Abstract
Whereas brief acute or intermittent episodes of hypoxia have been shown to exert a protective role in the central nervous system and to stimulate neurogenesis, other studies suggest that early hypoxia may constitute a risk factor that influences the future development of mental disorders. We therefore investigated the effects of a neonatal “conditioning-like” hypoxia (100% N2, 5 min) on the brain and the cognitive outcomes of rats until 720 days of age (physiologic senescence). We confirmed that such a short hypoxia led to brain neurogenesis within the ensuing weeks, along with reduced apoptosis in the hippocampus involving activation of Erk1/2 and repression of p38 and death-associated protein (DAP) kinase. At 21 days of age, increased thicknesses and cell densities were recorded in various subregions, with strong synapsin activation. During aging, previous exposure to neonatal hypoxia was associated with enhanced memory retrieval scores specifically in males, better preservation of their brain integrity than controls, reduced age-related apoptosis, larger hippocampal cell layers, and higher expression of glutamatergic and GABAergic markers. These changes were accompanied with a marked expression of synapsin proteins, mainly of their phosphorylated active forms which constitute major players of synapse function and plasticity, and with increases of their key regulators, i.e. Erk1/2, the transcription factor EGR-1/Zif-268 and Src kinase. Moreover, the significantly higher interactions between PSD-95 scaffolding protein and NMDA receptors measured in the hippocampus of 720-day-old male animals strengthen the conclusion of increased synaptic functional activity and plasticity associated with neonatal hypoxia. Thus, early non-injurious hypoxia may trigger beneficial long term effects conferring higher resistance to senescence in aged male rats, with a better preservation of cognitive functions.
Highlights
Adverse environmental conditions during early development have been shown to influence health throughout life [1,2,3]
If sustained neonatal hypoxia/ischemia remains a major cause of brain injury and neurological disabilities, brief acute or intermittent episodes of hypoxia have been shown to exert a protective role in the central nervous system
Short-term Effects of Transient Neonatal Hypoxia In these experiments, since no significant differences were found between males and females (ANOVA), results were retrospectively pooled across sex
Summary
Adverse environmental conditions during early development have been shown to influence health throughout life [1,2,3]. Effects of the early cues on ensuing disease risk are not limited to the intrauterine conditions, since the postnatal environment may influence health outcome and subsequent brain functioning. Neuroadaptations and plasticity may include structural reactions (e.g., neurogenesis or cell death) and/or functional modifications in sensitive brain regions (e.g., long-term potentiation (LTP), long-term depression (LTD), reorganization of synaptic protein dynamics etc.). In this respect, exposure to transient oxygen deprivation frequently occurs around birth. The changes triggered in the brain stimulated by ‘‘pathologic’’ neurogenesis may lead to abnormal communications in exquisitely regulated neural networks This could in turn cause mental diseases, altered cognitive functions or premature brain aging [15]. A particular attention should be paid to the relative distribution of the different neuronal phenotypes that constitute brain circuits and govern the balance between excitatory and inhibitory connections [16,17,18,19]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
