PubMed Health⌕ Search

Biomedical subjects

D P Cardinali

Publications and source records attributed to D P Cardinali.

At least 19 recordsLinked to original sources

Melatonin in the eye: implications for glaucoma.

Melatonin synthesis occurs in the retina of most animals as well as in humans. Circadian oscillators that control retinal melatonin synthesis have been identified in the eyes of different animal species. The presence of melatonin receptors is demonstrable by immunocytochemical studies of ocular tissues. These receptors may have different functional roles in different parts of the eye. In view that melatonin is a potent antioxidant molecule, it can be effective in scavenging free radicals that are generated in ocular tissues. By this mechanism melatonin could protect the ocular tissues against disorders like glaucoma, age-related macular degeneration, retinopathy of prematurity, photo-keratitis and cataracts. Although an increased intraocular pressure is an important risk factor in glaucoma, other concomitant phenomena like increased glutamate levels, altered nitric oxide metabolism and increased free radical generation seem to play a significant role in its pathogenesis. Data are discussed indicating that melatonin, being an efficient antioxidant with antinitridergic properties, has a promising role in the treatment and management of glaucoma.

Animals↗

Melatonin in Alzheimer's disease and other neurodegenerative disorders.

Increased oxidative stress and mitochondrial dysfunction have been identified as common pathophysiological phenomena associated with neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). As the age-related decline in the production of melatonin may contribute to increased levels of oxidative stress in the elderly, the role of this neuroprotective agent is attracting increasing attention. Melatonin has multiple actions as a regulator of antioxidant and prooxidant enzymes, radical scavenger and antagonist of mitochondrial radical formation. The ability of melatonin and its kynuramine metabolites to interact directly with the electron transport chain by increasing the electron flow and reducing electron leakage are unique features by which melatonin is able to increase the survival of neurons under enhanced oxidative stress. Moreover, antifibrillogenic actions have been demonstrated in vitro, also in the presence of profibrillogenic apoE4 or apoE3, and in vivo, in a transgenic mouse model. Amyloid-beta toxicity is antagonized by melatonin and one of its kynuramine metabolites. Cytoskeletal disorganization and protein hyperphosphorylation, as induced in several cell-line models, have been attenuated by melatonin, effects comprising stress kinase downregulation and extending to neurotrophin expression. Various experimental models of AD, PD and HD indicate the usefulness of melatonin in antagonizing disease progression and/or mitigating some of the symptoms. Melatonin secretion has been found to be altered in AD and PD. Attempts to compensate for age- and disease-dependent melatonin deficiency have shown that administration of this compound can improve sleep efficiency in AD and PD and, to some extent, cognitive function in AD patients. Exogenous melatonin has also been reported to alleviate behavioral symptoms such as sundowning. Taken together, these findings suggest that melatonin, its analogues and kynuric metabolites may have potential value in prevention and treatment of AD and other neurodegenerative disorders.

Journal Article↗

Effect of melatonin treatment on oxygen consumption by rat liver mitochondria.

The objective of this study was to examine the in vivo effect of melatonin on rat mitochondrial liver respiration. Two experiments were performed: For experiment 1, adult male rats received melatonin in the drinking water (16 or 50 microg/ml) or vehicle during 45 days. For experiment 2, rats received melatonin in the drinking water (50 microg/ml) for 45 days, or the same amount for 30 days followed by a 15 day-withdrawal period. At sacrifice, a liver mitochondrial fraction was prepared and oxygen consumption was measured polarographically in the presence of excess concentration of DL-3-beta-hydroxybutyrate or L-succinate. Melatonin treatment decreased Krebs' cycle substrate-induced respiration significantly at both examined doses. The stimulation of mitochondrial respiration caused by excess concentration of substrate recovered after melatonin withdrawal. Basal state 4 respiration was not modified by melatonin. Melatonin, by curtailing overstimulation of cellular respiration caused by excess Krebs' cycle substrates, can protect the mitochondria from oxidative damage.

3-Hydroxybutyric Acid↗

Circadian rhythms of prolactin secretion in neonatal female rabbits after acute separation from their mothers.

Newborn rabbits (Oryctolagus cuniculus) are only nursed for 3-5 min every 24 h and show a circadian increase in activity in anticipation of nursing. The objective of this study was to determine, in neonatal female rabbits after acute separation from the doe for 48 h, the changes in 24-h rhythms of plasma prolactin and median eminence and anterior pituitary concentration of dopamine (DA) and serotonin (5HT). In addition, median eminence concentration of the excitatory amino acid transmitters glutamate (GLU) and aspartate (ASP) and of the inhibitory amino acid transmitters gamma-aminobutyric acid (GABA) and taurine (TAU) was measured. A significant 21% increase of circulating prolactin occurred in isolated pups. In controls pups, plasma prolactin levels showed two peaks, during the first half of the light phase and at the beginning of the scotophase, respectively. In the isolated pups, a phase advance of about 4 h occurred for the two prolactin peaks. Hemicircadian changes of median eminence DA were found in controls, whereas a single daily peak (at 17:00 h) was found in the separated pups. Plasma prolactin and median eminence DA correlated significantly and inversely in the control group only. Pituitary DA content exhibited a single peak in controls and a hemicircadian pattern in isolated pups. Plasma prolactin and pituitary DA correlated significantly in isolated pups only 00000. Pup isolation decreased median eminence 5HT levels, augmented pituitary 5HT levels and disrupted their 24 h rhythmicity. Circulating prolactin correlated inversely with median eminence 5HT and directly with adenohypophysial 5HT only in controls. Isolation of pups generally modified the 24 h pattern of median eminence excitatory and inhibitory amino acid content by causing a prominent decrease at the beginning of the light phase. The results indicate that circadian rhythmicity of prolactin secretory mechanisms in female rabbit pups is significantly affected by pup's isolation from the doe.

Animals↗

Twenty-four hour rhythm of plasma prolactin in female rabbit pups. Correlation with hypothalamic and adenohypophysial dopamine, serotonin, gamma-aminobutyric acid and taurine content.

Lactation in the rabbit is a nocturnal activity, extremely short and regular, that can be a strong synchronizer for the development of circadian rhythmicity in the pups. In the present study, 24-h rhythmicity of plasma prolactin and median eminence and anterior pituitary content of dopamine (DA), serotonin (5HT), gamma-aminobutyric acid (GABA) and taurine were examined in 11 days old female pups kept under 16 h light:8 h dark photoperiods (lights on at 08:00 h). Groups of six to seven female rabbit pups were killed by decapitation at six different time points throughout a 24-h cycle, starting at 09:00 h. Plasma prolactin levels changed significantly throughout the day, showing two peaks, one at first half of rest span (at 13:00 h) and another one at the beginning of the scotophase (at 01:00 h), just preceding doe visit. Median eminence DA content changed in a bimodal way as a function of time of day, displaying two maxima, at the beginning of the rest span and of the activity phase. Median eminence DA and plasma prolactin correlated significantly in an inverse way. Two maxima in median eminence 5HT levels were found, about 4 h in advance to the prolactin peaks. Circulating prolactin correlated inversely with median eminence 5HT content and directly with adenohypophysial 5HT content. Median eminence GABA content reached its maximum at the beginning of the scotophase and correlated significantly with plasma prolactin concentration. A positive correlation between plasma prolactin and adenohypophysial taurine content was observed. These results show that the circadian rhythmicity in prolactin secretory mechanisms in female rabbit pups develops during the early neonatal life.

Aging↗

Melatonin: Nature's most versatile biological signal?

Melatonin is a ubiquitous molecule and widely distributed in nature, with functional activity occurring in unicellular organisms, plants, fungi and animals. In most vertebrates, including humans, melatonin is synthesized primarily in the pineal gland and is regulated by the environmental light/dark cycle via the suprachiasmatic nucleus. Pinealocytes function as 'neuroendocrine transducers' to secrete melatonin during the dark phase of the light/dark cycle and, consequently, melatonin is often called the 'hormone of darkness'. Melatonin is principally secreted at night and is centrally involved in sleep regulation, as well as in a number of other cyclical bodily activities. Melatonin is exclusively involved in signaling the 'time of day' and 'time of year' (hence considered to help both clock and calendar functions) to all tissues and is thus considered to be the body's chronological pacemaker or 'Zeitgeber'. Synthesis of melatonin also occurs in other areas of the body, including the retina, the gastrointestinal tract, skin, bone marrow and in lymphocytes, from which it may influence other physiological functions through paracrine signaling. Melatonin has also been extracted from the seeds and leaves of a number of plants and its concentration in some of this material is several orders of magnitude higher than its night-time plasma value in humans. Melatonin participates in diverse physiological functions. In addition to its timekeeping functions, melatonin is an effective antioxidant which scavenges free radicals and up-regulates several antioxidant enzymes. It also has a strong antiapoptotic signaling function, an effect which it exerts even during ischemia. Melatonin's cytoprotective properties have practical implications in the treatment of neurodegenerative diseases. Melatonin also has immune-enhancing and oncostatic properties. Its 'chronobiotic' properties have been shown to have value in treating various circadian rhythm sleep disorders, such as jet lag or shift-work sleep disorder. Melatonin acting as an 'internal sleep facilitator' promotes sleep, and melatonin's sleep-facilitating properties have been found to be useful for treating insomnia symptoms in elderly and depressive patients. A recently introduced melatonin analog, agomelatine, is also efficient for the treatment of major depressive disorder and bipolar affective disorder. Melatonin's role as a 'photoperiodic molecule' in seasonal reproduction has been established in photoperiodic species, although its regulatory influence in humans remains under investigation. Taken together, this evidence implicates melatonin in a broad range of effects with a significant regulatory influence over many of the body's physiological functions.

Animals↗

Could agomelatine be the ideal antidepressant?

Depressive disorders are a common cause of chronic and recurrent psychiatric dysfunction, constituting the fourth leading cause of global diseases. Depression is associated with a high rate of morbidity and mortality, and is a leading cause of global disability. Despite the effectiveness of most currently available antidepressants, many of them have a number of undesirable side effects. Agomelatine is the first melatonin (MT)(1)/MT(2) agonist having 5-hydroxytryptamine (5-HT)(2C) and 5-HT(2B) antagonist properties and antidepressant activity. Agomelatine is effective in several animal models of depression and anxiety. In addition, three large, multicenter, multinational, placebo-controlled studies and several double-blind, placebo-controlled trials of agomelatine have demonstrated that it is a clinically effective and well-tolerated antidepressant in acute trials. Since currently available antidepressants are not always adequate to cause complete remission of symptoms in severely depressed patients, the superior rate of response achieved with agomelatine in this group of patients underlines its future for clinical use in depressive disorders. In summary, the clinical advantage of agomelatine is attributed to its novel mechanism of action, which helps not only to exert antidepressant action, but also to regulate the sleep-wake rhythm.

Acetamides↗

Melatonin, immune function and aging.

Aging is associated with a decline in immune function (immunosenescence), a situation known to correlate with increased incidence of cancer, infectious and degenerative diseases. Innate, cellular and humoral immunity all exhibit increased deterioration with age. A decrease in functional competence of individual natural killer (NK) cells is found with advancing age. Macrophages and granulocytes show functional decline in aging as evidenced by their diminished phagocytic activity and impairment of superoxide generation. There is also marked shift in cytokine profile as age advances, e.g., CD3+ and CD4+ cells decline in number whereas CD8+ cells increase in elderly individuals. A decline in organ specific antibodies occurs causing reduced humoral responsiveness. Circulating melatonin decreases with age and in recent years much interest has been focused on its immunomodulatory effect. Melatonin stimulates the production of progenitor cells for granulocytes-macrophages. It also stimulates the production of NK cells and CD4+ cells and inhibits CD8+ cells. The production and release of various cytokines from NK cells and T-helper lymphocytes also are enhanced by melatonin. Melatonin presumably regulates immune function by acting on the immune-opioid network, by affecting G protein-cAMP signal pathway and by regulating intracellular glutathione levels. Melatonin has the potential therapeutic value to enhance immune function in aged individuals and in patients in an immunocompromised state.

Journal Article↗

Melatonin and sleep in aging population.

The neurohormone melatonin is released from the pineal gland in close association with the light-dark cycle. There is a temporal relationship between the nocturnal rise in melatonin secretion and the 'opening of the sleep gate' at night. This association, as well as the sleep promoting effect of exogenous melatonin, implicates the pineal product in the physiological regulation of sleep. Aging is associated with a significant reduction in sleep continuity and quality. A decreased production of melatonin with age is documented in a majority of studies. Diminished nocturnal melatonin secretion with severe disturbances in sleep/wake rhythm has been consistently reported in Alzheimer's disease (AD). A recent survey on the effects of melatonin in sleep disturbances, including all age groups, failed to document significant and clinically meaningful effects of exogenous melatonin on sleep quality, efficiency and latency. However, in clinical trials involving elderly insomniacs and AD patients suffering from sleep disturbances exogenous melatonin has repeatedly been found to be effective in improving sleep. The results indicate that exogenous melatonin is more effective to promote sleep in the presence of a diminished production of endogenous melatonin. A MT1/MT2 receptor analog of melatonin (ramelteon) has recently been introduced as a new type of hypnotics with no evidence of abuse or dependence.

Aged↗

Role of melatonin in neurodegenerative diseases.

The pineal product melatonin has remarkable antioxidant properties. It scavenges hydroxyl, carbonate and various organic radicals, peroxynitrite and other reactive nitrogen species. Melatonyl radicals formed by scavenging combine with and, thereby, detoxify superoxide anions in processes terminating the radical reaction chains. Melatonin also enhances the antioxidant potential of the cell by stimulating the synthesis of antioxidant enzymes like superoxide dismutase, glutathione peroxidase and glutathione reductase, and by augmenting glutathione levels. The decline in melatonin production in aged individuals has been suggested as one of the primary contributing factors for the development of age-associated neurodegenerative diseases, e.g., Alzheimer's disease. Melatonin has been shown to be effective in arresting neurodegenerative phenomena seen in experimental models of Alzheimer's disease, Parkinsonism and ischemic stroke. Melatonin preserves mitochondrial homeostasis, reduces free radical generation, e.g., by enhancing mitochondrial glutathione levels, and safeguards proton potential and ATP synthesis by stimulating complex I and IV activities. Therapeutic trials with melatonin have been effective in slowing the progression of Alzheimer's disease but not of Parkinson's disease. Melatonin's efficacy in combating free radical damage in the brain suggests that it may be a valuable therapeutic agent in the treatment of cerebral edema after traumatic brain injury.

Aging↗

Experimental allergic encephalomyelitis in male Lewis rats subjected to calorie restriction.

This work analyzes the effect of calorie restriction on the development of experimental allergic encephalomyelitis (EAE) in Lewis rats. Plasma levels of ACTH, corticosterone, prolactin and growth hormone (GH) and mitogenic responses in submaxillary lymph nodes were measured. Male Lewis rats (6 weeks-old) were submitted to a calorie restriction equivalent to 66% of food restriction or to a normal diet. Fifteen days later, rats were injected with complete Freund's adjuvant plus spinal chord homogenate (SCH) or with complete Freund's adjuvant alone. Rats were monitored daily for clinical signs of EAE and were killed on day 15 after immunization. Only rats subjected to normal diet exhibited clinical signs of the disease. The increase in plasma ACTH and corticosterone found after SCH immunization in controls was not detectable in calorie restricted rats. Likewise, the correlation between circulating ACTH and corticosterone was no longer found after calorie restriction. Generally, calorie restriction by itself augmented plasma ACTH or corticosterone and this increase was not further amplified by SCH immunization. Only calorie restricted rats exhibited augmented plasma prolactin levels after SCH immunization, and decreased plasma GH levels regardless of immunization. Calorie restriction depressed the mitogenic response of lymphoid cells to concanavalin A but not to lipopolysaccharide. Calorie restricted rats did not exhibit augmented mitogenic response to concanavalin A following SCH immunization as those found in controls. The results are compatible with the view that the course of EAE can be significantly modified by caloric restriction.

Adrenocorticotropic Hormone↗

Changes of prolactin regulatory mechanisms in aging: 24-h rhythms of serum prolactin and median eminence and adenohypophysial concentration of dopamine, serotonin, (gamma-aminobutyric acid, taurine and somatostatin in young and aged rats.

Twenty-four hour rhythmicity of serum prolactin and median eminence and anterior pituitary content of dopamine (DA), serotonin (5HT), gamma-aminobutyric acid (GABA), taurine and somatostatin were examined in 2 months-old and 18-20 months-old Wistar male rats. The concentration of prolactin was higher in aged rats, with peaks in both groups of rats at the early phase of the activity span. Median eminence DA content of young rats attained its maximum at the middle of rest span and decreased as prolactin levels augmented while the lowest values of adenohypophysial DA were observed at the time of prolactin peak. DA rhythmicity disappeared in aged rats. GABA content of median eminence and adenohypophysis was lower in aged rats, with maximal values of median eminence GABA at light-dark transition in young rats and at the second half of activity span in aged rats. Serum prolactin correlated positively with median eminence GABA in young rats and negatively with pituitary GABA in young and aged rats. Median eminence somatostatin peaked at the beginning of the activity phase (young rats) or at the end of the rest phase (aged rats). Prolactin levels and somatostatin content correlated significantly in young rats only. Median eminence and pituitary 5HT and taurine content did not change with age. The results indicate disruption of prolactin regulatory mechanisms with aging in rats.

Aging↗

Day-night changes in plasma melatonin levels, synaptophysin expression and ultrastructural properties of pinealocytes in developing female sheep under natural long and short photoperiods.

The aim of the present study was to analyze the 24-h rhythm in plasma melatonin concentration and the day-night differences in synaptophysin expresion and ultrastructural characteristics of the pinealocytes in developing female sheep. Ewes of three different ages were examined: infantile (1-6 months old), pubertal and early fertile age (9-24 months old) and adult (36-60 months old). Experiments were conducted under natural non-stimulatory (long) and stimulatory (short) photoperiods. The obtained results were similar for both analyzed photoperiods. Plasma melatonin concentration, measured in samples obtained every 4 h, showed a similar pattern in the three age groups, with peak values at 02:00 h and troughs at 14:00 h. Mean value of plasma melatonin levels in 9-24 month-old sheep was significantly greater than that in younger or older sheep. The weight of pineal glands obtained at night (02:00 h) was significantly higher than in daylight (14:00 h). Pubertal and early fertile sheep had the largest pineal glands. The pineal volume, and the total number of pinealocytes per gland of 9-24 months-old sheep differed significantly from that of younger or older sheep. The pineal volume, and the mean volume of pinealocytes was significantly greater in animals killed at night. Number of pinealocytes did not vary between animals killed during daylight or at night. The mean volumen of pinealocytes did not show statistical differences between the age groups. In quantitative ultrastructural analysis of pinealocyte cells, the relative volume of mitochondria, rough endoplasmic reticulum and Golgi complexes was significantly greater in 9-24 month-old sheep and in animals killed at night. The relative volume of lipid droplets was highest in older sheep. Collectively, the data support the existence of developmental changes in pinealocyte morphology and quantity, partially in coincidence with a higher melatonin secretion rate.

Animals↗

Circadian rhythms in airline pilots submitted to long-haul transmeridian flights.

BACKGROUND: Circadian rhythms shift out of phase after transmeridian flights. Desynchronization between body rhythms and the environment is linked to jet lag, which depends on age, flight direction, and number of time zones crossed. METHODS: To investigate this problem in airline pilots, we performed a multivariate analysis of their circadian systems during Madrid-Mexico-Madrid flights (-7 time zones, n = 12) and Madrid-Tokyo-Madrid flights (+8 time zones, n = 21). Telemetry was used to record pilots' activity, skin temperature, and heart rate, obtaining 6 d of continuous data, including 2 d before the flight, the flights themselves, 2 d at the stopover, and 1 d after the return flight. Time series were analyzed by cosinor, and the resulting parameters of the rhythms were compared by ANOVA and Tukey contrasts in every category formed by the age groups (under and over 50 yr old) and flight direction groups. Subjective time estimation of short, intermediate, and long intervals was recorded. Other psychological variables were measured, including anxiety, tiredness, and performance. RESULTS AND CONCLUSIONS: Activity/rest and heart rate rhythms appeared to be linked to a "weak oscillator." Temperature rhythms manifested a rigid response after the phase shifts of the light/dark cycle, closely related to the biological clock. Subjective time appreciation tended to be overestimated without exhibiting a clear circadian component, but attributable to fatigue and stress. Psychometric evaluation showed that desynchronization affected all the pilots. Some results showed an age-related variability with a more marked influence in younger pilots. No consistent effects regarding flight direction were found.

Activity Cycles↗

Effect of melatonin on bone metabolism in ovariectomized rats.

To assess the effect of pharmacological dose of melatonin on bone metabolism in ovariectomized rats, urinary deoxypyridinoline (a marker of bone resorption) and calcium excretion, circulating levels of calcium, phosphorus and bone alkaline phosphatase activity (a marker of bone formation), and bone mineral density (BMD), mineral content (BMC) and bone area (BA) of total body, were measured in adult rats for up to 60 days after surgery. Rats received melatonin in the drinking water (25 microg/ml water) or drinking water alone. Urinary deoxypyridinoline increased significantly after ovariectomy by 51% (30 days after surgery) and by 47% (60 days after surgery). The increase in urinary deoxypyridinoline found 30 days after ovariectomy was not observed in melatonin-treated rats. Urinary calcium concentration was similar in the 4 experimental groups studied, as was the circulating calcium concentration at every time interval examined. Fifteen days after surgery, a significant increase in serum phosphorus and bone alkaline phosphatase levels occurred in ovariectomized rats receiving melatonin as compared to their controls. Sixty days after surgery BMD, BMC and BA decreased significantly in ovariectomized rats, an effect not modified by melatonin. Serum estradiol decreased significantly by 30 days after ovariectomy to attain values close to the limit of detection of the assay by 60 days after ovariectomy. The results support the conclusion that a pharmacological amount of melatonin modifies bone remodeling after ovariectomy and that the effect may need adequate concentrations of estradiol.

Absorptiometry, Photon↗

Age-dependent changes in 24-hour rhythms of catecholamine content and turnover in hypothalamus, corpus striatum and pituitary gland of rats injected with Freund's adjuvant.

BACKGROUND: Little information is available on the circadian sequela of an immune challenge in the brain of aged rats. To assess them, we studied 24-hour rhythms in hypothalamic and striatal norepinephrine (NE) content, hypothalamic and striatal dopamine (DA) turnover and hypophysial NE and DA content, in young (2 months) and aged (18-20 months) rats killed at 6 different time intervals, on day 18th after Freund's adjuvant or adjuvant's vehicle administration. RESULTS: Aging decreased anterior and medial hypothalamic NE content, medial and posterior hypothalamic DA turnover, and striatal NE concentration and DA turnover. Aging also decreased NE and DA content in pituitary neurointermediate lobe and augmented DA content in the anterior pituitary lobe. Immunization by Freund's adjuvant injection caused: (i) reduction of DA turnover in anterior hypothalamus and corpus striatum; (ii) acrophase delay of medial hypothalamic DA turnover in old rats, and of striatal NE content in young rats; (iii) abolition of 24-h rhythm in NE and DA content of neurointermediate pituitary lobe, and in DA content of anterior lobe, of old rats. CONCLUSIONS: The decline in catecholamine neurotransmission with aging could contribute to the decrease of gonadotropin and increase of prolactin release reported in similar groups of rats. Some circadian responses to immunization, e.g. suppression of 24-h rhythms of neurointermediate lobe NE and DA and of anterior lobe DA were seen only in aged rats.

Aging↗

Effect of unilateral superior cervical ganglionectomy on mandibular incisor eruption rate in rats.

To assess the effect of sympathectomy on rat tooth eruption, the effect of a unilateral superior cervical ganglionectomy (SCGx) on eruption rate of ipsi- and contralateral lower incisors was examined. Two experiments were performed. In a first experiment, the eruption rate of ipsilaterally denervated incisors was similar to that of contralaterally innervated incisors, when assessed for up to 28 days after surgery. In a second experiment, under conditions of unilateral unimpeded eruption of incisors performed ipsilaterally or contralaterally to a unilateral SCGx, a significantly lower eruption rate of denervated incisors at the impeded eruption side, and a significantly higher eruption rate of denervated incisors at the unimpeded side were observed, when computed every 2 days. Significant differences in individual Student's t tests at every time interval occurred mainly during the first and the last week of examination. When average daily eruption rate was computed in weekly intervals, a significant interaction between SCGx and the side of impeded or unimpeded eruption was found in a factorial ANOVA, that is, for each of the 4 weeks of examination, sympathetically denervated incisors showed lower eruption rates at the impeded eruption side, and higher eruption rates at the unimpeded side. These results indicate that incisor eruption is not modified by a local sympathetic denervation unless the contralateral lower rat incisor is cut out of occlusion.

Animals↗

Effect of parasympathetic decentralization on interferon-gamma release from rat submandibular lymph nodes in vitro.

The aim of this study was to examine the regulation of interferon (IFN)-gamma release by cells from submandibular lymph nodes of rats subjected to a unilateral parasympathetic decentralization by severing the ipsilateral chorda tympani 7 days earlier. Cells obtained from contralateral sham-operated submandibular lymph nodes were employed as control. Parasympathetic decentralization of lymph nodes resulted in significantly less IFN-gamma release as compared to that found in innervated lymph nodes. Mitogens (lipopolysaccharide, concanavalin A) stimulated IFN-gamma release in cells derived from the innervated lymph nodes only. The muscarinic agonist metacholine decreased IFN-gamma release in cells derived from innervated lymph nodes. At the highest concentration employed (10(-4) M), metacholine suppressed the stimulatory effect of mitogens on IFN-gamma release in cells of innervated lymph nodes while the muscarinic antagonist atropine (10(-8) - 10(-4) M) lacked to affect IFN-gamma release. Addition of nicotine (10(-5) - 10(-3) M) failed to modify IFN-gamma release. The results support the occurrence of significant effects of local parasympathetics in modulating IFN-gamma release by submandibular lymph nodes.

Animals↗