Role of the hypothalamic suprachiasmatic nucleus in the effect of melatonin on the thymus, adrenal glands, and spleen in rats

We studied the role of the hypothalamic suprachiasmatic nucleus in realization of the effect of melatonin on stress marker organs in rats under normal conditions and during acute stress. Stress induced involution of the thymus in active rats and adrenal gland hypertrophy in active and passive animals. Electrocoagulation of the suprachiasmatic nucleus induced a more pronounced decrease in the weight of the thymus and greater increase in the weight of the adrenal glands. Melatonin administration after electrocoagulation of the suprachiasmatic nucleus had no effect on the relative weight of the thymus, adrenal glands, and spleen in control and stressed animals. The influence of melatonin on the thymus, adrenal glands, and spleen is partly mediated by this structure of the brain. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 4, pp. 364–367, April, 2006     

Comparative Analysis of the Effect of Cytokines on the Thymus,Adrenal Glands,and Spleen in Rats with Various Behavioral Characteristics

We compared the effect of a pro-inflammatory cytokine IL-1β and anti-inflammatory cytokine IL-4 on the state of stress-marker organs in rats with various behavioral characteristics in the open-field test. Intraperitoneal injection of the cytokines was followed by a slight decrease in the relative weight of the thymus, adrenal glands, and spleen in behaviorally active and, especially, in passive animals. These changes are probably associated with the effect of the test immunomodulators on apoptosis and migration of cells of the immunocompetent organs. Pretreatment with IL-1β and IL-4 was shown to prevent involution of the thymus and spleen in rats during acute stress on the model of immobilization with simultaneous electrocutaneous stimulation. Hence, these cytokines have the same effects on functional state of stressmarker organs in animals. IL-1β and IL-4 have a greater effect in passive rats than in active specimens, which reflects specific features of immune mechanisms in animals with different emotional reactivity.     

Lipid peroxidation in the brain and liver of rats during acute stress and melatonin treatment

We studied the effects of acute stress and exogenous melatonin in various doses on the intensity of lipid peroxidation in emotiogenic structures of the brain and liver of rats with different activity in the open field. Stress had no effect on the content of malonic dialdehyde in the hypothalamus, sensorimotor cortex, and liver of active and passive rats receiving physiological saline. The influence of melatonin on malonic dialdehyde content depended on the dose of this substance. The amount of malonic dialdehyde in brain structures (active and passive rats) and liver (active rats) increased after administration of exogenous melatonin in doses of 0.5 and 2 mg/kg, but decreased after treatment with the hormone in a dose of 1 mg/kg. Melatonin in various doses decreased malonic dialdehyde content in the liver of passive rats. The effects of melatonin are partly related to modulation of lipid peroxidation in central and peripheral tissues of the organism. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 7, pp. 19–23, July, 2004     

Restoration of emotional stress reactions in rats following disruption of the limbic structures of the brain by delta-sleep-inducing peptide

This report describes studies of delta-sleep-inducing peptide in the mechanism of compensating emotional behavior following disruption of a number of structures of the limbic complex (the septum and amygdala). Studies were performed in male Wistar rats. Peptide was given i.p. at a dose of 60 nmol/kg. The individual/typological characteristics of the rats' behavior and their resistance to stress was predicted using an open field test. Emotional stress was modeled by immobilizing the animals and applying electric shocks to the skin. Stress was assessed in terms of survival, adrenal hypertrophy, and thymic involution in stress conditions. Bilateral lesioning to brain structures was carried out by anodic polarization. The results obtained showed that the septum and amygdala play a significant role in the mechanisms of resistance to emotional stress. Bilateral disruption of these structures significantly decreased the animals' resistance to emotional stress, producing alterations in behavior in the open field test, increasing the lethality of acute emotional stress, and inducing changes in stress marker organs (the adrenals and thymus) in stress conditions, as compared to controls. Administration of peptide to animals with lesions to the septum or amygdala increased their resistance to emotional stress, as indicated by open field test behavior, survival, and adrenal and thymus weight in stress conditions. Thus, doses of delta-sleep-inducing peptide partially reverse reductions in stress resistance in animals with lesions to structures of the limbic complex. Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 83, No. 11-12, pp. 29–38, November–December, 1997.     

Duration dependent effect of chronic stress on primary and secondary lymphoid organs and their reversibility in rats

The present study was undertaken to investigate whether or not chronic stress effect and its reversibility on lymphoid organs is duration dependent. Male rats were exposed to restraint (1?h) followed by a gap of 4?h to forced swimming exercise (15?min) daily for 2, 4 and 8 weeks. After each exposure period, rats were allowed to recover for 6 weeks. Stress exposure resulted in duration dependent decreases in weight of thymus and axillary lymph nodes, lymphocyte counts of spleen, thymus and axillary lymph nodes and number of islets of white pulp of spleen and increases in apoptotic index of splenocytes, thymocytes and lymphocytes of axillary lymph nodes. All the parameters of lymphoid organs studied showed significant alterations in 2 weeks of stress exposure indicated their sensitivity to stress effects in short term exposure and thymus was the most sensitive organ among all. The alterations in all the parameters of spleen and majority of parameters of thymus and axillary lymph nodes returned to control level in recovery group rats of 2 and 4 weeks exposure but not in that of 8 weeks exposure. The present study for the first time reveal that severity of stress effects on lymphoid organs increases with increasing duration of exposure and shorter the exposure period faster the recovery. In addition, an in vitro study showed that corticosterone caused apoptosis of thymocytes, splenocytes and lymphocytes of axillary lymph nodes in dose dependent manner. Thus corticosterone induced death of cells of lymphoid organs under stress is the major cause of involution of lymphoid organs.     

Lipid Peroxidation in the Brain and Liver of Rats during Acute Stress and Melatonin Treatment

We studied the effects of acute stress and exogenous melatonin in various doses on the intensity of lipid peroxidation in emotiogenic structures of the brain and liver of rats with different activity in the open field. Stress had no effect on the content of malonic dialdehyde in the hypothalamus, sensorimotor cortex, and liver of active and passive rats receiving physiological saline. The influence of melatonin on malonic dialdehyde content depended on the dose of this substance. The amount of malonic dialdehyde in brain structures (active and passive rats) and liver (active rats) increased after administration of exogenous melatonin in doses of 0.5 and 2 mg/kg, but decreased after treatment with the hormone in a dose of 1 mg/kg. Melatonin in various doses decreased malonic dialdehyde content in the liver of passive rats. The effects of melatonin are partly related to modulation of lipid peroxidation in central and peripheral tissues of the organism.     

不同月龄SPF级SD雌性大鼠主要脏器参数的研究

目的：探讨SD雌性大鼠的体重、脏器重量及其指数的正常值范围。方法：选用1月龄的雌性大鼠74只,分别于2、3、4、7、8月龄时测定其体重及10个主要脏器重量,并计算其脏器指数。结果：从2月龄至8月龄,雌鼠心,肝,肾,脑,肾上腺的重量均明显增长,而胸腺重量显著降低。然而由于体重增长等因素,其心、肝、脾、肺、肾、脑、胸腺以及肾上腺等指数均明显降低。结论：SPF级SD雌性大鼠主要脏器及其指数可反映其结构变化以及生理功能状态。     

Effect of interleukin-1β on the thymus, adrenals, and spleen in august, wistar, and WAG rats in stress

Emotional stress causes a decrease in the relative mass of the thymus, adrenals, and spleen in August, Wistar, and WAG rats, which is the greatest in animals with a low motor activity in the open field test. Intraventricular administration of interleukin-1β diminishes the decrease in the relative mass of spleen in August and Wistar rats, has no significant effect on the relative mass of thymus in all rats, and leads to an increase in the relative mass of adrenals in immobilized WAG rats. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 7, pp. 32–35, July, 1997     

Effect of amitriptyline on daily variations in cell composition of immune organs in rats with experimental desynchronosis

We studied the effects of amitriptyline (preparation stimulating melatonin synthesis in the pineal gland) on daily variations of cell composition in immune organs of Wistar rats with experimental desynchronosis. Amitriptyline administered in the evening restored the daily dynamics of the number of thymus cells. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 130, No. 11, pp. 589–592, November, 2000     

Effect of ultraviolet B irradiation on immobilization stress-induced changes in the protective systems of C57Bl/6 mice

We studied the effect of ultraviolet B irradiation on superoxide dismutase activity, ceruloplasmin level in the plasma, and steroid hormone concentration in the adrenal glands of C57Bl/6 mice subjected to immobilization stress. Ultraviolet B irradiation did not abolish the increase in superoxide dismutase activity, but decreased ceruloplasmin level in the plasma and corticosteroid concentration in the adrenal glands of mice exposed to immobilization stress. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 2, pp. 180–183, February, 2006     

Quantitative interactions in weight of lymphoid organs and steroid hormonal organs in hamsters under several experimental conditions

The adrenal and gonadal steroid hormones may continue to regulate lymphoid cells in tissues of mammals throughout their life span. To examine quantitative interrelationships between the endocrine and immune systems, we measured weights of the organs and compared them. The results showed that: (1) The relative weight of the adrenals in adult male hamsters significantly exceeded that of age-matched females. The adult thymus and spleen were heavier in females. (2) Adult gonadectomy induced marked involution of the thymus and adrenal hypertrophy in both sexes. (3) A single oestrone injection at suckling has severe, long lasting effects, with gonadal atrophy and hypertrophy of lymphoid tissues in both sexes for I year. (4) Testosterone in the same way produced adrenal hypertrophy in female hamsters, and adrenal atrophy in males. (5) Thymectomy, at 3 weeks of age, resulted in marked atrophy of the gonads in late adulthood in both sexes. (6) Repeated pulses of cortisone acetate led to marked involution of the thymus and steroid organs, the adrenals and testes. The rather unexpected results, as in (2), (3) and (5), probably represent the ultimate consequence of serial interactions among these organs after treatment. These findings suggest that there is thymus-gonads interdependence even in adulthood, and that subtle counterbalancing co-operation between the adrenals and gonads may regulate lymphocyte functions in tissues. between the adrenals and gonads may regulate lymphocyte functions in tissues.     

Quantitative interactions in weight of lymphoid organs and steroid hormonal organs in hamsters under several experimental conditions.

The adrenal and gonadal steroid hormones may continue to regulate lymphoid cells in tissues of mammals throughout their life span. To examine quantitative interrelationships between the endocrine and immune systems, we measured weights of the organs and compared them. The results showed that: (1) The relative weight of the adrenals in adult male hamsters significantly exceeded that of age-matched females. The adult thymus and spleen were heavier in females. (2) Adult gonadectomy induced marked involution of the thymus and adrenal hypertrophy in both sexes. (3) A single oestrone injection at suckling has severe, long lasting effects, with gonadal atrophy and hypertrophy of lymphoid tissues in both sexes for I year. (4) Testosterone in the same way produced adrenal hypertrophy in female hamsters, and adrenal atrophy in males. (5) Thymectomy, at 3 weeks of age, resulted in marked atrophy of the gonads in late adulthood in both sexes. (6) Repeated pulses of cortisone acetate led to marked involution of the thymus and steroid organs, the adrenals and testes. The rather unexpected results, as in (2), (3) and (5), probably represent the ultimate consequence of serial interactions among these organs after treatment. These findings suggest that there is thymus-gonads interdependence even in adulthood, and that subtle counterbalancing co-operation between the adrenals and gonads may regulate lymphocyte functions in tissues. between the adrenals and gonads may regulate lymphocyte functions in tissues.     

Morphological changes in immune and endocrine organs of stressed mice after administration of a gonadotropin-releasing hormone analogue

Administration of Surfagon, a gonadotropin-releasing hormone analogue, in doses of 0.1 and 5.0 μg/kg before emotional nociceptive stress increased lymphocyte migration from the thymus, decreased the volume of lymphoid tissue in the spleen and thymus, reduced the width of the zona fasciculata and increased the width of the zona glomerulosa in the adrenal cortex of male CBA mice. These effects of the peptide persisted in castrated animals. Surfagon prevented stress-induced activation of the adrenal glands and accidental transformation of the thymus and spleen in castrated animals. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 11, pp. 590–593, November, 2007     

Effect of Low-Choline Diet and Ethanol on Electroconductivity of Tissues in CBA Mice

We studied electrophysiological parameters and morphological changes in the adrenal glands and spleen of CBA mice feeding a low-choline diet and/or ethanol-containing diet. The polarization coefficient underwent similar changes in the adrenal glands and spleen, which was associated with different contribution of impedance frequency components. Morphological changes in the adrenal glands were more pronounced than in the spleen and consisted in delipidation of the adrenocortical cell cytoplasm in the zona fasciculata and increase in cell heterogeneity in the zona reticularis of animals of different groups. The observed morphological and electrophysiological changes can serve as a criterion of the severity of stress. The method for a quantitative study of tissue electroconductivity is informative for evaluation of the effects of internal and external factors on organs and tissues. __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 140, No. 11, pp. 515–518, November, 2005     

Arthritis Induced by Adjuvant in Spontaneously Hypertensive and Normotensive Rats: Endogenous Glucocorticoid Effects on Inflammatory Response

The present study investigated arthritis induced by complete Freund adjuvant (AIA) in spontaneously hypertensive and normotensive rats (respectively, SHR and NTR rats). The inflammatory reaction was studied for 28 days by evaluating paw edema and secondary lesions found 10 days after complete Freund adjuvant (CFA) administration. The body weight of the animals and macroscopic alterations of several organs, including spleen, thymus, adrenal glands, and lymph nodes, were also analyzed. The results showed that the AIA manifestations were decreased in SHRs compared with NTRs. Moreover, this altered inflammatory response was not modified by surgical adrenalectomy.     

Melatonin and Androgen Receptor Expression Interplay Modulates Cell‐Mediated Immunity in Tropical Rodent Funambulus pennanti: An In‐Vivo and In‐Vitro Study

An inverse relation exists between melatonin and androgen in most of the seasonally breeding rodents, but the regulation of their receptors in modulation of immune function has never been reported. The present study accessed the expression pattern of melatonin receptor types (mt1R & mt2R), immune parameters (lymphoid organs weight, leucocyte count, delayed type hypersensitivity and lymphocyte proliferation) in spleen and thymus whereas androgen receptor (AR) expression in thymus of Funambulus pennanti during reproductively active phase. In‐vivo melatonin treatment (Mel) and castration (Cx) significantly increased mt1R expression, immune parameters in spleen and thymus but decreased AR expression in thymus only when compared with sham control (Con) squirrels as AR expression was not observed in spleen. Mel alone or in combination with testosterone (T) to Cx squirrels significantly increased mt1R expression, immune parameters in spleen and thymus but decreased AR expression in thymus. T alone in Cx squirrels significantly decreased mt1R expression, immune parameters in spleen and thymus but increased thymic AR expression significantly. In‐vitro thymocyte culture supported our in‐vivo findings. Mel significantly increased mt1R expression, lymphocyte proliferation, IL‐2 secretion but decreased AR expression. T alone significantly decreased aforementioned three parameters but increased AR expression. Combined treatment of Mel and T bring back all parameters to control level. Though we found high mt2R expression, but no significant change has been observed. Thus, present study suggests a clear‐cut trade‐off relation between mt1R and AR expression that might be acting as an important mediator in seasonal adjustment of immune function in tropical rodents.     

Extrapineal melatonin and its role in the neuroendocrine regulation of homeostasis

The hormone of melatonin is the main regulator of biological rhythms. It was first found in the pineal gland in 1958. Melatonin is involved in the regulation of many vital physiological processes: maturation and development of genitalias, metabolism of pigments and free radicals, immune response, mood and sleep, and cell proliferation and differentiation. The pineal gland is not the only organ synthesizing melatonin. Extrapineal melatonin is widely dis-tributed in humans and animals. Melatonin-producing cells are found in the gastrointestinal and respiratory tracts, pancreas, adrenal and thyroid glands, thymus, cerebellum, urogenital system, placenta, and other organs. Melatonin is intensely synthesized in non-endocrine cells: mast cells, natural killers, eosinophilic leukocytes, platelets, and endotheliocytes. Such a wide distribution of melatonin reflects its key role as an intercellular neuroendocrine regulator and coordinator of many complex and interrelated biological processes. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 4, pp. 364–730, April, 1999     

Dynamics of morphofunctional changes in immune organs of BALB/c mice with experimental hepatitis

The time course of morphofunctional changes in the liver, thymus, and spleen was observed in BALB/c mice with Con A-induced experimental hepatitis. The progress of alterative changes in the liver was paralleled by intensification of accidental involution of the thymus. On day 1 of hepatitis development high proliferative and cytostatic activity of splenocytes was paralleled by hemorrhagic necroses and depletion of the periarteriolar lymphoid sheaths in the spleen (T-zones), presumably due to migration of activated lymphocytes to the liver and barrier tissues. Later normalization of lymphocyte proliferative activity was paralleled by recovery and hyperplasia of the splenic T-cell zones. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 4, pp. 451–454, April, 2006     

New data on the involvement of ectodermal epithelium in extrathymic differentiation of human T-lymphocytes

Thymalin accumulates only in young cells of the skin ectodermal epithelium and mucosa of the anterior portions of the digestive and respiratory systems. After appearance of keratin the cells no longer accumulate thymalin. Similarly as in the thymus, thymalin content in the ectodermal epithelium of the organs is subjected to age-associated involution. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 8, pp. 221–224, August, 2004     

Melatonin rejuvenates degenerated thymus and redresses peripheral immune functions in aged mice

The effect of melatonin on age-related thymic involution and peripheral immune dysfunctions was investigated. Exogenous melatonin was administered through the drinking water (15 microg/ml) of 22-month-old female C57BL mice for 60 consecutive days. Our results show that melatonin distinctly reversed the age-related thymic involution as revealed by the notable increase of thymus weight, total number of thymocytes and percentage of thymocytes at G2+S phases. More strikingly, spleen weight, total number of splenocytes and some peripheral immune capacity such as mitogen responsiveness and NK cell activity were also significantly recovered by 60 days of melatonin application in aged mice. Our findings demonstrate that even when the melatonin supplementation begins late in life, the age-related thymic involution and peripheral immune dysfunctions can be restored at least partially in old mice.