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Nishikant K. Subhedar - One of the best experts on this subject based on the ideXlab platform.
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Effect of alpha-melanocyte stimulating Hormone on locomotor recovery following spinal cord injury in mice: Role of serotonergic system.
Neuropeptides, 2010Co-Authors: Ashish P. Bharne, Dadasaheb M. Kokare, Manoj A. Upadhya, Nishikant K. SubhedarAbstract:Abstract The present study underscores the effect of serotonergic antagonist on alpha-melanocyte stimulating Hormone (α-MSH) induced neuronal regeneration. Swiss-albino mice were subjected to experimental spinal cord injury (ESCI) and treated with serotonergic antagonist, ritanserin, alone or in combination with α-MSH, and the locomotor recovery was investigated. ESCI was induced at thoracic T 10–12 level by compression method. Motor function score (0–10) of each mouse was monitored prior to, and on days 1, 4, 7, 10 and 14 following ESCI. Untreated ESCI animals showed almost normal hind limb motor function by 14days. Similar degree of recovery was observed on day 10 in animals given α-MSH or ritanserin. However, in animals treated with both agents, comparable recovery was observed on day 4. While histological examination of the spinal cord following ESCI showed demyelination, necrosis and cyst formation, treatment with ritanserin, alone and in combination with α-MSH, significantly prevented the tissue damage. We suggest that early antagonism of serotonergic 5-HT 2a/2c receptors may potentiate the neurotropic and locomotor recovery activity of α-MSH.
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Alpha-melanocyte stimulating Hormone antagonizes antidepressant-like effect of neuropeptide Y in Porsolt's test in rats.
Pharmacology Biochemistry and Behavior, 2006Co-Authors: Sameer N. Goyal, Dadasaheb M. Kokare, Chandrabhan T. Chopde, Nishikant K. SubhedarAbstract:Abstract The physiological and functional interaction between neuropeptide Y (NPY) and alpha-melanocyte stimulating Hormone (α-MSH) with reference to anxiety and food intake is well documented. An attempt has been made to study the influence of melanocortin (MC) system on NPY induced antidepressant-like effect in rats using Porsolt's forced swim test as the behavioral paradigm. NPY (0.40–2.10 ng/rat), NPY Y1 and Y5 receptors agonist [Leu 31 , Pro 34 ]-NPY (0.20–0.60 ng/rat) or selective MC4 receptors antagonist HS014 (0.01–0.07 ng/rat) dose dependently elicited antidepressant-like effect. On the other hand, α-MSH (100–400 ng/rat) resulted in high immobility suggestive of depression. Antidepressant-like effect of NPY (1.00–2.10 ng/rat) or [Leu 31 , Pro 34 ]-NPY (0.40–0.60 ng/rat) was significantly reversed by prior treatment of α-MSH (100 ng/rat). While antidepressant action of NPY (0.40–1.00 ng/rat) or [Leu 31 , Pro 34 ]-NPY (0.20–0.40 ng/rat) was enhanced by concurrent administration of HS014 (0.01 ng/rat), the locomotor activity in all the treatment groups was unaffected. These results suggest the possibility that MC and NPYergic systems may interact and regulate the depression via MC4 and NPY Y1 or Y5 receptors.
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GABAergic agents prevent alpha-melanocyte stimulating Hormone induced anxiety and anorexia in rats
Pharmacology Biochemistry and Behavior, 2003Co-Authors: T.lakshmi Rao, Dadasaheb M. Kokare, Sumit Sarkar, Rahul T. Khisti, Chandrabhan T. Chopde, Nishikant K. SubhedarAbstract:Abstract Alpha-melanocyte stimulating Hormone (α-MSH) is a hypothalamic peptide believed to play a tonic inhibitory role in feeding and energy homeostasis. Systemic administration of α-MSH is known to produce anorexia and anxiety. Since synaptic contacts between gamma-aminobutyric acid (GABA)ergic terminals and α-MSH neurons in the hypothalamus have been reported, the present work was undertaken to refine our knowledge on the role of GABAergic systems in anxiety and anorexia induced by intracerebroventricular (icv) administration of α-MSH in rats. The anxiety was assessed by elevated plus maze, and spontaneous food consumption was monitored during dark cycle. Prior administration of diazepam and muscimol that promote the function of GABA A receptors reversed the anxiogenic response and decreased food intake elicited by α-MSH. In contrast, bicuculline, the GABA A receptor antagonist, not only enhanced the effects of α-MSH but also prevented the influence of GABAergic drugs on α-MSH-induced anorexia and anxiety. These findings suggest that α-MSH-induced anxiety and anorexia are due to its negative influence on GABAergic system.
Dadasaheb M. Kokare - One of the best experts on this subject based on the ideXlab platform.
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Adolescent Alcohol Exposure-Induced Changes in Alpha-Melanocyte Stimulating Hormone and Neuropeptide Y Pathways via Histone Acetylation in the Brain During Adulthood.
International Journal of Neuropsychopharmacology, 2017Co-Authors: Dadasaheb M. Kokare, Evan J. Kyzar, Huaibo Zhang, Amul J. Sakharkar, Subhash C. PandeyAbstract:Background Adolescent intermittent ethanol exposure causes long-lasting alterations in brain epigenetic mechanisms. Melanocortin and neuropeptide Y signaling interact and are affected by ethanol exposure in the brain. Here, the persistent effects of adolescent intermittent ethanol on alpha-melanocyte stimulating Hormone, melanocortin 4 receptor, and neuropeptide Y expression and their regulation by histone acetylation mechanisms were investigated in adulthood. Methods Male rats were exposed to adolescent intermittent ethanol (2 g/kg, i.p.) or volume-matched adolescent intermittent saline from postnatal days 28 to 41 and allowed to grow to postnatal day 92. Anxiety-like behaviors were measured by the elevated plus-maze test. Brain regions from adult rats were used to examine changes in alpha-melanocyte stimulating Hormone, melanocortin 4 receptor, and neuropeptide Y expression and the histone acetylation status of their promoters. Results Adolescent intermittent ethanol-exposed adult rats displayed anxiety-like behaviors and showed increased pro-opiomelanocortin mRNA levels in the hypothalamus and increased melanocortin 4 receptor mRNA levels in both the amygdala and hypothalamus compared with adolescent intermittent saline-exposed adult rats. The alpha-Melanocyte stimulating Hormone and melanocortin 4 receptor protein levels were increased in the central and medial nucleus of the amygdala, paraventricular nucleus, and arcuate nucleus of the hypothalamus in adolescent intermittent ethanol-exposed compared with adolescent intermittent saline-exposed adult rats. Neuropeptide Y protein levels were decreased in the central and medial nucleus of the amygdala of adolescent intermittent ethanol-exposed compared with adolescent intermittent saline-exposed adult rats. Histone H3K9/14 acetylation was decreased in the neuropeptide Y promoter in the amygdala but increased in the melanocortin 4 receptor gene promoter in the amygdala and the melanocortin 4 receptor and pro-opiomelanocortin promoters in the hypothalamus of adolescent intermittent ethanol-exposed adult rats compared with controls. Conclusions Increased melanocortin and decreased neuropeptide Y activity due to changes in histone acetylation in emotional brain circuitry may play a role in adolescent intermittent ethanol-induced anxiety phenotypes in adulthood.
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Effect of alpha-melanocyte stimulating Hormone on locomotor recovery following spinal cord injury in mice: Role of serotonergic system.
Neuropeptides, 2010Co-Authors: Ashish P. Bharne, Dadasaheb M. Kokare, Manoj A. Upadhya, Nishikant K. SubhedarAbstract:Abstract The present study underscores the effect of serotonergic antagonist on alpha-melanocyte stimulating Hormone (α-MSH) induced neuronal regeneration. Swiss-albino mice were subjected to experimental spinal cord injury (ESCI) and treated with serotonergic antagonist, ritanserin, alone or in combination with α-MSH, and the locomotor recovery was investigated. ESCI was induced at thoracic T 10–12 level by compression method. Motor function score (0–10) of each mouse was monitored prior to, and on days 1, 4, 7, 10 and 14 following ESCI. Untreated ESCI animals showed almost normal hind limb motor function by 14days. Similar degree of recovery was observed on day 10 in animals given α-MSH or ritanserin. However, in animals treated with both agents, comparable recovery was observed on day 4. While histological examination of the spinal cord following ESCI showed demyelination, necrosis and cyst formation, treatment with ritanserin, alone and in combination with α-MSH, significantly prevented the tissue damage. We suggest that early antagonism of serotonergic 5-HT 2a/2c receptors may potentiate the neurotropic and locomotor recovery activity of α-MSH.
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Alpha-melanocyte stimulating Hormone antagonizes antidepressant-like effect of neuropeptide Y in Porsolt's test in rats.
Pharmacology Biochemistry and Behavior, 2006Co-Authors: Sameer N. Goyal, Dadasaheb M. Kokare, Chandrabhan T. Chopde, Nishikant K. SubhedarAbstract:Abstract The physiological and functional interaction between neuropeptide Y (NPY) and alpha-melanocyte stimulating Hormone (α-MSH) with reference to anxiety and food intake is well documented. An attempt has been made to study the influence of melanocortin (MC) system on NPY induced antidepressant-like effect in rats using Porsolt's forced swim test as the behavioral paradigm. NPY (0.40–2.10 ng/rat), NPY Y1 and Y5 receptors agonist [Leu 31 , Pro 34 ]-NPY (0.20–0.60 ng/rat) or selective MC4 receptors antagonist HS014 (0.01–0.07 ng/rat) dose dependently elicited antidepressant-like effect. On the other hand, α-MSH (100–400 ng/rat) resulted in high immobility suggestive of depression. Antidepressant-like effect of NPY (1.00–2.10 ng/rat) or [Leu 31 , Pro 34 ]-NPY (0.40–0.60 ng/rat) was significantly reversed by prior treatment of α-MSH (100 ng/rat). While antidepressant action of NPY (0.40–1.00 ng/rat) or [Leu 31 , Pro 34 ]-NPY (0.20–0.40 ng/rat) was enhanced by concurrent administration of HS014 (0.01 ng/rat), the locomotor activity in all the treatment groups was unaffected. These results suggest the possibility that MC and NPYergic systems may interact and regulate the depression via MC4 and NPY Y1 or Y5 receptors.
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GABAergic agents prevent alpha-melanocyte stimulating Hormone induced anxiety and anorexia in rats
Pharmacology Biochemistry and Behavior, 2003Co-Authors: T.lakshmi Rao, Dadasaheb M. Kokare, Sumit Sarkar, Rahul T. Khisti, Chandrabhan T. Chopde, Nishikant K. SubhedarAbstract:Abstract Alpha-melanocyte stimulating Hormone (α-MSH) is a hypothalamic peptide believed to play a tonic inhibitory role in feeding and energy homeostasis. Systemic administration of α-MSH is known to produce anorexia and anxiety. Since synaptic contacts between gamma-aminobutyric acid (GABA)ergic terminals and α-MSH neurons in the hypothalamus have been reported, the present work was undertaken to refine our knowledge on the role of GABAergic systems in anxiety and anorexia induced by intracerebroventricular (icv) administration of α-MSH in rats. The anxiety was assessed by elevated plus maze, and spontaneous food consumption was monitored during dark cycle. Prior administration of diazepam and muscimol that promote the function of GABA A receptors reversed the anxiogenic response and decreased food intake elicited by α-MSH. In contrast, bicuculline, the GABA A receptor antagonist, not only enhanced the effects of α-MSH but also prevented the influence of GABAergic drugs on α-MSH-induced anorexia and anxiety. These findings suggest that α-MSH-induced anxiety and anorexia are due to its negative influence on GABAergic system.
K Namba - One of the best experts on this subject based on the ideXlab platform.
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In vitro induction of CD25+ CD4+ regulatory T cells by the neuropeptide alpha-melanocyte stimulating Hormone (alpha-MSH).
Immunology & Cell Biology, 2001Co-Authors: Aw Taylor, K NambaAbstract:Top of pageAbstract Recently, we have found that the neuropeptide alpha-melanocyte stimulating Hormone (-MSH) not only suppresses IFN- production, but also induces TGF-1 production by activated effector T cells. These -MSH- treated effector T cells function as regulatory T cells in that they suppress IFN- production and hypersensitivity mediated by other effector T cells. Experimental autoimmune uveoretinitis (EAU) was suppressed in its severity and incidence in mice that were injected with primed T cells activated in vitro by APC and antigen in the presence of -MSH. Moreover, it appeared that -MSH had converted a population of effector T cells polarized to mediate hypersensitivity into a population of T cells that now mediated immunoregulation. To characterize these -MSH- treated T cells, primed T cells were TCR-stimulated in the presence of -MSH in vitro and their lymphokine profile was examined. Such effector T cells displayed enhanced levels of TGF-1 production and no IFN- or IL-10, with IL-4 levels remaining unchanged in comparison with inactivated T cells. In addition, if soluble TGF- receptor II was added to cocultures of -MSH-treated T cells and activated Th1 cells, the -MSH-treated T cells could not suppress IFN- production by the Th1 cells. These results suggest that -MSH induces T cells with a regulatory lymphokine pattern, and that through their production of TGF-1 these cells suppress other effector T cells. Examination of the -MSH-treated T cells showed that -MSH did not alter the phosphorylation of CD3 molecules following TCR engagement. Primed T cells express the melanocortin 5 receptor (MC5r), a receptor that is linked to an intracellular signalling pathway shared by other cytokine receptors. Blocking the receptor with antibody prevented -MSH from suppressing IFN- production by the activated regulatory T cells, suggesting that -MSH immunoregulation is through the MC5r on primed T cells. Surface staining and cell sorting of the -MSH- treated primed T cells showed that the regulatory T cells are CD25+ CD4+ T cells. From these results we find that -MSH can mediate the induction of CD25+ CD4+ regulatory T cells. These regulatory T cells require specific antigen for activation, but through non-specific TGF-1-mediated mechanisms they can suppress other effector T cells. Keywords: alpha-melanocyte stimulating Hormone, CD25 T cells, melanocortin 5 receptor, neuroimmunomodulation, regulatory T cells
Thomas A. Luger - One of the best experts on this subject based on the ideXlab platform.
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The human basophil – a novel target of the neuropeptide alpha‐melanocyte‐stimulating Hormone
Experimental Dermatology, 2008Co-Authors: Michael R. R. Böhm, Ulrike Raap, Thomas E. Scholzen, M. Mertens, Randolf Brehler, Alexander Kapp, Thomas A. LugerAbstract:There is increasing evidence that the basophil does not only play an important role in acute allergic reactions but also in the pathogenesis of chronic allergic disorders. Here we show that human basophils express melanocortin receptors (MC-Rs) and respond to Alpha-Melanocyte-Stimulating Hormone (alpha-MSH) with regulation of proallergic cytokine expression and modulation of basophil activation markers. Using primers against all known MC-R subtypes we demonstrate that the human basophil cell line KU812 expresses MC-1R. Expression of MC-1R on the surface of KU812 cells was confirmed by FACS analysis using an anti-MC-1R antibody. The MC-1R expressed by KU812 cells was functionally active as alpha-MSH induced intracellular cAMP in a dose-dependent manner. Moreover, alpha-MSH abrogated the effect of calcium ionophore A23187 on IL-4 mRNA expression in these cells. The relevance of the above findings was corroborated by showing that MC-1R surface expression is also detectable in basophils of leukocyte suspensions derived from whole human blood. Most interestingly, alpha-MSH was capable of suppressing the inductive effect of fMLP on surface expression of the basophil activation marker CD63 in leukocyte suspensions of atopic individuals. Likewise, alpha-MSH significantly blocked grass pollen-induced up-regulation of CD63 in leukocyte suspensions of patients with grass pollen allergy. Our findings highlight a novel functional dimension of alpha-MSH. In addition, MSH peptides may become a novel future therapeutic avenue in treating human allergic diseases.
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Failure of alpha-melanocyte stimulating Hormone to attenuate cerebral complications in experimental pneumococcal meningitis
Journal of Neuroimmunology, 2001Co-Authors: Stefan Kastenbauer, Uwe Koedel, T. Brzoska, Thomas A. Luger, H. W. PfisterAbstract:Abstract Alpha-Melanocyte-Stimulating Hormone (α-MSH) is an endogenous neuroimmunomodulatory peptide that can inhibit a broad range of inflammatory mediators known to be involved in the pathophysiology of bacterial meningitis. We evaluated the effect of α-MSH in a rat model of pneumococcal meningitis. Rats were intracisternally infected with Streptococcus pneumoniae and treatment was started 6 h after infection. Both systemic and intracisternal α-MSH failed to influence blood–brain barrier disruption, increased intracranial pressure, brain cytokine concentrations (IL-1β, IL-6, TNF-α, MIP-2, and IL-10), CSF bacterial titers, and clinical parameters of disease severity (weight loss, body temperature, and blood pressure), although the treatment strongly increased the CNS concentrations of α-MSH. However, systemic but not intracisternal α-MSH slightly reduced the CNS leukocyte accumulation, indicating that leukocyte extravasation is inhibited by α-MSH from the blood side. Our results show that α-MSH reduces the CNS leukocyte accumulation by its systemic action, but does not attenuate meningitis-associated intracranial complications.
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Alpha-Melanocyte-Stimulating Hormone induces hapten-specific tolerance in mice.
Journal of immunology (Baltimore Md. : 1950), 1996Co-Authors: Stephan Grabbe, Ranjit Bhardwaj, Karsten Mahnke, Manuel M. Simon, Thomas Schwarz, Thomas A. LugerAbstract:Alpha-Melanocyte-Stimulating Hormone (alpha-MSH) is a proopiomelanocortin-derived peptide with known immunoregulatory effects, acting mainly via modulation of cytokine secretion by lymphocytes and monocytes. When applied epicutaneously, alpha-MSH inhibits both induction as well as elicitation of contact hypersensitivity (CHS) responses in mice. We questioned whether systemically administered alpha-MSH leads to the induction of hapten-specific tolerance. For this purpose, mice were injected i.v. with 75 microgram/kg synthetic bioactive alpha-MSH 2 h before sensitization (day 0) or challenge (day 6) with the hapten, trinitrochlorobenzene (TNCB). Intravenous administration of alpha-MSH 2 h before sensitization or 2 h before challenge resulted in a markedly reduced CHS response. To distinguish between unresponsiveness and tolerance, these mice were sensitized and challenged a second time, but in the absence of alpha-MSH. Mice that had been injected with alpha-MSH before the first sensitization (day 0), but not before challenge (day 6), were also unable to develop a significant CHS response after an additional sensitization and challenge with the same Ag 10 to 14 days later. In contrast, sensitization to the unrelated hapten, dinitrofluorobenzene, was unaffected in these mice, indicating the induction of hapten-specific tolerance by alpha-MSH. Moreover, regional lymph node cells obtained from alpha-MSH-treated mice 5 days after resensitization failed to produce IL-2 in response to trinitrobenzosulfonic acid, the water-soluble analogue of TNCB, whereas lymph node cells from TNCB-sensitized, not alpha-MSH-treated, mice as well as from mice treated with alpha-MSH before challenge readily exhibited trinitrobenzosulfonic acid-specific IL-2 production in this assay. Finally, in vivo tolerance induction by alpha-MSH could be abrogated by the administration of anti-IL-10 Ab at the site of sensitization. These data indicate that alpha-MSH, in addition to its suppressive effect on induction and elicitation of CHS, is able to induce hapten-specific tolerance in mice. Thus, alpha-MSH may be a significant regulatory mediator of cutaneous immune responses in vivo.
Barbara A. Gilchrest - One of the best experts on this subject based on the ideXlab platform.
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Alpha-melanocyte stimulating Hormone-induced pigmentation is blocked by depletion of protein kinase C.
Experimental Cell Research, 1996Co-Authors: Hee-young Park, Vladimir Russakovsky, Esther Fernandez, Barbara A. GilchrestAbstract:We have explored the role of protein kinase C (PKC) in pigmentation induced by alpha-melanocyte stimulating Hormone (alpha-MSH). Using the well-studied S91 Cloudman mouse melanoma model system in which 10(-7) M alpha-MSH is known to produce a time-dependent increase in pigmentation, we found an increase in the activity of tyrosinase, the key enzyme in pigmentation, between Days 2 and 6 accompanied by an increase in mRNA and protein levels of tyrosinase, as well as an increase in the level of specifically the beta isoform of PKC. When S91 cells were treated with phorbol dibutyrate, 95% of PKC activity was lost within 48 h and the alpha-MSH-induced melanogenesis was completely blocked, as was the induction of tyrosinase mRNA and protein. Serially passaged S91 cells no longer capable of responding to alpha-MSH had an undetectable level of PKC-beta, although the tyrosinase protein level was identical to that of alpha-MSH-responsive cells. Furthermore, in these S91 cells alpha-MSH also did not increase the level of tyrosinase mRNA. Thus, induction of murine melanogenesis by alpha-MSH involves up-regulation of tyrosinase mRNA and protein mediated in part by the PKC-dependent pathway, associated with an up-regulation of the beta isoform previously demonstrated to specifically activate tyrosinase in human melanocytes.