proliferation remained unaffected. In the sham-operated side, cyclosporine decreased submaxillary lymph node cell number and natural killer activity, while it increased the proliferative response to LPS. The depressive effect of cyclosporine on lymph node cellularity was no longer observed in ganglionectomized or decentralized lymph nodes, but was found after the combined surgical denervation. Decentralization, or decentralization plus ganglionectomy, blunted the depressive effect of cyclosporine on natural killer activity. The stimulatory effect of cyclosporine on lymphocyte proliferation induced by LPS was reversed both by ganglionectomy or by decentralization and was suppressed by the combined surgical procedure. Neither treatment affected Con A-induced proliferation of T lymphocytes. The results further indicate that an appropriate sympathetic and parasympathetic local environment may be needed for immunomodulation, as well as for cyclosporine activity in lymphoid tissue.

Animals↗

PubMed1997

Diurnal changes in cyclosporine effect on ornithine decarboxylase and noradrenergic and cholinergic activities in submaxillary lymph nodes.

Diurnal changes in cyclosporine efficacy to affect ornithine decarboxylase activity, [3H]norepinephrine uptake and [3H]choline conversion into [3H]acetylcholine were examined in rat submaxillary lymph nodes. Cyclosporine (5 or 20 mg/kg) caused a dose-dependent decrease in lymph node ornithine decarboxylase, being active at 5 or 20 mg/kg in Freund's adjuvant-treated rats, and at 20 mg/kg in rats treated with the adjuvant's vehicle. In immunized rats the lower cyclosporine dose was ineffective when injected during the night. Cyclosporine increased lymph node [3H]norepinephrine uptake dose dependently, with significant differences between the 20 mg/kg dose and controls in vehicle-treated rats and between 5 or 20 mg/kg and controls in Freund's adjuvant-treated rats. In immunized rats, 5 mg/kg cyclosporine increased [3H]norepinephrine uptake when injected at 13:00 or 17:00 h. Both doses of cyclosporine augmented lymph node synthesis of [3H]acetylcholine to a similar extent. In immunized and non-immunized rats cyclosporine suppressed the diurnal rhythm of lymph node adrenergic and cholinergic activity found in controls. After unilateral sympathetic denervation (by superior cervical ganglionectomy) and/or unilateral parasympathetic decentralization (by chorda tympani section), cyclosporine (5 mg/kg) decreased Freund's adjuvant-induced activation of lymph node ornithine decarboxylase when injected at 17:00 or 01:00 h. On the sham-operated side, cyclosporine was effective when injected at 17:00 h only. Decentralization, or a combined ganglionectomy plus decentralization, decreased lymph node ornithine decarboxylase activity. The results active regulation of the effects of cyclosporine in submaxillary lymph nodes by local autonomic nerves.

Animals↗

PubMed1997

Effect of melatonin on serum cholesterol and phospholipid levels, and on prolactin, thyroid-stimulating hormone and thyroid hormone levels, in hyperprolactinemic rats.

The effects of melatonin treatment and pituitary transplants on serum total and free cholesterol levels, cholesterol esterification index, phospholipid levels and prolactin, thyroid-stimulating hormone (TSH), thyroxine (T4) and triiodothyronine (T3) levels were examined in rats. Male rats were grafted an anterior pituitary under the kidney capsule or were sham-operated on day 30th of life. Thirty days later, the rats received 4 daily s.c. injections of melatonin (25, 50 or 100 microg/rat) or vehicle, 2 h before lights off, and were killed 15 h after the last injection, and after a 24-hour fasting period. In pituitary-grafted rats, a decrease in serum free cholesterol with unmodified total cholesterol levels, and thus an augmented cholesterol esterification index, occurred. Pituitary-grafted rats showed also an increase in serum phospholipids. In control, but not in pituitary-grafted rats, melatonin injection decreased free cholesterol without modifying total cholesterol levels. Melatonin treatment (50 microg/day or greater) normalized the augmented serum phospholipid levels found in pituitary-grafted rats and increased serum phospholipids in control rats. Melatonin injection also reduced the high serum prolactin and T3 levels found in pituitary-grafted rats, and decreased T4 concentration in control rats. Neither melatonin nor pituitary grafts modified serum TSH concentration. The results demonstrate that melatonin counteracts in part lipid disturbances of hyperprolactinemic rats and lowers free plasma cholesterol and augmented serum phospholipids in control rats.

Animals↗

PubMed1997

The influence of cervical sympathetic neurons on parathyroid hormone and calcitonin release in the rat: independence of pineal mediation.

The objective of this study was to evaluate the involvement of the pineal gland in modulation of parathyroid hormone (PTH) and calcitonin release found in rats after changes in activity of cervical sympathetic nerves. The response of serum PTH to a hypocalcemia produced by EDTA injection, and of serum calcitonin to a hypercalcemia produced by administering calcium chloride, were studied in rats at the time of the wallerian degeneration of regional sympathetic nerves (i.e., 16 hr after superior cervical ganglionectomy, SCGx). Rats received a pinealectomy or its sham-operation 4 days before SCGx. During wallerian degeneration of nerves after SCGx, a higher hypocalcemia and a lower PTH response were found as compared to sham-SCGx rats, regardless of whether the pineal gland was present or not. When the response of calcitonin to a bolus injection of calcium chloride was assessed, rats subjected to SCGx 16 hr earlier showed a depressed calcitonin release, which was also unaffected after pinealectomy. To a similar extent in pinealectomized and sham-pinealectomized rats, a mild stress given by the subcutaneous injection of turpentine oil brought about a greater hypocalcemia after EDTA, concomitantly with a higher PTH secretory response. In turpentine oil-injected rats, the rise of serum calcitonin was significantly greater than that of vehicle-treated rats, regardless of pineal presence. The results further indicate that cervical autonomic nerves constitute a pathway through which the brain modulates calcium homeostasis and do not support the participation of the pineal gland in short term changes of PTH or calcitonin release.

Animals↗

PubMed1997

Twenty-four hour rhythms of serum prolactin, growth hormone and luteinizing hormone levels, and of medial basal hypothalamic corticotropin-releasing hormone levels and dopamine and serotonin metabolism in rats neonatally administered melatonin.

To obtain information on long-term circadian consequences of administering melatonin neonatally to rats, we assessed the 24-hour rhythms of 1) serum prolactin (PRL), luteinizing hormone (LH), and growth hormone (GH), and 2) medial basal hypothalamic dopamine (DA) and serotonin (5-HT) metabolism and corticotropin-releasing hormone (CRH) content in 60-day old male rats injected with 100 micrograms of melatonin on the 5th day of life. Controls receiving vehicle alone showed serum PRL concentration (when 60 days of age) attaining its maximum at the end of the light period (i.e., at 2000 hr), while in melatonin-injected rats high PRL values were found between 1200 and 2000 hr. Twenty-four hour changes in serum LH levels exhibited a maximum at noon, and to a similar extent in vehicle- and melatonin-treated rats. Neonatal melatonin injection did not affect serum GH concentration when the rats were adult. In the medial basal hypothalamus (MBH), the dihydroxyphenyl acetic acid (DOPAC)/ DA ratio attained a maximum at midnight, its amplitude being significantly higher in melatonin- than in vehicle-treated rats. Neonatally melatonin-injected rats also exhibited a second maximum in DOPAC/DA ratio at noon, coinciding with a minimum in DA levels of MBH. The 5-hydroxyindoleacetic acid (5-HIAA)/5-HT ratio in MBH showed significant diurnal variations in vehicle-injected controls with maxima at 1200 and 0400 hr, while in melatonin-treated rats a single maximum occurred at 2400 hr. These maximum correlated with minima in 5-HT content of MBH. Neonatal melatonin injection brought about a significant increase in the CRH content of MBH, as well as distortion of its diurnal rhythmicity, a maximum being found at noon in controls and at 1800 hr in melatonin-treated rats. The results indicate that exposure to melatonin early in life affects subsequent diurnal rhythmicity of PRL release, and of DA and 5-HT turnover and CRH content in the MBH of rats.

Analysis of Variance↗

PubMed1997

Effect of pinealectomy, superior cervical ganglionectomy, or melatonin treatment on 24-hour rhythms in ornithine decarboxylase and tyrosine hydroxylase activities of rat spleen.

Diurnal variations in splenic ornithine decarboxylase and tyrosine hydroxylase activities were examined in rats subjected to pinealectomy, bilateral superior cervical ganglionectomy, or their respective sham operations. Rats were treated with Freund's complete adjuvant or its vehicle 2 days before sacrifice. After immunization, splenic ornithine decarboxylase activity was augmented 5-6-fold. In both immunized and nonimmunized sham-operated rats, significant diurnal variations in ornithine decarboxylase activity were detectable, with a maximum at early morning, acrophases after Cosinor analysis varying from 0845 to 1048h. In pinealectomized or superior cervical ganglionectomized, immunized rats, ornithine decarboxylase activity attained values 22-27% lower than those of immunized sham-operated controls, while amplitude decreased significantly by 27-30%. Administration of melatonin (30 microg/animal s.c. at late evening for 11 days in immunized rats) significantly augmented mesor levels of splenic ornithine decarboxylase activity and increased the amplitude of the diurnal rhythm both in pinealectomized and in superior cervical ganglionectomized rats. Melatonin treatment also augmented rhythm mesor in immunized, sham-ganglionectomized rats, as well as rhythm amplitude in immunized and nonimmunized, sham-ganglionectomized rats. Splenic tyrosine hydroxylase activity attained its maximum at late afternoon and early night, with acrophases varying from 1800 to 2023h. Immunization significantly increased mesor values of splenic tyrosine hydroxylase activity, whereas neither pinealectomy nor superior cervical ganglionectomy affected circadian rhythm parameters. Melatonin treatment augmented mesor values of tyrosine hydroxylase rhythm and increased its amplitude in pinealectomized, ganglionectomized, or sham-operated rats. The results are compatible with the view that the pineal gland plays a role in circadian changes of immune responsiveness in rat spleen via an immunopotentiating effect of melatonin on splenic cell proliferation.

Animals↗

PubMed1997

Melatonin site and mechanism of action: single or multiple?

By affecting the entrainment pathways of the biologic clock, melatonin has a major influence on the circadian and seasonal organization of vertebrates. In addition, a number of versatile functions that far transcend melatonin actions on photoperiodic time measurement and circadian entrainment have emerged. Melatonin is a free radical scavenger and antioxidant and it has a significant immunomodulatory activity, being presumably a major factor in an organism's defense toxic agents and invading organisms. Besides affecting specific receptors in cell membranes to exert its effects, the interaction of melatonin with nuclear receptor sites and with intracellular proteins, like calmodulin or tubulin-associated proteins, as well as the direct antioxidant effects of melatonin, may explain many general functions of the pineal hormone.

Animals↗