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Molecular Basis of Sex Difference in Neuroprotection induced by Hypoxia Preconditioning in Zebrafish.

Abstract：

:Hypoxia, the major cause of ischemic injury, leads to debilitating disease in infants via birth asphyxia and cerebral palsy, whereas in adults via heart attack and stroke. A widespread, natural protective phenomenon termed 'hypoxic preconditioning' (PH) occurs when prior exposures to hypoxia eventually result in robust hypoxia resistance. Accordingly, we have developed and optimized a novel model of hypoxic preconditioning in adult zebrafish to mimic the tolerance of mini stroke(s) in human, which appears to protect against the severe damage inflicted by a major stroke event. Here, we observed a remarkable difference in the progression pattern of neuroprotection between preconditioning hypoxia followed by acute hypoxia (PH) group, and acute hypoxia (AH) only group, with noticeable sex difference when compared with normoxia behaviour upon recovery. Since gender difference has been reported in stroke risk factors and disease history, it was pertinent to investigate whether any such sex difference also exists in PH's protective mechanism against acute ischemic stroke. In order to elucidate the neural molecular mechanisms behind sex difference in neuroprotection induced by PH, a high throughput proteomics approach utilizing iTRAQ was performed, followed by protein enrichment analysis using ingenuity pathway analysis (IPA) tool. Out of thousands of significantly altered proteins in zebrafish brain, the ones having critical role either in neuroglial proliferation/differentiation or neurotrophic functions were validated by analyzing their expression levels in preconditioned (PH), acute hypoxia (AH), and normoxia groups. The data indicate that female zebrafish brains are more protected against the severity of AH when exposed to the hypoxic preconditioning. The study also sheds light on the involvement of many signalling pathways underlying sex difference in preconditioning-induced neuroprotective mechanism, which can be further validated for the therapeutic approach.

journal_name

Mol Neurobiol

journal_title

Molecular neurobiology

authors

Das T,Soren K,Yerasi M,Kamle A,Kumar A,Chakravarty S

doi

10.1007/s12035-020-02091-1

subject

Has Abstract

pub_date

2020-12-01 00:00:00

pages

5177-5192

issue

12

eissn

0893-7648

issn

1559-1182

pii

10.1007/s12035-020-02091-1

journal_volume

57

pub_type

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