Inactivation of Basolateral Amygdala Prevents Stress-Induced Astroglial Loss in the Prefrontal Cortex
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Repeated stress causes cognitive decline and decreases the expression of glial fibrillary acidic protein (GFAP)+ astroglial cells in the prefrontal cortex (PFC). The stress-induced alterations in astroglial density and morphology might significantly contribute to cognitive impairments. Apart from PFC, a key region involved in modulation of repercussions of stress is basolateral amygdala (BLA), which undergoes hypertrophy following chronic immobilization stress (CIS) and has intense reciprocal connections to the PFC. Interestingly, inactivation of BLA precludes stress-induced learning deficits. However, the modulatory role of BLA on CIS-induced alterations in GFAP+ astroglial density and associated learning deficits are presently unknown. Accordingly, we present two sets of experiments evaluating the effects of BLA inactivation either permanently or temporarily on CIS-induced changes in learning and astroglial expression in the PFC. CIS causes impairment in novel object recognition memory and astroglial loss in the PFC. In experiment I, we permanently inactivated the BLA by ibotenate lesion prior to CIS and observed a significant improvement in learning. Surprisingly, BLA lesion also prevented the stress-induced astroglial loss in the PFC. Furthermore, in the experiment II, we analyzed whether the effects of permanent inactivation could be mirrored by the temporary blockage of BLA specifically during stress. Interestingly, temporary inactivation of BLA mimics the effects of lesion. There was a notable prevention of learning impairment and astroglial loss in the PFC following BLA inactivation during stress. The present study emphasizes that stress-induced astroglial loss might contribute to cognitive deficits and modulation of BLA activity might be a viable strategy for management of stress-related PFC dysfunctions.
KeywordsChronic stress Inactivation of basolateral amygdala Prefrontal cortex Astroglial plasticity Cognitive deficits
Anterior cingulate cortex
Glial fibrillary acidic protein
Chronic immobilization stress
Novel object recognition
- HPA axis
Hypothalamic pituitary adrenal axis
Sunil Jamuna Tripathi was supported by a Senior Research Fellowship (File No. 09/490(0095)/2014-EMR-I) from the Council of Scientific and Industrial Research (CSIR), New Delhi, India. Suwarna Chakraborty was supported by a research fellowship (NIMH: A&E/C:PhD(NP):2013-14: SC) from the National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru, India. We acknowledge financial support from the Department of Biotechnology (DBT), Science and Engineering Research Board, Department of Science & Technology, Government of India (SERB-DST), New Delhi and National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru, India.
S.J.T., T.R.R., and B.S.S.R. conceptualized and designed the experiments; S.J.T. and S.C. performed the experiments and analyzed the data; B.N.S, T.R.R., and B.S.S.R. contributed to reagents/materials/analysis tools; and S.J.T., S.C., B.N.S, T.R.R., and B.S.S.R. wrote the manuscript.
Compliance with Ethical Standards
Conflict of Interest
The authors declare no conflict of interest.
- 2.Ramkumar K, Srikumar BN, Venkatasubramanian D, Siva R, Shankaranarayana Rao BS, Raju TR (2012) Reversal of stress-induced dendritic atrophy in the prefrontal cortex by intracranial self-stimulation. J Neural Transm (Vienna) 119(5):533–543Google Scholar
- 3.Pawlak R, Shankaranarayana Rao BS, Melchor JP, Chattarji S, McEwen B, Strickland S (2005) Tissue plasminogen activator and plasminogen mediate stress-induced decline of neuronal and cognitive functions in the mouse hippocampus. Proc Natl Acad Sci U S A 102(50):18201–18206PubMedPubMedCentralGoogle Scholar
- 4.Shilpa BM, Bhagya V, Harish G, Srinivas Bharath MM, Shankaranarayana Rao BS (2017) Environmental enrichment ameliorates chronic immobilisation stress-induced spatial learning deficits and restores the expression of BDNF, VEGF, GFAP and glucocorticoid receptors. Prog Neuro-Psychopharmacol Biol Psychiatry 76:88–100Google Scholar
- 5.Veena J, Srikumar BN, Raju TR, Shankaranarayana Rao BS (2009) Exposure to enriched environment restores the survival and differentiation of new born cells in the hippocampus and ameliorates depressive symptoms in chronically stressed rats. Neurosci Lett 455(3):178–182PubMedPubMedCentralGoogle Scholar
- 8.Wei J, Zhong P, Qin L, Tan T, Yan Z (2017) Chemicogenetic restoration of the prefrontal cortex to amygdala pathway ameliorates stress-induced deficits. Cereb Cortex. https://doi.org/10.1093/cercor/bhx104
- 37.Tripathi SJ, Chakraborty S, Srikumar BN, Raju TR, Shankaranarayana Rao BS (2017) Inactivation of basolateral amygdala prevents chronic immobilization stress-induced memory impairment and associated changes in corticosterone levels. Neurobiol Learn Mem 142(Pt B):218–229PubMedPubMedCentralGoogle Scholar
- 38.Paxinos G, Watson C (2006) The rat brain in stereotaxic coordinates. Academic Press, AmsterdamGoogle Scholar
- 39.Tripathi SJ, Chakraborty S, Srikumar BN, Raju TR, Shankaranarayana Rao BS (2017) Prevention of chronic immobilization stress-induced enhanced expression of glucocorticoid receptors in the prefrontal cortex by inactivation of basolateral amygdala. J Chem Neuroanat. https://doi.org/10.1016/j.jchemneu.2017.12.006
- 46.Abhijit S, Tripathi SJ, Bhagya V, Shankaranarayana Rao BS, Subramanyam MV, Asha Devi S (2018) Antioxidant action of grape seed polyphenols and aerobic exercise in improving neuronal number in the hippocampus is associated with decrease in lipid peroxidation and hydrogen peroxide in adult and middle-aged rats. Exp Gerontol 101:101–112PubMedPubMedCentralGoogle Scholar
- 49.Shankaranarayana Rao BS, Desiraju T, Raju TR (1993) Neuronal plasticity induced by self-stimulation rewarding experience in rats—a study on alteration in dendritic branching in pyramidal neurons of hippocampus and motor cortex. Brain Res 627(2):216–224Google Scholar
- 52.Gaskin S, Tardif M, Cole E, Piterkin P, Kayello L, Mumby DG (2010) Object familiarization and novel-object preference in rats. Behav Process 83(1):61–71Google Scholar
- 60.Sunanda, Shankaranarayana Rao BS, Raju TR (2000) Chronic restraint stress impairs acquisition and retention of spatial memory task in rats. Curr Sci 79(11):1581Google Scholar
- 61.Shankaranarayana Rao BS, Madhavi R, Sunanda RTR (2001) Complete reversal of dendritic atrophy in CA3 neurons of the hippocampus by rehabilitation in restraint stressed rats. Curr Sci 80:653–659Google Scholar
- 73.Miguel-Hidalgo JJ, Baucom C, Dilley G, Overholser JC, Meltzer HY, Stockmeier CA, Rajkowska G (2000) Glial fibrillary acidic protein immunoreactivity in the prefrontal cortex distinguishes younger from older adults in major depressive disorder. Biol Psychiatry 48(8):861–873PubMedPubMedCentralGoogle Scholar
- 78.Banasr M, Chowdhury GM, Terwilliger R, Newton SS, Duman RS, Behar KL, Sanacora G (2010) Glial pathology in an animal model of depression: reversal of stress-induced cellular, metabolic and behavioral deficits by the glutamate-modulating drug riluzole. Mol Psychiatry 15(5):501–511PubMedPubMedCentralGoogle Scholar