{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T12:11:28Z","timestamp":1794485488481,"version":"4.9.1"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Immun Ageing"],"published-print":{"date-parts":[[2009,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Our interest was to find out whether pineal gland and their by melatonin act as modulator of immunosenescence. Parachlorophenylalanine (PCPA) \u2013 a \u03b2 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<jats:italic>Funambulus pennanti<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Aged 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 \u03bcg\/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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>PCPA 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.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1742-4933-6-5","type":"journal-article","created":{"date-parts":[[2009,4,23]],"date-time":"2009-04-23T18:32:15Z","timestamp":1240511535000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Modulation of immunity in young-adult and aged squirrel, Funambulus pennanti by melatonin and p-chlorophenylalanine"],"prefix":"10.1186","volume":"6","author":[{"given":"Seema","family":"Rai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandana","family":"Haldar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2009,4,23]]},"reference":[{"key":"65_CR1","first-page":"465","volume":"63","author":"GJM Maestroni","year":"1988","unstructured":"Maestroni GJM, Conti A, Pierpaoli W: Role of the pineal gland in immunity. III, Melatonin antagonizes the immunosuppressive effect of acute stress via an opiatergic mechanism. Immunology. 1988, 63: 465-469.","journal-title":"Immunology"},{"key":"65_CR2","first-page":"289","volume-title":"Melatonin Biosynthesis, Physiological effect and clinical applications","author":"GJM Maestroni","year":"1993","unstructured":"Maestroni GJM, Conti A: Melatonin in relation to the immune system. Melatonin Biosynthesis, Physiological effect and clinical applications. Edited by: Yu HS, Reiter RJ. 1993, Boca Raton, CRC Press, 289-310."},{"key":"65_CR3","doi-asserted-by":"publisher","first-page":"167","DOI":"10.2174\/1568026023394335","volume":"2","author":"JM Guerrero","year":"2002","unstructured":"Guerrero JM, Reiter RJ: Melatonin immune system relationship. Curr Top Med Chem. 2002, 2: 167-179. 10.2174\/1568026023394335.","journal-title":"Curr Top Med Chem"},{"key":"65_CR4","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1210\/endo-109-4-1295","volume":"109","author":"RJ Reiter","year":"1981","unstructured":"Reiter RJ, Craft CM, Johnson JE, King TS, Richardson BA, Vaughan GM, Vaughan MK: Age-associated reduction in nocturnal pineal melatonin levels in female rats. Endocrinology. 1981, 109: 1295-1297.","journal-title":"Endocrinology"},{"key":"65_CR5","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1073\/pnas.91.2.787","volume":"91","author":"W Pierpaoli","year":"1992","unstructured":"Pierpaoli W, Regelson W: Pineal control of aging: Effect of melatonin and pineal grafting on aging mice. Proc Natl Acad Sci USA. 1992, 91: 787-791. 10.1073\/pnas.91.2.787.","journal-title":"Proc Natl Acad Sci USA"},{"key":"65_CR6","first-page":"183","volume":"23","author":"sj Liu","year":"2002","unstructured":"Liu sj, Wang ZJ: Alzheimer-like tau phosphorylation induced by wortmannin in vivo and its attenuation by melatonin. Acta Pharmacol Sin. 2002, 23: 183-187.","journal-title":"Acta Pharmacol Sin"},{"key":"65_CR7","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1016\/j.it.2004.05.006","volume":"25","author":"G Pawelec","year":"2004","unstructured":"Pawelec G, Akbar A, Caruso C, Effros R, Grubeck-Loebenstein B, Wikby A: Is Immunosenescence infectious?. Trends Immunol. 2004, 25: 406-410. 10.1016\/j.it.2004.05.006.","journal-title":"Trends Immunol"},{"key":"65_CR8","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1111\/j.1474-9728.2004.00109.x","volume":"3","author":"W Arlt","year":"2004","unstructured":"Arlt W, Hewison M: Hormones and immune function: implications of aging. Aging Cell. 2004, 3: 209-216. 10.1111\/j.1474-9728.2004.00109.x.","journal-title":"Aging Cell"},{"key":"65_CR9","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.it.2004.02.001","volume":"25","author":"RJ Nelson","year":"2004","unstructured":"Nelson RJ: Seasonal immune function and sickness responses. Trends Immunol. 2004, 25: 187-192. 10.1016\/j.it.2004.02.001.","journal-title":"Trends Immunol"},{"key":"65_CR10","first-page":"319","volume":"136","author":"S Rai","year":"2003","unstructured":"Rai S, Haldar C: Pineal Control of immune status and hematological changes in blood and bone marrow of male squirrels (Funambulus pennanti) during their reproductively inactive phase. Comp Biochemistry and Physiology (C). 2003, 136: 319-328.","journal-title":"Comp Biochemistry and Physiology (C)"},{"key":"65_CR11","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/S0079-6123(08)62349-3","volume":"91","author":"C Haldar","year":"1991","unstructured":"Haldar C, Haussler D, Gupta D: Response of colony forming units for granulocyte macrophages (CFU-GM) of intact and pinealectomized rat bone marrow cells to murine recombinant interleukin-3 (rIL-3), recombinant granulocyte macrophage colony stimulating factor (rGM-CSF) and human recombinant erythropoietin (rEPO). Prog Brain Res. 1991, 91: 323-325.","journal-title":"Prog Brain Res"},{"key":"65_CR12","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1111\/j.1600-079X.1992.tb00030.x","volume":"12","author":"C Haldar","year":"1992","unstructured":"Haldar C, Haussler D, Gupta D: Effect of the pineal gland on circadian rhythmicity of colony forming units for granulocytes and macrophages (CFU-GM) from rat bone marrow cell cultures. J Pineal Res. 1992, 12: 79-83. 10.1111\/j.1600-079X.1992.tb00030.x.","journal-title":"J Pineal Res"},{"key":"65_CR13","first-page":"285","volume":"38","author":"J Marco","year":"1982","unstructured":"Marco J, Rosero O, Villa I, Esquifino A, Larralde J: Effect of p-chlorophenylalanine on LH, FSH, prolactin and ovulation in the rat. Rev Esp Fisiol. 1982, 38: 285-290.","journal-title":"Rev Esp Fisiol"},{"key":"65_CR14","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/0006-8993(87)90883-3","volume":"426","author":"JL Steinman","year":"1987","unstructured":"Steinman JL, Carlton SM, Haber B, Willis WD: Differential effects of p-chlorophenylalanine on indoleamines in brainstem nuclei and spinal cord of rats. I. Biochemical and behavioral analysis. Brain Res. 1987, 426: 297-309. 10.1016\/0006-8993(87)90883-3.","journal-title":"Brain Res"},{"key":"65_CR15","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1242\/jeb.199.4.793","volume":"199","author":"A Ramachandran","year":"1996","unstructured":"Ramachandran A, Patel M, Patel C: Effects of pineal indoles and parachlorophenylalanine on seasonal reproduction in the pigeon. J Exp Biol. 1996, 199: 793-800.","journal-title":"J Exp Biol"},{"key":"65_CR16","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/0014-2999(85)90758-7","volume":"111","author":"JR Ieni","year":"1985","unstructured":"Ieni JR, Thurmond JB: Maternal aggression in mice: effects of treatments with PCPA, 5-HTP and 5-HT receptor antagonists. Eur J Pharmacol. 1985, 111: 211-220. 10.1016\/0014-2999(85)90758-7.","journal-title":"Eur J Pharmacol"},{"key":"65_CR17","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/S0168-0102(98)00034-0","volume":"31","author":"K Nakajima","year":"1998","unstructured":"Nakajima K, Matsuyama K, Mori S: Prenatal administration of para-chlorophenylalanine results in suppression of serotonergic system and disturbance of swimming movements in newborn rats. Neurosci Res. 1998, 31: 155-169. 10.1016\/S0168-0102(98)00034-0.","journal-title":"Neurosci Res"},{"key":"65_CR18","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S1095-6433(99)00160-9","volume":"125","author":"GT Shishkina","year":"2000","unstructured":"Shishkina GT, Dygalo NN: Role of the serotoninergic system in the acceleration of sexual maturation in wild Norway rats selected for reduced aggressiveness toward humans. Comp Biochem Physiol C Toxicol Pharmacol. 2000, 125: 45-51.","journal-title":"Comp Biochem Physiol C Toxicol Pharmacol"},{"key":"65_CR19","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1186\/1477-7827-1-96","volume":"1","author":"IP Butkevich","year":"2003","unstructured":"Butkevich IP, Khozhai LI, Mikhailenko VA, Otellin VA: Decreased serotonin level during pregnancy alters morphological and functional characteristics of tonic nociceptive system in juvenile offspring of the rat. Reprod Biol Endocrinol. 2003, 1: 96-10.1186\/1477-7827-1-96.","journal-title":"Reprod Biol Endocrinol"},{"key":"65_CR20","first-page":"405","volume-title":"Psychoneuroimmunology","author":"GJM Maestroni","year":"1981","unstructured":"Maestroni GJM, Pierpaoli W: Pharmacologic control of the hormonall mediated immune response. Psychoneuroimmunology. Edited by: Ader R. 1981, Academic Press, New York, 405-425."},{"key":"65_CR21","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511546341","volume-title":"Seasonal patterns of stress, immune function and disease","author":"RJ Nelson","year":"2002","unstructured":"Nelson RJ, Demas GE, Klein SL, Kriegsfeld LJ: Seasonal patterns of stress, immune function and disease. 2002, Cambridge Univ Press. New York"},{"key":"65_CR22","first-page":"57","volume":"1","author":"DX Tan","year":"1993","unstructured":"Tan DX, Chen LD, Poeggeler B, Manchester LC, Reiter RJ: Melatonin a potent endogenous hydroxyl radical scavenger. Endocrinol J. 1993, 1: 57-61. 23","journal-title":"Endocrinol J"},{"key":"65_CR23","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1111\/j.1749-6632.2000.tb05402.x","volume":"917","author":"RJ Reiter","year":"2000","unstructured":"Reiter RJ, Calvo JR, Karbownik M, Qi W, Tan DX: Melatonin and its relation to immune system and inflammation. Ann N Y Acad Sci. 2000, 917: 376-386.","journal-title":"Ann N Y Acad Sci"},{"key":"65_CR24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1046\/j.1600-079X.2003.00092.x","volume":"36","author":"C Rodriguez","year":"2004","unstructured":"Rodriguez C, Mayo JC, Sainz RM, Antolin I, Herrera F, Martin V, Reiter RJ: Regulation of antioxidant enzymes: a significant role for melatonin. J Pineal Res. 2004, 36: 1-9. 10.1046\/j.1600-079X.2003.00092.x.","journal-title":"J Pineal Res"},{"key":"65_CR25","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1159\/000046899","volume":"10","author":"KS Bishnupuri","year":"2001","unstructured":"Bishnupuri KS, Haldar C: Maternal Transfer of melatonin alters the growth and sexual maturation of young Indian palm squirrel, F. pennanti. Biological Signal and Receptors. 2001, 10: 317-325.","journal-title":"Biological Signal and Receptors"},{"key":"65_CR26","doi-asserted-by":"crossref","first-page":"115","DOI":"10.4049\/jimmunol.112.1.115","volume":"112","author":"P Phanuphak","year":"1974","unstructured":"Phanuphak P, Moorhead JW, Claman NH: Tolerance and contact sensitivity to DNFD in mice. I. In vivo detection by ear swelling and correlation with in vitro b cell stimulation. J Immunol. 1974, 112: 115-123.","journal-title":"J Immunol"},{"key":"65_CR27","first-page":"1347","volume":"6","author":"ML Disis","year":"2000","unstructured":"Disis ML, Schiffman K, Gooley T, McNeel D, Rinn K, Knutson KL: Delayed-Type Hypersensitivity Response Is a Predictor of Peripheral Blood T-Cell Immunity after HER-2\/neu Peptide Immunization. Clinical Cancer Research. 2000, 6: 1347-1350.","journal-title":"Clinical Cancer Research"},{"key":"65_CR28","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1016\/S0022-2275(20)40690-X","volume":"19","author":"H Ohkawa","year":"1978","unstructured":"Ohkawa H, Ohishi N, Yagi K: Reaction of linoleic acid hydroperoxide with thiobarbuteric acid. Journal of Lipid Research. 1978, 19: 1053-1057.","journal-title":"Journal of Lipid Research"},{"key":"65_CR29","doi-asserted-by":"publisher","first-page":"40","DOI":"10.3181\/00379727-140-36391","volume":"140","author":"JL Pauly","year":"1972","unstructured":"Pauly JL, Sokal JE: A simplified technique for in vitro studies of lymphocytes reactivity. Proc Soc Exp Biol Med. 1972, 140: 40-44.","journal-title":"Proc Soc Exp Biol Med"},{"key":"65_CR30","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1210\/endo-98-2-482","volume":"98","author":"MD Rollag","year":"1976","unstructured":"Rollag MD, Niswender GD: Radioimmunoassay of melatonin in sheep exposed to different light regimes. Endocrinol. 1976, 98: 482-488.","journal-title":"Endocrinol"},{"key":"65_CR31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/09291010500224215","volume":"37","author":"Chandana Haldar","year":"2006","unstructured":"Haldar Chandana, Sharma Shalini, Singh Shiv: Reproductive phase dependent circadian variations of plasma melatonin, testosterone, thyroxine and corticosterone in Indian palm squirrel, Funambulus pennanti. Biol Rhythm Res. 2006, 37: 1-10. 10.1080\/09291010500224215.","journal-title":"Biol Rhythm Res"},{"key":"65_CR32","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1111\/j.1749-6632.1991.tb16987.x","volume":"621","author":"W Pierpaoli","year":"1991","unstructured":"Pierpaoli W, Dall'ara A, Pedrinis E, Regelson W: The Pineal control of aging: the effects of melatonin and pineal grafting on the survival of older mice. Ann New Yark Acad Sci. 1991, 621: 291-313. 10.1111\/j.1749-6632.1991.tb16987.x.","journal-title":"Ann New Yark Acad Sci"},{"key":"65_CR33","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1073\/pnas.91.2.787","volume":"91","author":"W Pierpaoli","year":"1994","unstructured":"Pierpaoli W, Regelson W: Pineal control of aging: effect of melatonin and pineal grafting on aging mice. Proc Natl Acad Sci. 1994, 91: 787-791. 10.1073\/pnas.91.2.787.","journal-title":"Proc Natl Acad Sci"},{"key":"65_CR34","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1016\/S0531-5565(01)00120-6","volume":"36","author":"Y Touitou","year":"2001","unstructured":"Touitou Y: Human aging and melatonin. Clinical relevance. Experimental Gerontology. 2001, 36: 1083-1100. 10.1016\/S0531-5565(01)00120-6.","journal-title":"Experimental Gerontology"},{"key":"65_CR35","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/0165-5728(86)90047-0","volume":"13","author":"GJM Maestroni","year":"1986","unstructured":"Maestroni GJM, Conti A, Pierpaoli W: Role of pineal gland in immunity: Circadian synthesis and release of melatonin modulates the antibody response and antagonizes the immune suppressive effect of corticosterone. J Neuroimmunol. 1986, 13: 19-30. 10.1016\/0165-5728(86)90047-0.","journal-title":"J Neuroimmunol"},{"issue":"1","key":"65_CR36","first-page":"59","volume":"9","author":"C Csaba","year":"1975","unstructured":"Csaba C, Sudar F, Dobozy O: Morphological changes of thymus and the thyroid gland after extirpation of pineal body. Endocrinol Exp. 1975, 9 (1): 59-67.","journal-title":"Endocrinol Exp."},{"issue":"3","key":"65_CR37","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1111\/j.1742-7843.2005.pto_973141.x","volume":"97","author":"R Juan","year":"2005","unstructured":"Juan R, Mu\u00f1oz-Casta\u00f1eda , Montilla Pedro, Mu\u00f1oz Maria, Bujalance Immaculada, Muntan\u00e9 Jordi, T\u00fanez Isaac: Parachlorophenylalanine Exacerbates Oxidative Stress Induced by Gentamicin in Rats. Basic Clin Pharmacol Toxicol. 2005, 97 (3): 174-178. 10.1111\/j.1742-7843.2005.pto_973141.x.","journal-title":"Basic Clin Pharmacol Toxicol."},{"issue":"7-8","key":"65_CR38","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1016\/S0891-5849(99)00131-8","volume":"27","author":"Y Urata","year":"1999","unstructured":"Urata Y, Honma S, Goto S, Todoroki S, Iida T, Cho S, Honma K, Kondo T: Melatonin induces gamaglutamylcysteine synthetase mediated by activator protein-1 in human vascular endothelial cells. Free Radic Biol Med. 1999, 27 (7-8): 838-847. 10.1016\/S0891-5849(99)00131-8.","journal-title":"Free Radic Biol Med."},{"key":"65_CR39","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1080\/09553000600774105","volume":"82","author":"S Sharma","year":"2006","unstructured":"Sharma S, Haldar C: Melatonin prevents x-ray induced oxidative damages in peripheral blood and spleen of seasonally breeding rodent, during reproductively active phase. Int J Rad Biol. 2006, 82: 411-419. 10.1080\/09553000600774105.","journal-title":"Int J Rad Biol"}],"container-title":["Immunity &amp; Ageing"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1742-4933-6-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T22:37:02Z","timestamp":1684967822000},"score":1,"resource":{"primary":{"URL":"https:\/\/immunityageing.biomedcentral.com\/articles\/10.1186\/1742-4933-6-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,4,23]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2009,12]]}},"alternative-id":["65"],"URL":"https:\/\/doi.org\/10.1186\/1742-4933-6-5","relation":{},"ISSN":["1742-4933"],"issn-type":[{"value":"1742-4933","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,4,23]]},"assertion":[{"value":"23 December 2008","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 April 2009","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 April 2009","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"5"}}