The Effects of Stress during Pregnancy on Anxiety-like Behaviors, Spatial memory, Plasma and Hippocampal Leptin Levels, and Leptin Receptor Gene Expression in the Hippocampus of Small Mice
Subject Areas : Journal of Animal BiologyMasoomeh Mohammadi 1 , Ali Haeri Rohani 2 , هدایت صحرایی 3 , Parichehreh Yaghmaei 4
1 - Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
2 - Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
3 - Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
4 - Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Keywords: Pregnancy stress, Anxiety, Spatial memory, Leptin receptor,
Abstract :
One of the possible reasons for the decrease in cognitive abilities and spatial memory in offspring is the decrease in leptin receptor gene expression in the hippocampus. In the present study, pregnant NMRI rats were divieded into four groups of eight: 1- male control group: male offspring of mothers who did not receive electric shock during pregnancy 2- Female control group: female offspring of mothers who did not receive electric shock during pregnancy 3- Male stress group: female offspring of mothers who received electric shock during pregnancy, and 4- female stress group: female offspring of mothers who received electric shock during pregnancy. To evaluate the effect of stress on intrinsic anxiety, the open field device was used, and for induced anxiety, an elevated plus maze was used. Leptin plasma concentration and leptin receptor gene expression in the hippocampus were measured. The results showed that plantar electric shock stress in the first half of pregnancy can reduce leptin plasma levels in offspring. The incidence of anxiety-like behaviors in male and female offspring of mothers who received shocks increased significantly (p < 0.05 and p < 0.01). Also, the studies showed that male and female offspring of stressed mothers traveled more time and distance to reach the target chamber in the Barnes Maze (memory test). Prenatal stress will reduce the plasma concentration of leptin and hippocampal leptin in male and female offspring. Leptin receptor gene expression in the hippocampus of male and female offspring of stressed mothers was significantly lower than that of control group offspring. Exposure of pregnant mothers to electric shock led to a decrease in leptin hormone levels in offspring, which was associated with anxiety-like behaviors and impaired memory and spatial learning. Considering the existence of various types of environmental stress in today's life, leptin measurement and evaluation may play a decisive role in predicting the treatment of patients with anxiety and cognitive disorders.
.
1. Aliabadi N., Sahraei H., Bahari Z., Meftahi G. 2018. Effect of prenatal immobilization stress on spatial memory, anxiety-like behavior and brain BDNF concentration in the F1 generation male mice. Scientific Journal of Kurdistan University of Medical Sciences, 23(3):73-84.
2. Arnsten A.F. 2009. Stress signalling pathways that impair prefrontal cortex structure and function. Nature Reviews. Neuroscencei, 10(6):410-422.
3. Bouret S.G. 2010. Neurodevelopmental actions of leptin. Brain Research, 1350:2-9.
4. Champagne D.L., Bagot R.C., van Hasselt F., Ramakers G., Meaney M.J., de Kloet E.R., Joëls M, Krugers H. 2008. Maternal care and hippocampal plasticity: evidence for experience-dependent structural plasticity, altered synaptic functioning, and differential responsiveness to glucocorticoids and stress. Journal of Neuroscience, 28(23):6037-6045.
5. Ehlers C.L., Koob G.F. 1985. Locomotor behavior following kindling in three different brain sites. Brain Research, 326(1):71-79.
6. Garza J.C., Guo M., Zhang W., Lu X.Y. 2012. Leptin restores adult hippocampal neurogenesis in a chronic unpredictable stress model of depression and reverses glucocorticoid-induced inhibition of GSK-3β/β-catenin signaling. Molecular Psychiatry, 17(8):790.808.
7. Glover V. 2015. Prenatal stress and its effects on the fetus and the child: possible underlying biological mechanisms. Advances in Neurobiology, 10:269-283.
8. Harvey J., Solovyova N., Irving A. 2006. Leptin and its role in hippocampal synaptic plasticity. Progress in Lipid Research, 45(5):369-378.
9. Huizink A.C., Mulder E.J., Buitelaar J.K. 2004. Prenatal stress and risk for psychopathology: specific effects or induction of general susceptibility?. Psychological Bulletin, 130(1):115-142.
10. Ishii S., Hashimoto-Torii K. 2015. Impact of prenatal environmental stress on cortical development. Frontiers in Cell Neuroscience, 9:207-217.
11. Ko M.C., Hung Y.H., Ho P.Y., Yang Y.L., Lu K.T. 2014. Neonatal glucocorticoid treatment increased depression-like behaviour in adult rats. International Journal of Neuropsychopharmacology, 17(12):1995-2004.
12. Maccari S., Morley-Fletcher S. 2007. Effects of prenatal restraint stress on the hypothalamus-pituitary-adrenal axis and related behavioural and neurobiological alterations. Psychoneuroendocrinology, 1:S10-5.
13. Mainardi M., Pizzorusso T., Maffei M. 2013. Environment, leptin sensitivity, and hypothalamic plasticity. Neural Plasticity, 2013:438072.
14. Marwarha G., Dasari B., Prasanthi J.R., Schommer J., Ghribi O. 2010. Leptin reduces the accumulation of Aβ and phosphorylated tau induced by 27-hydroxycholesterol in rabbit organotypic slices. Alzheimers Disease, 19(3):1007-1019.
15. Mercer J.G., Hoggard N., Williams L.M., Lawrence C.B., Hannah L.T., Trayhurn P. 1996. Localization of leptin receptor mRNA and the long form splice variant (Ob-Rb) in mouse hypothalamus and adjacent brain regions by in situ hybridization. FEBS Letters, 387(2-3):113-116.
16. Oitzl M.S., Champagne D.L., van der Veen R., de Kloet E.R. 2010. Brain development under stress: hypotheses of glucocorticoid actions revisited. Neuroscience and Behavioral Review, 34(6):853-866.
17. Oomura Y., Hori N., Shiraishi T., Fukunaga K., Takeda H., Tsuji M., Matsumiya T., Ishibashi M., Aou S., Li X.L., Kohno D., Uramura K., Sougawa H., Yada T., Wayner M.J., Sasaki K. 2006. Leptin facilitates learning and memory performance and enhances hippocampal CA1 long-term potentiation and CaMK II phosphorylation in rats. Peptides, 27(11):2738-2749.
18. Pothuizen H.H., Jongen-Rêlo A.L., Feldon J. 2005. The effects of temporary inactivation of the core and the shell subregions of the nucleus accumbens on prepulse inhibition of the acoustic startle reflex and activity in rats. Neuropsychopharmacology, 30(4):683-696.
19. Schmitt A., Malchow B., Hasan A., Falkai P. 2014. The impact of environmental factors in severe psychiatric disorders. Frontiers in Neuroscience, 8:19-27.
20. Seibenhener M.L., Wooten M.C. 2015. Use of the open field maze to measure locomotor and anxiety-like behavior in mice. Journal of Visualized Experiments, (96):e52434.
21. Teryaeva N.B. 2015. Leptin as a neuroprotector and a central nervous system functional stability factor. Neuroscience and Behavioral Physiology, 45(6):612-618.
22. Valentino R.J., Bangasser D., Van Bockstaele E.J. 2013. Sex-biased stress signaling: the corticotropin-releasing factor receptor as a model. Molecular Pharmacology, 83(4):737-745.
23. Walker A.G., Wenthur C.J., Xiang Z., Rook J.M., Emmitte K.A., Niswender C.M., Lindsley C.W., Conn P.J. 2015. Metabotropic glutamate receptor 3 activation is required for long-term depression in medial prefrontal cortex and fear extinction. Proceedings of the National Academy of Sciences of America, 112(4):1196-1201.
24. Wilson C.A., Terry A.V. 2013. Variable maternal stress in rats alters locomotor activity, social behavior, and recognition memory in the adult offspring. Pharmacology, Biochemistry and Behavior, 104:47-61.
25. Yaka R., Salomon S., Matzner H., Weinstock M. 2007. Effect of varied gestational stress on acquisition of spatial memory, hippocampal LTP and synaptic proteins in juvenile male rats. Behavioral Brain Research, 179(1):126-132.