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Adrenergic, dopaminergic and serotonergic gene expression in low dose, long time insulin and somatotropin treatment to ageing rats: rejuvenation of brain function

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Abstract

Somatotropin (GH) and insulin (INS) low dose, long-term brain rejuvenation effect was studied in the cerebral cortex using NE, EPI, DA and 5-HT receptor subtypes of young (group I—treatment started 4 weeks continued to 16 weeks) and old rats (group II—treatment started 60 weeks continued to 90 weeks). GH and INS treatment showed significant decrease in NE and EPI content in cerebral cortex of both young and old rats. α2A-adrenergic receptors showed decreased expression whereas β2-adrenergic receptors showed enhanced expression with age. GH and INS treatment significantly increased α2A-adrenergic receptor protein in group I rats whereas INS treatment could increase β2-adrenergic receptor protein expression in group II rats. DA and 5-HT content decrease with age. GH and INS administration showed increase in DA and 5-HT content in the brain regions-corpus striatum and brainstem of both young and old rats. Also, DA D2 and 5-HT2C receptor gene expression were increased significantly by GH and INS treatment in both young and old rats. In conclusion, low dose, long-term treatment of INS and GH to ageing rats improved the adrenergic, dopaminergic and serotonergic receptor subtypes activity and rejuvenation of brain function.

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References

  • Abraham A, Paulose CS (1999) Age-related alterations in noradrenergic function in the brainstem of streptozotocin-diabetic rats. J Biochem Mol Biol Biophys 3:171–176

    CAS  Google Scholar 

  • Ajo R, Cacicdeo L, Gonzsalex B, Sanchez-Franco F (2001) Growth Hormone stimulates proliferation and differentiation of embryonic brain cells via MAP/ERK signaling pathways. In: Abstracts of 83rd annual meeting of endocrine society, pp 1–28

  • Arianna R, Silvia M, Alberto O, Andrea M (2007) D1 and D2 receptor antagonist injections in the prefrontal cortex selectively impair spatial learning in mice. Neuropsychopharmacology 32:309–319

    Article  CAS  Google Scholar 

  • Bartke A (2006) Long-lived Klotho mice: new insights into the roles of IGF-1 and insulin in aging. Trends Endocrinol Metab 17:33–35

    Article  PubMed  CAS  Google Scholar 

  • Ben-Jonathan N, Hnasko R (2001) Dopamine as a prolactin (PRL) inhibitor. Endocr Rev 22:724–763

    Article  PubMed  CAS  Google Scholar 

  • Birnbaum S, Gobeske KT, Auerbach J, Taylor JR, Arnsten AF (1999) A role for norepinephrine in stress-induced cognitive deficits: alpha-1-adrenoceptor mediation in the prefrontal cortex. Biol Psychiatry 46:1266–1274

    Article  PubMed  CAS  Google Scholar 

  • Bücheler MM, Hadamek K, Hein L (2002) Two alpha(2)-adrenergic receptor subtypes, alpha(2A) and alpha(2C), inhibit transmitter release in the brain of gene-targeted mice. Neuroscience 109:819–826

    Article  PubMed  Google Scholar 

  • Burke MR, Barnes GR (2006) Quantitative differences in smooth pursuit and saccadic eye movements. Exp Brain Res 175:596–608

    Article  PubMed  CAS  Google Scholar 

  • Cristina C, Díaz-Torga G, Baldi A, Góngora A, Rubinstein M, Low MJ, Becú Villalobos D (2005) Increased pituitary vascular endothelial growth factor-a in dopaminergic D2 receptor knockout female mice. Endocrinology 146:2952–2962

    Article  PubMed  CAS  Google Scholar 

  • Díaz-Torga G, Feierstein C, Libertun C, Gelman D, Kelly MA, Low MJ, Rubinstein M, Becú-Villalobos D (2002) Disruption of the D2 dopamine receptor alters GH and IGF-I secretion and causes dwarfism in male mice. Endocrinology 143:1270–1279

    Article  PubMed  Google Scholar 

  • Eswar Shankar PN, Joseph A, Paulose CS (2007) Decreased [3H] YM-09151–2 binding to dopamine D2 receptors in the hypothalamus, brainstem and pancreatic islets of streptozotocin-induced diabetic rats. Eur J Pharmacol 557:99–105

    Article  CAS  Google Scholar 

  • Geinisman Y, de Toledo-Morrell L, Morrell F, Persina IS, Rossi M (1992) Age-related loss of axospinous synapses formed by two afferent systems in the rat dentate gyrus as revealed by the unbiased stereological dissector technique. Hippocampus 2:437–444

    Article  PubMed  CAS  Google Scholar 

  • Ghigo E, Bartolotta E, Imperiale E, Bellone J, Cardinale G, Aimaretti G, Valetto MR, Cherubini V, Maccario M, Cocchi D et al (1994) Glucagon stimulates GH secretion after intramuscular but not intravenous administration. Evidence against the assumption that glucagon per se has a GH-releasing activity. J Endocrinol Invest 17:849–854

    PubMed  CAS  Google Scholar 

  • Giustina A, Veldhuis JD (1998) Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human. Endocr Rev 19:717–797. doi:10.1210/er.19.6.717

    Article  PubMed  CAS  Google Scholar 

  • Glowinski J, Iversen LL (1966) Regional studies of catecholamines in the rat brain: the disposition of [3H] Norepinephrine, [3H] DOPA in various regions of the brain. J Neurochem 13:655–669. doi:10.1111/j.1471-4159.1966.tb09873.x

    Article  PubMed  CAS  Google Scholar 

  • Guillod-Maximin E, Lorsignol A, Alquier T, Penicaud L (2004) Acute intracarotid glucose injection towards the brain induces specific c-fos activation in hypothalamic nuclei: involvement of astrocytes in cerebral glucose-sensing in rats. J Neuroendocrinol 16:464–471

    Article  PubMed  CAS  Google Scholar 

  • Hafen E (2004) Cancer, type 2 diabetes, and ageing: news from flies and worms. Swiss Med Wkly 134:711–719

    PubMed  CAS  Google Scholar 

  • Harvey S, Lavelin I, Pines M (2002) Growth hormone (GH) action in the brain: neural expression of a GH-response gene. J Mol Neurosci 18:89–95. doi:10.1385/JMN:18:1-2:89

    Article  PubMed  CAS  Google Scholar 

  • Jaffe CA, Barkan AL (1992) Treatment of acromegaly with dopamine agonists. Endocrinol Metab Clin North Am 21:713–735

    PubMed  CAS  Google Scholar 

  • Jaffe CA, DeMott-Friberg R, Barkan AL (1996) Endogenous growth hormone (GH)-releasing hormone is required for GH responses to pharmacological stimuli. J Clin Invest 97:934–940. doi:10.1172/JCI118516

    Article  PubMed  CAS  Google Scholar 

  • Martin JB (1973) Functions of the hypothalamus and amygdala in regulation of growth hormone secretion. Trans Am Neurol Assoc 98:229–232

    PubMed  CAS  Google Scholar 

  • Minamitani N, Chihara K, Kaji H, Kodama H, Kita T, Fujita T (1989) Alpha 2 adrenergic control of growth hormone (GH) secretion in conscious male rabbits: involvement of endogenous GH-releasing factor and somatostatin. Endocrinology 125:2839–2845

    Article  PubMed  CAS  Google Scholar 

  • Mizoguchi H, Narita M, Wu H, Narita M, Suzuki T, Nagase H, Tseng LF (2000) Differential involvement of mu (1)-opioid receptors in endomorphin- and beta-endorphin-induced G-protein activation in the mouse pons/medulla. Neuroscience 100:835–839

    Article  PubMed  CAS  Google Scholar 

  • Morrione A, Valentinis B, Shi-qiong X, Yumet G, Louvi A, Efstratiadis A, Baserga R (1997) Insulin-like growth factor II stimulates cell proliferation through the insulin receptor. Proc Natl Acad Sci USA 94:3777–3782. doi:10.1073/pnas.94.8.3777

    Article  PubMed  CAS  Google Scholar 

  • Müller EE (1987) Neural control of somatotropic function. Physiol Rev 67:962–1053

    PubMed  Google Scholar 

  • Mustafa A, Sharma HS, Olsson Y, Gordh T, Thóren P, Sjöquist PO, Roos P, Adem A, Nyberg F (1995) Vascular permeability to growth hormone in the rat central nervous system after focal spinal cord injury. Influence of a new anti oxidant H 290/51 and age. Neurosci Res 23:185–194. doi:10.1016/0168-0102(95)00937-O

    Article  PubMed  CAS  Google Scholar 

  • Nicholson DA, Yoshida R, Berry RW, Gallagher M, Geinisman Y (2004) Reduction in size of perforated postsynaptic densities in hippocampal axospinous synapses and age-related spatial learning impairments. J Neurosci 24:7648–7653

    Article  PubMed  CAS  Google Scholar 

  • Nonogaki K (2000) New insights into sympathetic regulation of glucose and fat metabolism. Diabetologia 43:533–549

    Article  PubMed  CAS  Google Scholar 

  • Noriyuki K, Masakatsu K, Tadao K, Mitsuo S (1989) Electrical stimulation of specific brainstem nuclei suppresses growth hormone-releasing hormone-induced growth hormone secretion in the pentobarbital anaesthetized rat. J Neuroendocrinol 1:209–214

    Article  Google Scholar 

  • Padayatti PS, Paulose CS (1999) Alpha2 adrenergic and high affinity serotonergic receptor changes in the brain stem of streptozotocin-induced diabetic rats. Life Sci 65:403–414

    Article  PubMed  CAS  Google Scholar 

  • Papageorgiou A, Denef C (2007) Stimulation of growth hormone release by 5-hydroxytryptamine (5-HT) in cultured rat anterior pituitary cell aggregates: evidence for mediation by 5-HT2B, 5-HT7, 5-HT1B, and ketanserin-sensitive receptors. Endocrinology 148:4509–4522

    Article  PubMed  CAS  Google Scholar 

  • Paulose CS, Dakshinamurti K, Packer S, Stephens NL (1988) Sympathetic stimulation and hypertension in pyridoxine deficient adult rat. Hypertension 11:387–391

    PubMed  CAS  Google Scholar 

  • Phelps CJ, Romero MI, Hurley DL (2003) Growth hormone-releasing hormone-producing and dopaminergic neurones in the mouse arcuate nucleus are independently regulated populations. J Neuroendocrinol 15:280–288

    Article  PubMed  CAS  Google Scholar 

  • Plantjé JF, Schipper J, Verheijden PF, Stoof JC (1987) D2-dopamine receptors regulate the release of [3H] dopamine in rat basal hypothalamus and neurointermediate lobe of the pituitary gland. Brain Res 413:205–212

    Article  PubMed  Google Scholar 

  • Salvador GA, Ilincheta de Boschero MG, Pasquaré SJ, Giusto NM (2005) Phosphatidic acid and diacylglycerol generation is regulated by insulin in cerebral cortex synaptosomes from adult and aged rats. J Neurosci Res 81:244–252. doi:10.1002/jnr.20565

    Article  PubMed  CAS  Google Scholar 

  • Scheepens A, Sirimanne E, Beilharz E, Breier BH, Waters MJ, Gluckman PD, Williams CE (1999) Alterations in the neural growth hormone axis following hypoxic-ischemic brain injury. Brain Res Mol Brain Res 68:88–100

    Article  PubMed  CAS  Google Scholar 

  • Scheepens A, Sirimanne ES, Breier BH, Clark RG, Gluckman PD, Williams CE (2001) Growth hormone as a neuronal rescue factor during recovery from CNS injury. Neuroscience 104:677–687

    Article  PubMed  CAS  Google Scholar 

  • Tarazi FI, Zhang K, Baldessarini RJ (2001) Long-term effects of olanzapine, risperidone, and quetiapine on dopamine receptor types in regions of rat brain: implications for antipsychotic drug treatment. J Pharmacol Exp Ther 297:711–717

    PubMed  CAS  Google Scholar 

  • Tepper JM, Sun BC, Martin LP, Creese I (1997) Functional roles of dopamine D2 and D3 autoreceptors on nigrostriatal neurons analyzed by antisense knockdown in vivo. J Neurosci 17:2519–2530

    PubMed  CAS  Google Scholar 

  • Valverde Ignacio, Peñalva Angela, Dieguez Carlos (2000) Influence of different serotonin receptor subtypes on growth hormone secretion. Neuroendocrinology 71:145–153

    Article  PubMed  CAS  Google Scholar 

  • Zhao WQ, Chen H, Quon MJ, Alkon DL (2004) Insulin and the insulin receptor in experimental models of learning and memory. Eur J Pharmacol 490:71–81. doi:10.1016/j.ejphar.2004.02.045

    Article  PubMed  CAS  Google Scholar 

  • Zoli M, Agnati LF, Tinner B, Steinbusch HW, Fuxe K (1993) Distribution of dopamine-immunoreactive neurons and their relationships to transmitter and hypothalamic hormone-immunoreactive neuronal systems in the rat mediobasal hypothalamus. A morphometric and microdensitometric analysis. J Chem Neuroanat 6:293–310

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

Supported by grants from DST, DBT, ICMR, Govt. of India, and KSCSTE, Govt. of Kerala to Dr. C. S. Paulose. B. Savitha thanks Cochin University of Science and Technology for SRF.

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  1. Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin, Kerala, 682 022, India

    C. S. Paulose & Savitha Balakrishnan

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  1. C. S. Paulose
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  2. Savitha Balakrishnan
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Correspondence to C. S. Paulose.

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Paulose, C.S., Balakrishnan, S. Adrenergic, dopaminergic and serotonergic gene expression in low dose, long time insulin and somatotropin treatment to ageing rats: rejuvenation of brain function. Biogerontology 9, 429–439 (2008). https://doi.org/10.1007/s10522-008-9183-1

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  • DOI: https://doi.org/10.1007/s10522-008-9183-1

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