Prenatal stress increased γ2 GABAA receptor subunit gene expression in hippocampus and potentiated pentylenetetrazol-induced seizure in rats

Document Type : Original Article

Authors

1 Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran

2 Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran

3 Department of Physiology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran

4 Neurophysiology Research Center, Urmia University of Medical Sciences, Urmia, Iran

5 Department of Biostatistics , School of Medicine, Urmia University of Medical Sciences, Urmia, Iran

Abstract

Objective(s): Stress during pregnancy is able to bring extensive effects on neurobehavioral development in offspring. The GABAergic system plays a pivotal role in neuronal excitability, which can be affected by prenatal stress (PS). This study aimed to evaluate impact of the PS on γ2 subunit of gamma-aminobutyric acid A (GABAA) receptor gene expression in the hippocampus and seizure induced by pentylenetetrazol (PTZ) in developing rats.
Materials and Methods: In this experimental study, female Wistar rats were exposed to restraint stress during gestation and their offspring were studied on postnatal days 14 and 21 (P14 and P21, respectively) for epileptic behaviors and γ2 GABAA receptor subunit gene expression. Quantitative real-time PCR was used for evaluating the γ2 GABAA receptor subunit gene expression in rat pups. Meanwhile, PTZ was injected into the pups, and seizure behaviors were recorded for 60 min.
Results: The results showed that γ2 subunit mRNA expression significantly increased in the hippocampus of the stressed pups. The expression level of γ2 subunit was higher on P21 compared to that on P14 in both groups. Number of seizures with tonic–clonic features increased in pups of stressed group compared to the control group. Prenatal stress significantly caused an increase in the total score of seizure on P21.
Conclusion: The effect of PS on seizure susceptibility is age-specific; the increased γ2 subunit level in the hippocampus might be, at least in part, the underlying mechanism for PS-induced augmentation of seizures in immature rats.

Keywords

References

1. Vestergaard M, Wisborg K, Henriksen TB, Secher NJ, Ostergaard JR, Olsen J. Prenatal exposure to cigarettes, alcohol, and coffee and the risk for febrile seizures. Pediatrics 2005; 116:1089-1094.
2. Saboory E, Ebrahimi L, Roshan-Milani S, Hashemi P. Interaction of prenatal stress and morphine alters prolactin and seizure in rat pups. Physiol Behav 2015; 149:181-186.
3. Hashemi P, Roshan-Milani S, Saboory E, Ebrahimi L, Soltanineghad M. Interactive effects of prenatal exposure to restraint stress and alcohol on pentylenetetrazol-induced seizure behaviors in rat offspring. Alcohol 2016; 56:51-57.
4. Edwards HE, Dortok D, Tam J, Won D, Burnham WM. Prenatal stress alters seizure thresholds and the development of kindled seizures in infant and adult rats. Horm Behav 2002; 42:437-447.
5. Nejatbakhsh M, Saboory E, Bagheri M. Effect of prenatal stress on a5 GABAA receptor subunit gene expression in hippocampus and pilocarpine induced seizure in rats. Int J Dev Neurosci 2018; 68:66-71.
6. Maguire J, Salpekar JA. Stress, seizures, and hypothalamic–pituitary–adrenal axis targets for the treatment of epilepsy. Epilepsy Behav 2013; 26:352-362.
7. Joëls M. Stress, the hippocampus, and epilepsy. Epilepsia 2009; 50:586-597.
8. Elliott EM, Sapolsky RM. Corticosterone enhances kainic acid‐induced calcium elevation in cultured hippocampal neurons. J Neurochem 1992; 59:1033-1040.
9. Olsen RW, Sieghart W. GABA A receptors: subtypes provide diversity of function and pharmacology. Neuropharmacology 2009; 56:141-148.
10. Ling I, Mihalik B, Etherington L-A, Kapus G, Pálvölgyi A, Gigler G, et al. A novel GABA A alpha 5 receptor inhibitor with therapeutic potential. Eur J Pharmacol 2015; 764:497-507.
11. Sieghart W. Structure, pharmacology, and function of GABA A receptor subtypes. Adv Pharmacol 2006; 54:231-263.
12. Brockhaus J, Pape H-C. Abnormalities in GABAergic synaptic transmission of intralaminar thalamic neurons in a genetic rat model of absence epilepsy. Mol Cell Neurosci 2011; 46:444-451.
13. Hines RM, Davies PA, Moss SJ, Maguire J. Functional regulation of GABA A receptors in nervous system pathologies. Curr Opin Neurobiol 2012; 22:552-558.
14. Hirose S. Mutant GABA (A) receptor subunits in genetic (idiopathic) epilepsy. Prog Brain Res 2014; 213:55-85.
15. Schwarzer C, Tsunashima K, Wanzenböck C, Fuchs K, Sieghart W, Sperk G. GABAA receptor subunits in the rat hippocampus II: altered distribution in kainic acid-induced temporal lobe epilepsy. Neuroscience 1997; 80:1001-1017.
16. Gunn BG, Cunningham L, Mitchell SG, Swinny JD, Lambert JJ, Belelli D. GABAA receptor-acting neurosteroids: a role in the development and regulation of the stress response. Front Neuroendocrinol 2015; 36:28-48.
17. Skilbeck KJ, Johnston GA, Hinton T. Stress and GABAA receptors. J Neurochem 2010; 112:1115-1130.
18. Nakhjiri E, Saboory E, Roshan-Milani S, Rasmi Y, Khalafkhani D. Effect of prenatal restraint stress and morphine co-administration on plasma vasopressin concentration and anxiety behaviors in adult rat offspring. Stress 2017; 20:205-211.
19. Jin Y, Korol SV, Jin Z, Barg S, Birnir B. In intact islets interstitial GABA activates GABAA receptors that generate tonic currents in α-cells. PloS one 2013; 8:e67228.
20. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. methods 2001; 25:402-408.
21. Yuan JS, Reed A, Chen F, Stewart CN. Statistical analysis of real-time PCR data. BMC bioinformatics 2006; 7:85.
22. Gholami M, Saboory E, Zare S, Roshan-Milani S, Hajizadeh-Moghaddam A. The effect of dorsal hippocampal administration of nicotinic and muscarinic cholinergic ligands on pentylenetetrazol-induced generalized seizures in rats. Epilepsy Behav 2012; 25:244-249.
23. Gholipoor P, Saboory E, Roshan-Milani S, Fereidoni J. Effect of hyperthermia on histamine blood level and convulsive behavior in infant rats. Epilepsy Behav; 29:269-274.
24. Gerrow K, Triller A. GABAA receptor subunit composition and competition at synapses are tuned by GABAB receptor activity. Mol Cell Neurosci 2014; 60:97-107.
25. Mody I, Maguire J. The reciprocal regulation of stress hormones and GABAA receptors. Front Cell Neurosci 2012; 6:4.
26. Majewska MD, Harrison NL, Schwartz RD, Barker JL, Paul SM. Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor. Science 1986; 232:1004-1007.
27. Nin MS, Ferri MK, Couto-Pereira NS, Souza MF, Azeredo LA, Agnes G, et al. The effect of intra-nucleus accumbens administration of allopregnanolone on δ and γ2 GABAA receptor subunit mRNA expression in the hippocampus and on depressive-like and grooming behaviors in rats. Pharmacol Biochem Behav 2012; 103:359-366.
28. Follesa P, Serra M, Cagetti E, Pisu MG, Porta S, Floris S, et al. Allopregnanolone synthesis in cerebellar granule cells: roles in regulation of GABAA receptor expression and function during progesterone treatment and withdrawal. Mol Pharmacol 2000; 57:1262-1270.
29. Stone DJ, Walsh JP, Sebro R, Stevens R, Pantazopolous H, Benes FM. Effects of pre- and postnatal corticosterone exposure on the rat hippocampal GABA system. Hippocampus 2001; 11:492-507.
30. Yu Z-Y, Wang W, Fritschy J-M, Witte OW, Redecker C. Changes in neocortical and hippocampal GABAA receptor subunit distribution during brain maturation and aging. Brain Res 2006; 1099:73-81.
31. Gholami M, Saboory E, Roshan-Milani S. Proconvulsant effects of tramadol and morphine on pentylenetetrazol-induced seizures in adult rats using different routes of administration. Epilepsy Behav 2014; 36:90-96.
32. Heshmatian B, Roshan-Milani S, Saboory E. Prenatal acute stress attenuated epileptiform activities in neonate mice. Yakhteh 2010; 12:81-86.
33. Gholami M, Saboory E. Morphine exposure induces age-dependent alterations in pentylenetetrazole-induced epileptic behaviors in prepubertal rats. Dev Psychobiol 2013; 55:881-887.

Iranian Journal of Basic Medical Sciences
Volume 23, Issue 6
June 2020
Pages 724-729

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