Effects of maternal stress on Reelin signaling and migration of GABAergic interneurons in the prefrontal cortex of postnatal rats
Keywords:
maternal stress, Reelin signaling, GABAergic interneurons, prefrontal cortexAbstract
Stress during pregnancy affects fetal brain development and increases the risk of subsequent neuropsychiatric diseases. The prefrontal cortex (PFC) plays important role in higher cognition and its impairment is associated with neuropsychiatric disorders. GABAergic interneurons are the last group of neurons that migrate into the cortex and plays a crucial role in modulating cortical output for proper sensory gating function and cognition. Reelin is an extracellular matrix protein that plays role in neural migration and its dysfunction causes the abnormal positioning of neurons in the cortex. Importantly, both the dysfunction of reelin and the abnormal function of GABAergic interneurons are associated with the pathology of neuropsychiatric disorders. However, it is still not clear how maternal stress alters GABAergic interneurons migration in the brains of the rat pups. The present study investigates the effect of MS on reelin signaling and the migration of GABAergic interneurons in the PFC among the rat pups. The pregnant rats were divided into two groups; maternal stress (MS) and the control group. The distribution of GABAergic interneurons and the expression level signaling proteins for the reelin pathway were measured and compared between groups. at a statistically significant level of 0.05. The results revealed that MS significantly decreased GABA-immunopositive cells in the PFC of rat pups as compared to the control. Besides, MS temporarily increases reelin expression in the PFC of newborn pups, but later decreased at postnatal day (P)7. In addition, MS-induced a significant decrease in VLDLR and Dab1 expression in the PFC of rat pups at P7-P14. Altogether, the results indicated that MS has long-term effects on GABAergic interneurons migration in the prefrontal cortex of rat pups and the mechanism might be related to the dysfunction of reelin signaling. In conclusion, reelin dysfunction and abnormal positioning of GABAergic interneurons might be the mechanism that links early-life stress and the emergence of neuropsychiatric disorders later in life.
References
2. King S, Laplante David P. The effects of prenatal maternal stress on children’s cognitive development: Project Ice Storm. Stress 2005;8:35-45.
3. Talge Nicole M, Neal C, Glover V. Antenatal maternal stress and long-term effects on
child neurodevelopment: how and why? J Child Psychol Psychiatry 2007;48:245-61.
4. Grizenko N, Rajabieh Shayan Y, Polotskaia A, et al. Relation of maternal stress during pregnancy to symptom severity and response to treatment in children with ADHD. J Psychiatry Neurosci 2008;33:10-6.
5. Huttunen M.O, P Niskanen. Prenatal loss of father and psychiatric disorders. Arch Gen Psychiatry 1978;35:429-31.
6. Barros Virginia G, Duhalde-Vega M, Caltana L, et al. Astrocyte-neuron vulnerability to
prenatal stress in the adult rat brain.J Neurosci Res 2006;83:787-800.
7. Vyas A, Mitra R, Rao Shankaranarayana B S, et al. Chronic stress induces contrasting patterns of dendritic remodeling in hippocampal and amygdaloid neurons. J Neurosci 2002;22:6810-8.
8. Deutch A Y, Lee M C, Gillham M H, et al. Stress selectively increases fos protein in dopamine neurons innervating the prefrontal cortex. Cereb Cortex 1991; 1:273-92.
9. Alexander G E, Goldman P S. Functional development of the dorsolateral prefrontal cortex: an analysis utilizing reversible cryogenic depression. Brain Res 1978;143:233-49.
10. Gonzalez-Burgos G, Lewis D A. NMDA Receptor Hypofunction, ParvalbuminPositive Neurons, and Cortical Gamma Oscillations in Schizophrenia. Schizophrenia Bulletin 2012;38:950-7.
11. Herz J, Chen Y. Reelin, lipoprotein receptors and synaptic plasticity. Nat Rev Neurosci 2006;7:850-9.
12. Fatemi SH, Reelin glycoprotein: structure, biology and roles in health and disease. Mol Psychiatry 2005;10:251-7.
13. Dlugosz P, Nimpf J. Nimpf, The Reelin Receptors Apolipoprotein E receptor 2 (ApoER2) and VLDL Receptor. Int J Mol Sci 2018;19:3090.
14. Teixeira Cátia M, Martín Eduardo D, SahúnI, et al. Overexpression of Reelin prevents the manifestation of behavioral phenotypes related to schizophrenia and bipolar disorder. Neuropsychopharmacology 2011;36:2395-405.
15. Ovadia G, Shifman S. The genetic variation of RELN expression in schizophrenia and bipolar disorder. PLoS One 2011;6:e19955.
16. Knuesel I. Reelin-mediated signaling in neuropsychiatric and neurodegenerative diseases. Prog Neurobiol 2010;91:257-74.
17. Botella-López A, Burgaya F, Gavín R, et al. Reelin expression and glycosylation patterns are altered in Alzheimer’s disease. Proc Natl Acad Sci U S A 2006; 103:5573-8.
18. Negrón-Oyarzo I, Lara-Vásquez A, PalaciosGarcía I, et al. Schizophrenia and reelin: a model based on prenatal stress to study epigenetics, brain development and behavior. Biol Res 2016;49:16.
19. Folsom D T, Fatemi H S. The involvement of Reelin in neurodevelopmental disorders. Neuropharmacology 2013; 68:122-35.
20. Hack I, Bancila M, Loulier K, et al. Reelin is a detachment signal in tangential chainmigration during postnatal neurogenesis.mNat Neurosci 2002;5:939-45.
21. Hevner F R, Daza R A M, Englund C, et al. Postnatal shifts of interneuron position in
the neocortex of normal and reeler mice: evidence for inward radial migration. Neuroscience 2004;124:605-18.
22. Zuena R A, Mairesse J, Casolini P, et al. Prenatal restraint stress generates two distinct behavioral and neurochemical profiles in male and female rats. PLoS One 2008;3:e2170.
23. Gutiérrez-Rojas C, Pascual R, Bustamante C. Prenatal stress alters the behavior and dendritic morphology of the medial orbitofrontal cortex in mouse offspring during lactation. Int J Dev Neurosci 2013;31:505-11.
24. Buynitsky T, Mostofsky I D. Restraint stress in biobehavioral research: Recent developments. Neurosci Biobehav Rev 2009;33:1089-98.
25. Fride E, Weinstock M. The effects of prenatal exposure to predictable or unpredictable stress on early development in the rat. Dev Psychobiol 1984;17:651-60.
26. Crandall E J, Hackett E H, Tobet A S, et al. Cocaine exposure decreases GABA neuron migration from the ganglionic eminence to the cerebral cortex in embryonic mice. Cereb Cortex 2004; 14:665-75.
27. Stevens E H, Su T, Yanagawa Y, et al. Prenatal stress delays inhibitory neuron progenitor migration in the developing neocortex. Psychoneuroendocrinology 2013;38:509-21.
28. Uchida T, Furukawa T, Iwata S, et al. Selective loss of parvalbumin-positive GABAergic interneurons in the cerebral cortex of maternally stressed Gad1- heterozygous mouse offspring. Transl Psychiatry 2014;4:e371.
29. Lussier J S, Stevens E H. Delays in GABAergic interneuron development and behavioral inhibition after prenatal stress. Dev Neurobiol 2016;76:1078-91.
30. Gogolla N, Leblanc J J, Quast B K, et al. Common circuit defect of excitatoryinhibitory balance in mouse models of autism. J Neurodev Disord 2009;1:172-81.
31. Addington M A, Gornick M, Duckworth J, et al. GAD1 (2q31.1), which encodes glutamic acid decarboxylase (GAD67), is associated with childhood-onset schizophrenia and cortical gray matter
volume loss. Mol Psychiatry 2005;10:581-8.
32. Hatanaka Y, Zhu Y, Torigoe M, et al. From migration to settlement: the pathways, migration modes and dynamics of neurons in the developing brain. Proc Jpn Acad Ser B Phys Biol Sci 2016;92:1-19.
33. Hevner F R, Neogi T, Englund C, et al. Cajal-Retzius cells in the mouse: transcription factors, neurotransmitters, and birthdays suggest a pallial origin. Brain Res Dev Brain Res 2003;141:39-53.
34. Arimitsu N, Takai K, Fujiwara N, et al. Roles of Reelin/Disabled1 pathway on functional
recovery of hemiplegic mice after neural cell transplantation; Reelin promotes migration toward motor cortex and maturation to motoneurons of neural grafts. Exp Neurol 2019;320:112970.
35. Chameau P, Inta D, Vitalis T, et al. The N-terminal region of reelin regulates postnatal dendritic maturation of cortical pyramidal neurons. Proc Natl Acad Sci U S A 2009;106:7227-32.
36. Matrisciano F, Tueting P, Dalal I, et al. Epigenetic modifications of GABAergic interneurons are associated with the schizophrenia-like phenotype induced by prenatal stress in mice. Neuropharmacology 2013;68:184-94.
37. Palacios-García I, Lara-Vásquez A, Montiel F J, et al. Prenatal stress down-regulates Reelin expression by methylation of its promoter and induces adult behavioral impairments in rats. PLoS One 2015; 10:e0117680.
38. Impagnatiello F, Guidotti R A, Pesold C, et al. A decrease of reelin expression as a putative vulnerability factor in schizophrenia. Proc Natl Acad Sci U S A 1998;95:15718-23.
