Peripheral Melatonin Research Articles

Species sensitivities to artificial light at night: A phylogenetically controlled multilevel meta-analysis on melatonin suppression.

The rapid urbanization of our world has led to a surge in artificial lighting at night (ALAN), with profound effects on wildlife. Previous research on wildlife's melatonin, a crucial mechanistic indicator and mediator, has yielded inconclusive evidence due to a lack of comparative analysis. We compiled and analysed an evidence base including 127 experiments with 437 observations across 31 wild vertebrates using phylogenetically controlled multilevel meta-analytic models. The evidence comes mainly from the effects of white light on melatonin suppression in birds and mammals. We show a 36% average decrease in melatonin secretion in response to ALAN across a diverse range of species. This effect was observed for central and peripheral melatonin, diurnal and nocturnal species, and captive and free-living populations. We also reveal intensity-, wavelength-, and timing-dependent patterns of ALAN effects. Exposure to ALAN led to a 23% rise in inter-individual variability in melatonin suppression, with important implications for natural selection in wild vertebrates, as some individuals may display higher tolerance to ALAN. The cross-species evidence has strong implications for conservation of wild populations that are subject to natural selection of ALAN. We recommend measures to mitigate harmful impacts of ALAN, such as using 'smart' lighting systems to tune the spectra to less harmful compositions.

Seasonal plasticity in immunocompetent cytokines (IL-2, IL-6, and TNF-α), myeloid progenitor cell (CFU-GM) proliferation, and LPS-induced oxido-inflammatory aberrations in a tropical rodent Funambulus pennanti: role of melatonin.

In seasonal breeders, photoperiods regulate the levels of circulatory melatonin, a well-known immunomodulator and an antioxidant. Melatonin is known to play a complex physiological role in maintaining the immune homeostasis by affecting cytokine production in immunocompetent cells. In this study, we have quantified seasonal and temporal variations in immunocompetent cytokines-IL-2, IL-6, and TNF-α-and circulatory corticosterone along with in- vitro proliferation of bone marrow-derived granulocyte macrophage-colony forming unit (CFU-GM) progenitor cells of a tropical seasonal breeder Funambulus pennanti (northern palm squirrel). Transient variations in antioxidant status of seasonal breeders might be due to the fluctuations associated with immunity and inflammation. Further,to establish a direct immunomodulatory effect of photoperiod, we recorded the LPS-induced oxidative and inflammatory responses of squirrels by housing them in artificial photoperiodic chambers mimicking summer and winter seasons respectively. We observeda marked variation in cytokines level, melatonin, and corticosterone , and CFU-GM cell proliferation during summer and winter seasons. High Peripheral melatonin levels directly correlated with cytokineIL-2 levels, and inversely correlated with TNF-α, and circulatory corticosterone level. LPS-challenged squirrels housed in short photoperiod (10L:14D; equivalent to winter days) showed a marked reduction in the components of the inflammatory cascade, CRP, TNF-α, IL-6, NOx, NF-κB, Cox-2, and PGES, with an overall improvement in antioxidant status when compared to squirrels maintained under a long photoperiod (16L:8D; equivalent to summer days). Our results underline the impact of seasonality, photoperiod, and melatonin in maintaining an intrinsic redox-immune homeostasis which helps the animal to withstand environmental stresses.

Uykusuzluğu tedavi etmek için kullanılan Ramelteon, osteoporoz oluşumunu azaltabilir

Aim: Melatonin promoted osteoblast differentiation and causes an increase in levels of markers of bone differentiation and proliferation. Ramelteon (RAMEL) activates melatonin receptors and binds to these receptors as non-selective. In this study, we investigated the preventive effects of the melatonin agonist RAMEL on osteoporosis by radiological, histological, and molecularly.Methods: Groups 1: Control, Group 2: Osteoporosis: Overectomized group (OP), Group 3: OP + ramelteon 2 mg/kg, Group 4: OP + ramelteon 4 mg/kg. 24 animals underwent bilateral ovariectomy. RAMEL was administered orally once a day in the prophylactic treatment mode for 8 weeks, 6 weeks after ovariectomy.Results: Fourteen weeks after ovariectomy, there was a significant reduction in femoral bone mineral density (BMD) (g/cm2) in the OP group compared to the control group. Compared to the OP group, RAMEL treatment significantly increased the BMD level (p<0.05). Bone matrix protein 2 (BMP2) and runt-related transcription factor 2 (RUNX2) mRNA levels were significantly lower in the OP group than in the control group (p<0.05). RUNX2 and BMP2 mRNA levels were significantly higher in the RAMEL treatment groups than in the OP group (p<0.05).Conclusion: To take advantage of the peripheral effects of melatonin, RAMEL, a peripheral melatonin agonist, can be used to prevent osteoporosis.

P.353 Peripheral melatonin levels in bipolar disorder: preliminary results of a cross-sectional analysis

Recently, correlations of different physiological processes in humans with variations in the local lunisolar gravitational tide force have been observed under highly controlled laboratory conditions. Understanding of the physical nature of this phenomenon needs a comprehensive study of its possible molecular mechanisms. One of the possible timing cues is the strong periodic variation of the emanation fields of radon-222 and its progeny produced by tidal deformations of geological environment. In the present work, we argue that this variation could induce temporal modulation of radiation-induced bystander signaling pathways associated with fundamental regulators of gene expression in the suprachiasmatic nucleus clock.

Do peripheral melatonin agonists improve bone fracture healing? The effects of agomelatine and ramelteon on experimental bone fracture

Melatonin improves fracture healing, but the long-term use of melatonin seems impracticable in the treatment of fracture due to side effects caused by hormonal stress on chronological rhythm. Ramelteon (RAMEL) and agomelatine (AGO) are non-selective peripheral melatonin receptor (MT) agonists. This study investigated the effects on bone fracture healing of these MT agonists, which do not affect the central nervous system.The rats were divided into 6 groups, including Group 1 (SHAM): sham operated group; Group 2 (FRACTURE): femoral fracture control; Group 3 (FR + AGO30): femoral fracture + agomelatine 30 mg/kg; Group 4 (FR + AGO60): femoral fracture + agomelatine 60 mg/kg; Group 5 (FR + RAMEL3): femoral fracture + ramelteon 3 mg/kg; and Group 6 (FR + RAMEL6): femoral fracture + ramelteon 6 mg/kg.After 21 days, the rats were subjected to X-ray imaging. Bone healing was evaluated with hematoxylin-eosin (HE) staining. Messenger RNA (mRNA) expressions of bone formation markers, such as bone alkaline phosphatase (ALP), osteocalcin (OC), and osteopontin (OP), were evaluated by real-time polymerase chain reaction (RT-PCR) and with immunohistochemistry (IHC) staining.The radiographic fracture healing scores were statistically significantly higher in the FR + AGO60 group and the FR + RAMEL3 group than in the FRACTURE group. The histopathology and molecular results supported the radiographic results.It was shown that agomelatine and ramelteon increase bone fracture healing, leading to the conclusion that a preference for agomelatine, an antidepressant, and ramelteon, a sleep aid, will increase bone fracture healing in patients with fractures.

Trade-off expression of melatonin receptor subtypes (Mel1a and Mel1b) and androgen receptor in lung of a tropical bird, Perdicula asiatica.

The role of circulatory steroid hormone along with melatonin in lung of any seasonally breeding bird has never been explored so far. This could be interesting because steroid hormones are immunosuppressive while melatonin is immunostimulatory in nature. In our present study, we report the effect of exogenous melatonin and testosterone on expression of melatonin receptor subtypes (Mel1a and Mel1b ) and androgen receptor in lung of a tropical bird Perdicula asiatica. Birds were collected from vicinity of Varanasi and acclimatized in laboratory with sufficient food and water. The birds were treated with melatonin and testosterone at dose of 25µg/100g B.wt./day and 1mg/100g B.wt./day, respectively, for 28days. At the end of the experiment, the birds were sacrificed and lung tissue and blood sample were collected for immunohistochemistry, Western blot analysis and hormonal assay. Testosterone treatment increased circulatory testosterone and upregulated expression of androgen receptors whereas downregulated expression of melatonin receptor subtypes Mel1a and Mel1b . Melatonin administration increased peripheral melatonin and upregulated expression of melatonin receptor subtypes Mel1a and Mel1b while downregulated androgen receptor. Thus, our results suggest that a trade-off relationship between melatonin and testosterone exists in regulation of their receptors in lung of Perdicula asiatica.

Two indoleamines are secreted from rat pineal gland at night and act on melatonin receptors but are not night hormones.

At night, the pineal gland produces the indoleamines, melatonin, N-acetylserotonin (NAS), and N-acetyltryptamine (NAT). Melatonin is accepted as a hormone of night. Could NAS and NAT serve that role too? Concentration-response measurements with overexpressed human melatonin receptors MT1 and MT2 ; mass spectrometry analysis of norepinephrine-stimulated secretions from isolated rat pineal glands; analysis of 24-hour periodic samples of rat blood. We show that NAT and NAS do activate melatonin receptors MT1 and MT2 , although with lower potency than melatonin, and that in vitro, melatonin and NAS are secreted from stimulated, isolated pineal glands in roughly equimolar amounts, but secretion of NAT was much less. All three were found at roughly equal concentrations in blood during the night. However, during the day, serum melatonin fell to very low values creating a high-amplitude circadian rhythm that was absent after pinealectomy, whereas NAS and NAT showed only small or no circadian variation. Blood levels of NAS and NAT were insufficient to activate peripheral melatonin receptors, and they were invariant, so they could not serve as circulating hormones of night. However, they could instead act in paracrine circadian fashion near the pineal gland or via other higher-affinity receptors.

The Relationship Between Daytime Salivary Melatonin and Gastrointestinal Symptoms in Young Adults Seeking Psychiatric Care.

The pathophysiology of irritable bowel syndrome (IBS) is not completely understood, although we do know that patients with IBS have a high prevalence of psychiatric comorbidity (mainly depression and anxiety disorders). Melatonin, produced in the gastrointestinal tract, influences gut motility. Psychiatric conditions are associated with circadian disturbances in peripheral melatonin levels. This study aimed to investigate associations between daytime salivary melatonin and gastrointestinal symptoms in young adult psychiatric patients. Ninety-six patients (86% women), aged 18-25 years (M (SD) = 21 (2)), seeking psychiatric care with primarily anxiety disorders, affective disorders, or both were included in the study. Total scores from the Gastrointestinal Symptoms Rating Scale - IBS were compared with salivary melatonin measured at three time points (30 minutes after waking up, at 11:00 hours and 30 minutes after lunch) during the waking hours of 1 day. After adjustment for potential confounders, melatonin levels in saliva 30 minutes after lunch remained significantly correlated to the total Gastrointestinal Symptoms Rating Scale - IBS score after correction for multiple testing (B = 0.016, SE = 0.006, p = .015, q = 0.045). In a post hoc analysis, symptoms of gastrointestinal pain and bloating contributed most to this association. In young adult psychiatric patients, salivary melatonin levels after lunch are associated with gastrointestinal symptoms, which is consistent with the proposed effect of elevated levels of gastrointestinal melatonin on gut motility. This result suggests a link between IBS symptoms and regulation of melatonin in patients with psychiatric disorders.

Associations of pineal volume, chronotype and symptom severity in adults with attention deficit hyperactivity disorder and healthy controls

The pineal gland, as part of the human epithalamus, is the main production site of peripheral melatonin, which promotes the modulation of sleep patterns, circadian rhythms and circadian preferences (morningness vs. eveningness). The present study analyses the pineal gland volume (PGV) and its association with circadian preferences and symptom severity in adult ADHD patients compared to healthy controls. PGV was determined manually using high-resolution 3T MRI (T1-magnetization prepared rapid gradient echo) in medication free adult ADHD patients (N=74) compared to healthy controls (N=86). Moreover, the Morningness–Eveningness Questionnaire (MEQ), the ADHD Diagnostic Checklist and the Wender–Utah Rating Scale were conducted. PGV differed between both groups (patients: 59.9±33.8mm3; healthy controls: 71.4±27.2mm3, P=0.04). In ADHD patients, more eveningness types were revealed (patients: 29%; healthy controls: 17%; P=0.05) and sum scores of the MEQ were lower (patients: 45.8±11.5; healthy controls 67.2±10.1; P<0.001). Multiple regression analyses indicated a positive correlation of PGV and MEQ scores in ADHD (β=0.856, P=0.003) but not in healthy controls (β=0.054, P=0.688). Patients’ MEQ scores (β=−0.473, P=0.003) were negatively correlated to ADHD symptoms. The present results suggest a linkage between the PGV and circadian preference in adults with ADHD and an association of the circadian preference to symptom severity. This may facilitate the development of new chronobiological treatment approaches for the add-on treatment in ADHD.

Photoperiodic regulation of nuclear melatonin receptor RORα in lymphoid organs of a tropical rodent Funambulus pennanti: Role in seasonal oxidative stress

The orphan nuclear receptor RORα of RZR/ROR family has been suggested to mediate the genomic actions of melatonin on the expression of antioxidant enzymes. However, no direct evidences exist. In the present study we explored the role of photoperiod (natural and artificial) in regulation of RORα and its association with the photoperiod induced antioxidant defense system in the lymphoid organs (spleen and thymus) of seasonally breeding, tropical squirrels, Funambulus pennanti. The photoperiod mediated regulation of antioxidant status was checked along with the RORα expression and circulatory melatonin level in the squirrels. The enhancement of the antioxidant capacity of serum and lymphoid organ was concomitant with the short photoperiod (10L:14D) induced high levels of plasma melatonin. Further, peripheral melatonin level enhanced the AANAT activity as well as the melatonin synthesis in the lymphoid tissues. RORα expression presented an inverse correlation with the plasma level of melatonin as well as the short day induced antioxidant enzyme activity in the lymphoid organs. The results suggest that for reduction of seasonal oxidative stress melatonin might not be utilizing the nuclear receptor RORα pathway; rather the rise in circulatory melatonin collectively with tissue specific melatonin might be protecting the splenic and thymic lymphocytes from the seasonal oxidative stress.

Age dependent nitro-oxidative load and melatonin receptor expression in the spleen and immunity of goat Capra hircus

The decline in the plasma level of melatonin has been associated with increased oxidative stress in the physiological system while aging. The increased levels of oxidants are known to augment the nitro-oxidative stress, which induces the apoptotic factors in lymphoid organs leading to age dependent immunosenescence. There are no reports to date that can suggest how the age dependent nitro-oxidative stress can influence the melatonin membrane MT1/MT2R expression and immune status of any small ruminant. In the present study, we noted the expression of melatonin receptors MT1R and MT2R and inducible nitric oxide synthase (iNOS) along with the apoptotic markers (viz. Bcl-2, Bax and Pro-caspase-3) in the spleen of young, middle-aged and old-aged Indian goat Capra hircus. The lymphocyte proliferation was also recorded along with the total nitrite and nitrate ion concentration (NOx) in the spleen and plasma. An age dependent decline in MT1R and MT2R expressions and lymphocyte proliferation with increased level of reactive nitrogen species (RNS) and iNOS expression was noted. An increased Bax/Bcl-2 ratio and a decreased Pro-caspase-3 expression were observed in the spleen of goat with an age dependent decline in the peripheral melatonin level. This decline in melatonin along with reduced melatonin receptor (MT1/MT2) expression and elevated RNS level in the spleen with aging might have an important role in the regulation of immune function of goats. Our observations suggest that the age-associated immunosenescence observed in goats can be a consequence of declining melatonin and its receptor expression and induction of apoptotic factors influenced by the increased RNS level that deteriorates the proper functioning of the spleen.

Photoperiodic induced melatonin regulates immunity and expression pattern of melatonin receptor MT1 in spleen and bone marrow mononuclear cells of male golden hamster

The pineal gland transduces day length information into chemical signal of melatonin that ultimately translates photic stimulus into season-specific immune responses to promote survival of individual from incidence of opportunistic diseases. To date, the immune adjustments being a result of photoperiodic exposures for any nocturnal seasonally breeding rodent have not been systematically examined. Therefore, we evaluated the humoral and cell mediated immune responses of photoperiodically entrained male golden hamsters. Short day induced melatonin increased the immune parameters such as spleen mass, total leukocyte (TLC) and lymphocyte count (LC), proliferation of splenocytes, peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BMMNCs) along with serum IL-2 and anti-Keyhole Limpet Hemocyanin (KLH) IgG production when compared with long day experienced hamsters. Short term melatonin treatment (for two weeks) to long day hamsters enhanced to some extent the proliferation of splenocytes, PBMC and TLC/LC. We also localized the melatonin membrane receptor MT1 in spleen and BMMNCs that strongly supported our western blot analysis for the expression of MT1 in spleen suggesting that different photoperiodically induced circulatory melatonin is responsible for the immunomodulation. Therefore, photoperiod can influence the peripheral melatonin level to improve immune responses of hamsters according to season for better survival.

Daily variations in plasma melatonin and melatonin receptor (MT1), PER1 and CRY1 expression in suprachiasmatic nuclei of tropical squirrel, Funambulus pennanti

The suprachiasmatic nucleus (SCN) plays a major role in photoperiodic regulation of seasonal functions by modulating the melatonin signal. To date no report exists regarding the role of the ambient photoperiod in the regulation of melatonin receptor MT1 and clock gene (PER1 and CRY1) expression in the SCN of any tropical rodent that experiences the least variation in the photoperiod. We noted the expression of MT1, PER1 and CRY1 in the SCN of a tropical squirrel, Funambulus pennanti, along with the plasma level of melatonin over 24h during the reproductively active (summer) and inactive (winter) phases. The seasonal day length affected the peripheral melatonin, which was inversely related with the MT1 expression in the SCN. The timing for peak expression of PER1 was the same in both phases, while the decline in PER1 expression was delayed by 4h during the inactive phase. The CRY1 peak advanced by 4h during the active phase, while the interval between the peak and decline of CRY1 remained the same in both phases. It can be suggested that seasonally changing melatonin levels modulate MT1 expression dynamics in the SCN, altering its functional state, and gate SCN molecular "clock" gene profiles through changes in PER/CRY expression. Such a regulation is important for photo-physiological adaptation (reproduction/immunity) in seasonal breeders.

Melatonin improves humoral and cell-mediated immune responses of male golden hamster following stress induced by dexamethasone

Melatonin is known as an antistress and immunostimulator compound while glucocorticoids have immunosuppressive function. The mechanism of action of both the hormones on immune cells is still a question. We found that melatonin improved the effect of dexamethasone (synthetic glucocorticoid) induced immunosuppression of splenocytes and bone marrow GM-CFU along with increased production of serum IL-2, IgG and the receptor expression for melatonin and glucocorticoid in spleen that might be responsible for the proliferation of immune cells. Thus, seasonal variation in peripheral melatonin might be responsible for the improvement of immune status under different stress conditions experienced by the rodents for better survival.

Correlation between peripheral melatonin and general immune status of domestic goat, Capra hircus: A seasonal and sex dependent variation

Caprine immune system has largely been neglected by ruminant researchers despite of its high economic importance in bioindustry. We made an attempt to note the annual/seasonal and gender dependent variation in immune status of the domestic goat, Capra hircus, Jamunapari breed and correlated with the concentration of peripheral gonadal hormones (testosterone, 17β-estradiol) and melatonin. Based on the data of general immune parameters such as total leukocyte count (TLC) and percent lymphocyte count (%LC) along with blastogenic response of splenocytes in terms of percent stimulation ratio (%SR), we found an annual variation in immune status of male, female and castrated male goats in a gender dependent manner. Female goats showed higher immune parameters than that of castrated as well as intact male goats. Testosterone in intact male goats was high throughout the year, which might be responsible for low immune status. However, in castrated male goats, plasma testosterone was undetectable and presented an immune status equivalent to that of female goats. We observed a high immune status during the winter season in all the groups of goats, which might be due to high circulatory concentration and longer duration of melatonin induced by short days. Being released by circulating lymphocytes, the concentration of interleukin-2 (IL-2) in blood plasma, showed an annual and seasonal variation being higher in female than castrated and intact male goats throughout the year, having a similar trend in plasma melatonin concentration. The higher immune status in female goats during the winter months might have helped them to overcome the winter bound stress, i.e. low temperature. Therefore, we may propose that testosterone acts as an immunosupressor while melatonin as an immunostimulator for goats as it showed a positive correlation with immune parameters noted.

Reproductive phase dependent daily variation in melatonin receptors (Mel 1a and Mel 1b), androgen receptor (AR) and lung associated immunity of Perdicula asiatica

Our knowledge about the involvement of melatonin in the regulation of lung associated immune system (LAIS) is still poor though the melatonin receptor types (Mel 1a and Mel 1b) have been localized in lungs of some wild birds. We thought to explore the correlation between daily variation (within a 24 h time scale) in peripheral melatonin and testosterone along with expression of melatonin receptors (Mel 1a and Mel 1b) and androgen receptor (AR) in lungs during reproductively active and inactive phases. Receptor expression of Mel 1b was more prominent than Mel 1a at all the time points during both the reproductive phases. The expression of AR was inversely related to both the melatonin and its receptor expression at the 24 h time scale during both the reproductive phases. Results also reflected a parallel relationship of melatonin, melatonin receptors and all the immune parameters (total leukocyte count, lymphocyte count, % stimulation ratio) suggesting that peripheral melatonin might be responsible for daily periodicity of LAIS. The presence of androgen receptors in lung led us to propose that gonadal steroid does influence the LAIS. Therefore melatonin along with testosterone might be acting as a temporal synchronizer for daily rhythms in lung associated immunity in Perdicula asiatica during different reproductive phases.

Propofol Anesthesia Significantly Alters Plasma Blood Levels of Melatonin in Rats

General anesthesia combined with surgery has been shown to decrease the nocturnal peak of melatonin in patients. However, the role of anesthesia itself on melatonin secretion remains unknown. We previously showed that anesthesia induced by propofol modifies the circadian time structure in both rats and humans and phase advances the circadian rest-activity rhythm in rats. In this study, we examined the secretion of melatonin during 24 h after a 30-min propofol anesthesia in rats. Rats were exposed to 12-h light/12-h dark alteration conditions and anesthetized with propofol (120 mg/kg intraperitoneally) around their peak of melatonin secretion (Zeitgeber time 16). Trunk blood samples were collected at seven subsequent Zeitgeber times to assess the effects of propofol on circadian melatonin secretion. Propofol modifies the peripheral melatonin by significantly decreasing its concentration ( approximately 22-28%) during the immediate 3 h after the wake up from anesthesia and then significantly increasing melatonin secretion 20 h after anesthesia ( approximately 38%). Cosinor analysis suggests that propofol induces a phase advance of the circadian secretion of peripheral melatonin. The results demonstrate the disturbing effects of propofol anesthesia on the circadian rhythm of plasma melatonin in rats under normal light conditions. These results parallel the desynchronization of the circadian rhythms of locomotor activity and temperature previously observed after propofol anesthesia.

Modulation of immunity in young-adult and aged squirrel, Funambulus pennanti by melatonin and p-chlorophenylalanine

BackgroundOur interest was to find out whether pineal gland and their by melatonin act as modulator of immunosenescence. Parachlorophenylalanine (PCPA) – a β adrenergic blocker, is known to perform chemical pinealectomy (Px) by suppressing indirectly the substrate 5-hydroxytryptamine (5-HT) for melatonin synthesis and thereby melatonin itself. The role of PCPA, alone and in combination with melatonin was recorded in immunomodulation and free radical load in spleen of young adult and aged seasonal breeder Indian palm squirrel Funambulus pennanti.ResultsAged squirrel presented reduced immune parameters (i.e. total leukocyte count (TLC), Lymphocytes Count (LC), % stimulation ratio of splenocytes (% SR) against T cell mitogen concanavalin A (Con A), delayed type hypersensitivity (DTH) to oxazolone) when compared to young adult group. Melatonin administration (25 μg/100 g body mass/day) significantly increased the immune parameters in aged more than the young adult squirrel while PCPA administration (4.5 mg/100 g body mass/day) reduced all the immune parameters more significantly in young than aged. Combination of PCPA and melatonin significantly increased the immune parameters to the normal control level of both the age groups. TBARS level was significantly high in aged than the young group. PCPA treatment increased TBARS level of young and aged squirrels both while melatonin treatment decreased it even than the controls. Nighttime peripheral melatonin level was low in control aged group than the young group. Melatonin injection at evening hours significantly increased the peripheral level of nighttime melatonin, while combined injection of PCPA and melatonin brought it to control level in both aged and young adult squirrels.ConclusionPCPA suppressed immune status more in aged than in adult by reducing melatonin level as it did chemical Px. Melatonin level decreased in control aged squirrels and so there was a decrease in immune parameters with a concomitant increase in free radical load of spleen. Decreased immune status can be restored following melatonin injection which decreased free radical load of spleen and suggest that immune organs of aged squirrels were sensitive to melatonin. Increased free radical load and decreased peripheral melatonin could be one of the reasons of immunosenescence.

Photoperiod–Testicular–Immune Interaction in a Seasonal Breeder Indian Palm Squirrel Funambulus pennanti During the Reproductively Inactive and Active Phases

The differential effect of long (LD; 16 : 8 h light/dark), short (SD; 10 : 14 h light/dark) and natural day length (NDL; 12 : 12 h light/dark) during the reproductively inactive (RIP) and active (RAP) phases was assessed in relation to immunity and reproductive function of a tropical rodent Funambulus pennanti. They presented high immunity and low testicular activity during RIP and an opposite during RAP. SD increased spleen and thymus weight, leukocyte and lymphocyte counts, cell mediated immunity [i.e. blastogenic response in terms of percentage stimulation ratio of splenocytes and thymocytes (when challenged with concanavalin A)] and delayed type hypersensitivity to oxazolone. SD during RIP increased the above mentioned parameters and reduced testes weight compared to NDL groups. During RAP, LD reduced all the immunological parameters when compared with NDL and SD experiencing groups of RIP and RAP phases. The LD group reduced the immunological parameters compared to RAP, suggesting that LD had always an inhibitory effect on immune status being independent of reproductive phases. The intensity of the stimulatory effects of SD and inhibitory effects of LD during both reproductive phases was significantly different. We exposed another set of squirrels to the above photoperiodic schedule for prolonged period (30 weeks) during RAP. A clear testicular refractoriness followed by immunorefractoriness was observed in the group experiencing SD and LD for 30 weeks. The photorefractoriness presented by the testes was inversely related to the immunorefractoriness. The peripheral melatonin level of those squirrels reflected the photoperiodic signal perceived by squirrels for immunomodulation and gonadal function, suggesting that immune system and gonadal function might have coevolved.

Effect of exogenous melatonin on X-ray induced cellular toxicity in lymphatic tissue of Indian tropical male squirrel, Funambulus pennanti

Purpose: The radioprotective ability of melatonin was investigated in the Indian tropical rodent, Funambulus pennanti during its reproductively inactive phase (RIP) when peripheral melatonin is high and the animal is under the influence of environmental stresses.Materials and methods: Fifty male squirrels were divided into two sets of 25 each; with set 1 receiving 0.9% saline and set 2 receiving 25 μg melatonin/100 g body weight/day for four weeks during evening hours. Five saline-treated and five-melatonin treated squirrels were sacrificed at times of 4, 24, 48 and 72 hours following 2.06 Gy X-ray radiation. Remaining squirrels that were not exposed to X-ray were used as control and melatonin treated, respectively. Total leukocyte count (TLC) and lymphocyte count (LC) in peripheral blood and lipid peroxidation (LPO) status, superoxide dismutase (SOD) activity, total antioxidant status (TAS), apoptotic percentage on the basis of morphological changes and DNA fragmentation and caspase-3 activity were measured in the spleens of squirrels.Results: Peripheral blood and spleens with higher intrinsic levels of environmental and X-radiation induced free radical generation had inhibited TLC, LC, SOD activity and TAS and increased LPO and apoptosis. Melatonin pre-treatment significantly reduced and altered the changes brought on by X-radiation.Conclusion: Exogenous melatonin with its anti-apoptotic and antioxidant properties additively increased the immunity of the squirrels, by protecting their hematopoietic system and lymphoid organs against X-ray radiation induced cellular toxicity.