Introduction: Recent data indicate that there is a link between depression and diabetes and that excess glucocorticoids may play an underlying role in the pathogenesis of both of these diseases. The aim of the present study was to determine whether there are any alterations in glucose, glycogen, glucose transporters, insulin, insulin receptors or corticosterone concentrations in the hippocampus and frontal cortex in a prenatal stress rat model of depression. Methods: Male rats whose mothers had been subjected to stress and control animals were subjected to the Porsolt test to verify the experimental model. Next, some of the rats were subjected to acute stress and/or were administered glucose. Glucose, glycogen, corticosterone, insulin, insulin receptor, phospho-insulin receptor and glucose transporter (GLUT1, GLUT3 and GLUT4) concentrations were assayed. Results: Prenatally stressed rats exhibited glucose and glycogen concentrations in both investigated brain structures that exceeded those of the control animals. Prenatal stress also increased the levels of glucose transporters - GLUT1 in both tissues and GLUT4 in the frontal cortex. The changes in the prenatally stressed rats were more prominent in the animals that were subjected to stress or glucose loading in adulthood. Conclusion: The increase in carbohydrate brain concentrations evoked by prenatal stress may result from changes in the amounts of glucose transporters, especially GLUT1. Moreover, the obtained results support the hypothesis that stress during the perinatal period permanently increases the sensitivity of brain tissue to factors that act in adulthood.

Massart R, Mongeau R, Lanfumey L: Beyond the monoaminergic hypothesis: neuroplasticity and epigenetic changes in a transgenic mouse model of depression. Philos Trans R Soc Lond B Biol Sci 2012;367:2485-2494.
Zunszain PA, Anacker C, Cattaneo A, Carvalho LA, Pariante CM: Glucocorticoids, cytokines and brain abnormalities in depression. Prog Neuropsychopharmacol Biol Psychiatry 2011;35:722-729.
Duman RS: Pathophysiology of depression: the concept of synaptic plasticity. Eur Psychiatry 2002;17(suppl 3):306-310.
Marsden WN: Synaptic plasticity in depression: molecular, cellular and functional correlates. Prog Neuropsychopharmacol Biol Psychiatry 2013;43:168-184.
Sterner EY, Kalynchuk LE: Behavioral and neurobiological consequences of prolonged glucocorticoid exposure in rats: relevance to depression. Prog Neuropsychopharmacol Biol Psychiatry 2010;34:777-790.
Magariños AM, McEwen BS: Stress-induced atrophy of apical dendrites of hippocampal CA3c neurons: involvement of glucocorticoid secretion and excitatory amino acid receptors. Neuroscience 1995;69:89-98.
Sousa N, Lukoyanov NV, Madeira MD, Almeida OF, Paula-Barbosa MM: Reorganization of the morphology of hippocampal neuritis and synapses after stress-induced damage correlates with behavioral improvement. Neuroscience 2000;97:253-266.
Lemaire V, Koehl M, Le Moal M, Abrous DN: Prenatal stress produces learning deficits associated with an inhibition of neurogenesis in the hippocampus. Proc Natl Acad Sci U S A 2000;97:11032-11037.
Sapolsky RM: Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch Gen Psychiatry 2000;57:925-935.
Duman RS, Warner-Schmidt JL: Hippocampal neurogenesis: opposing effects of stress and antidepressant treatment. Hippocampus 2006;16:239-249.
Wellman CL: Dendritic reorganization in pyramidal neurons in medial prefrontal cortex after chronic corticosterone administration. J Neurobiol 2001;49:245-253.
Leonard BE, Myint A: The psychoneuroimmunology of depression. Hum Psychopharmacol 2009;24:165-175.
Pariante CM, Lightman SL: The HPA axis in major depression: classical theories and new developments. Trends Neurosci 2008;31:464-468.
Myers B, McKlveen JM, Herman JP: Glucocorticoid actions on synapses, circuits, and behavior: implications for the energetics of stress. Front Neuroendocrinol 2014;35:180-196.
Wyrwoll CS, Holmes MC: Prenatal excess glucocorticoid exposure and adult affective disorders: a role for serotonergic and catecholamine pathways. Neuroendocrinology 2012;95:47-55.
Tata DA, Anderson BJ: The effects of chronic glucocorticoid exposure on dendritic length, synapse numbers and glial volume in animal models: implications for hippocampal volume reductions in depression. Physiol Behav 2010;99:186-193.
Li L, Li X, Zhou W, Messina JL: Acute psychological stress results in the rapid development of insulin resistance. J Endocrinol 2013;217:175−184.
Detka J, Kurek A, Basta-Kaim A, Kubera M, Lasoń W, Budziszewska B: Neuroendocrine link between stress, depression and diabetes. Pharmacol Rep 2013;65:1591-1600.
Magariños AM, McEwen BS: Experimental diabetes in rats causes hippocampal dendritic and synaptic reorganization and increased glucocorticoid reactivity to stress. Proc Natl Acad Sci U S A 2000;97:11056−11061.
McEwen BS, Magariños AM, Reagan LP: Studies of hormone action in the hippocampal formation: possible relevance to depression and diabetes. J Psychosom Res 2002;53:883−890.
Grillo CA, Piroli GG, Kaigler KF, Wilson SP, Wilson MA, Reagan LP: Downregulation of hypothalamic insulin receptor expression elicits depressive-like behaviors in rats. Behav Brain Res 2011;222:230−235.
Hryhorczuk C, Sharma S, Fulton SE: Metabolic disturbances connecting obesity and depression. Front Neurosci 2013;7:177.
Pan Y, Hong Y, Zhang QY, Kong LD: Impaired hypothalamic insulin signaling in CUMS rats: restored by icariin and fluoxetine through inhibiting CRF system. Psychoneuroendocrinology 2013;38:122-134.
Choeiri C, Staines W, Messier C: Immunohistochemical localization and quantification of glucose transporters in the mouse brain. Neuroscience 2002;111:19-34.
Szymańska M, Budziszewska B, Jaworska-Feil L, Basta-Kaim A, Kubera M, Leśkiewicz M, Regulska M, Lasoń W: The effect of antidepressant drugs on the HPA axis activity, glucocorticoid receptor level and FKBP51 concentration in prenatally stressed rats. Psychoneuroendocrinology 2009;34:822-832.
Nyirenda MJ, Seckl JR: Intrauterine events and the programming of adulthood disease: the role of fetal glucocorticoid exposure (review). Int J Mol Med 1998;2:607-614.
Nyirenda MJ, Welberg LAM, Seckl JR: Programming hyperglycaemia in the rat through prenatal exposure to glucocorticoids-fetal effect or maternal influence? J Endocrinology 2001;170:653−660.
Morley-Fletcher S, Darnaudery M, Koehl M, Casolini P, Van Reeth O, Maccari S: Prenatal stress in rats predicts immobility behavior in the forced swim test. Effects of a chronic treatment with tianeptine. Brain Res 2003;989:246-251.
Morley-Fletcher S, Darnaudery M, Mocaer E, Froger N, Lanfumey L, Laviola G, Casolini P, Zuena AR, Marzano L, Hamon M, Maccari S: Chronic treatment with imipramine reverses immobility behaviour, hippocampal corticosteroid receptors and cortical 5-HT(1A) receptor mRNA in prenatally stressed rats. Neuropharmacology 2004;47:841-847.
Porsolt RD, Anton G, Blavet N, Jalfre M: Behavioural despair in rats: a new model sensitive to antidepressant treatments. Eur J Pharmacol 1978;47:379-391.
Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265-275.
Budziszewska B, Szymańska M, Leskiewicz M, Basta-Kaim A, Jaworska-Feil L, Kubera M, Jantas D, Lason W: The decrease in JNK- and p38-MAP kinase activity is accompanied by the enhancement of PP2A phosphate level in the brain of prenatally stressed rats. J Physiol Pharmacol 2010;61:207-215.
Rao U, McGinty DJ, Shinde A, McCracken JT, Poland RE: Prenatal stress is associated with depression-related electroencephalographic sleep changes in adult male rats: a preliminary report. Prog Neuropsychopharmacol Biol Psychiatry 1999;23:929-939.
Szymańska M, Suska A, Budziszewska B, Jaworska-Feil L, Basta-Kaim A, Leśkiewicz M, Kubera M, Gergont A, Kroczka S, Kaciński M, Lasoń W: Prenatal stress decreases glycogen synthase kinase-3 phosphorylation in the rat frontal cortex. Pharmacol Rep 2009;61:612-620.
Kreider ML, Tate CA, Cousins MM, Oliver CA, Seidler FJ, Slotkin TA: Lasting effects of developmental dexamethasone treatment on neural cell number and size, synaptic activity, and cell signaling: critical periods of vulnerability, dose-effect relationships, regional targets, and sex selectivity. Neuropsychopharmacology 2006;31:12-35.
Murgatroyd C, Patchev AV, Wu Y, Micale V, Bockmühl Y, Fischer D, Holsboer F, Wotjak CT, Almeida OF, Spengler D: Dynamic DNA methylation programs persistent adverse effects of early-life stress. Nat Neurosci 2009;12:1559-1566.
Sickmann HM, Walls AB, Schousboe A, Bouman SD, Waagepetersen HS: Functional significance of brain glycogen in sustaining glutamatergic neurotransmission. J Neurochem 2009;109(suppl 1):80-86.
Yu S, Ding WG: The 45 kDa form of glucose transporter 1 (GLUT1) is localized in oligodendrocyte and astrocyte but not in microglia in the rat brain. Brain Res 1998;797:65-72.
Langdown ML, Holness MJ, Sugden MC: Early growth retardation induced by excessive exposure to glucocorticoids in utero selectively increases cardiac GLUT1 protein expression and Akt/protein kinase B activity in adulthood. J Endocrinol 2001;169:11-22.
Levitt NS, Lindsay RS, Holmes MC, Seckl JR: Dexamethasone in the last week of pregnancy attenuates hippocampal glucocorticoid receptor gene expression and elevates blood pressure in the adult offspring in the rat. Neuroendocrinology 1996;64:412-418.
Tarry-Adkins JL, Ozanne SE: Mechanisms of early life programming: current knowledge and future directions. Am J Clin Nutr 2011;94(6 suppl):1765S-1771S.
Gerhart DZ, Leino RL, Taylor WE, Borson ND, Drewes LR: GLUT1 and GLUT3 gene expression in gerbil brain following brief ischemia: an in situ hybridization study. Brain Res Mol Brain Res 1994;25:313-322.
Carver FM, Shibley IA Jr, Miles DS, Pennington JS, Pennington SN: Increased intracellular localization of brain GLUT-1 transporter in response to ethanol during chick embryogenesis. Am J Physiol 1999;277:E750-E759.
Grillo CA, Piroli GG, Hendry RM, Reagan LP: Insulin-stimulated translocation of GLUT4 to the plasma membrane in rat hippocampus is PI3-kinase dependent. Brain Res 2009;1296:35-45.
Vogt MC, Brüning JC: CNS insulin signaling in the control of energy homeostasis and glucose metabolism - from embryo to old age. Trends Endocrinol Metab 2013;24:76−84.
Pratchayasakul W, Kerdphoo S, Petsophonsakul P, Pongchaidecha A, Chattipakorn N, Chattipakorn SC: Effects of high-fat diet on insulin receptor function in rat hippocampus and the level of neuronal corticosterone. Life Sci 2011;88:619−627.
Suenaga T, Yukie M, Gao S, Nakahara D: Sex-specific effects of prenatal stress on neuronal development in the medial prefrontal cortex and the hippocampus. Neuroreport 2012;23:430-435.
Yeh CM, Huang CC, Hsu KS: Prenatal stress alters hippocampal synaptic plasticity in young rat offspring through preventing the proteolytic conversion of pro-brain-derived neurotrophic factor (BDNF) to mature BDNF. J Physiol 2012;590:991-1010.
Van den Hove DL, Kenis G, Brass A, Opstelten R, Rutten BP, Bruschettini M, Blanco CE, Lesch KP, Steinbusch HW, Prickaerts J: Vulnerability versus resilience to prenatal stress in male and female rats; implications from gene expression profiles in the hippocampus and frontal cortex. Eur Neuropsychopharmacol 2013;23:1226-1246.
Chiu SL, Chen CM, Cline HT: Insulin receptor signaling regulates synapse number, dendritic plasticity, and circuit function in vivo. Neuron 2008;58:708−719.
Haj-ali V, Mohaddes G, Babri SH: Intracerebroventricular insulin improves spatial learning and memory in male Wistar rats. Behav Neurosci 2009;123:1309-1314.
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