title: H2S Regulates Hypobaric Hypoxia-Induced Early Glio-Vascular Dysfunction and Neuro-Pathophysiological Effects.
abstract: Hypobaric Hypoxia (HH) is an established risk factor for various neuro-physiological perturbations including cognitive impairment. The origin and mechanistic basis of such responses however remain elusive. We here combined systems level analysis with classical neuro-physiological approaches, in a rat model system, to understand pathological responses of brain to HH. Unbiased 'statistical co-expression networks' generated utilizing temporal, differential transcriptome signatures of hippocampus-centrally involved in regulating cognition-implicated perturbation of Glio-Vascular homeostasis during early responses to HH, with concurrent modulation of vasomodulatory, hemostatic and proteolytic processes. Further, multiple lines of experimental evidence from ultra-structural, immuno-histological, substrate-zymography and barrier function studies unambiguously supported this proposition. Interestingly, we show a significant lowering of H2S levels in the brain, under chronic HH conditions. This phenomenon functionally impacted hypoxia-induced modulation of cerebral blood flow (hypoxic autoregulation) besides perturbing the strength of functional hyperemia responses. The augmentation of H2S levels, during HH conditions, remarkably preserved Glio-Vascular homeostasis and key neuro-physiological functions (cerebral blood flow, functional hyperemia and spatial memory) besides curtailing HH-induced neuronal apoptosis in hippocampus. Our data thus revealed causal role of H2S during HH-induced early Glio-Vascular dysfunction and consequent cognitive impairment.
authors.affiliation: Neurobiology Division, Defence Institute of Physiology and Allied Sciences (DIPAS), DRDO, Delhi 110054, India.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Kumar
authors.affiliation: Peptide and Proteomics Division, Defence Institute of Physiology and Allied Sciences (DIPAS), DRDO, Delhi 110054, India.
authors.forename: Aastha
authors.initials: A
authors.lastname: Chhabra
authors.affiliation: Peptide and Proteomics Division, Defence Institute of Physiology and Allied Sciences (DIPAS), DRDO, Delhi 110054, India.
authors.forename: Shalini
authors.initials: S
authors.lastname: Mishra
authors.affiliation: Immunology Group, International Center for Genetic Engineering and Biotechnology (ICGEB), Aruna Asaf Ali Marg, New Delhi-110067, India.
authors.forename: Haroon
authors.initials: H
authors.lastname: Kalam
authors.affiliation: Immunology Group, International Center for Genetic Engineering and Biotechnology (ICGEB), Aruna Asaf Ali Marg, New Delhi-110067, India.
authors.forename: Dhiraj
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Peptide and Proteomics Division, Defence Institute of Physiology and Allied Sciences (DIPAS), DRDO, Delhi 110054, India.
authors.forename: Ramniwas
authors.initials: R
authors.lastname: Meena
authors.affiliation: Peptide and Proteomics Division, Defence Institute of Physiology and Allied Sciences (DIPAS), DRDO, Delhi 110054, India.
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Ahmad
authors.affiliation: Peptide and Proteomics Division, Defence Institute of Physiology and Allied Sciences (DIPAS), DRDO, Delhi 110054, India.
authors.forename: Kalpana
authors.initials: K
authors.lastname: Bhargava
authors.affiliation: Neurobiology Division, Defence Institute of Physiology and Allied Sciences (DIPAS), DRDO, Delhi 110054, India.
authors.forename: Dipti N
authors.initials: DN
authors.lastname: Prasad
authors.affiliation: Peptide and Proteomics Division, Defence Institute of Physiology and Allied Sciences (DIPAS), DRDO, Delhi 110054, India. Electronic address: manishks77@gmail.com.
authors.forename: Manish
authors.initials: M
authors.lastname: Sharma
mesh_terms: D000532:Altitude Sickness / Q000150:complications / Q000235:genetics*; D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects; D060825:Cognitive Dysfunction / Q000188:drug therapy* / Q000235:genetics; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects; D006624:Hippocampus / Q000098:blood supply* / Q000737:chemistry / Q000187:drug effects; D006801:Humans; D006862:Hydrogen Sulfide / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D051381:Rats
chemical_list: D006862:Hydrogen Sulfide
keywords: Co-expression networks; Cognition; Glio-Vascular Unit; H(2)S; Hypobaric Hypoxia; Neuro-Vascular Unit