Hypobaric hypoxia impairs cued and contextual fear memory in rats

Kumari, Pooja; Kauser, Hina; Wadhwa, Meetu; Roy, Koustav; Alam, Shahid; Sahu, Shilpi; Kishore, Krishna; Ray, Koushik; Panjwani, Usha

doi:10.1016/j.brainres.2018.04.026

Cited by 16 publications

(10 citation statements)

References 45 publications

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“…Neurodegeneration in both the amygdala and hippocampus after HH exposure have well established [18,47] which make rats vulnerable to anxiety. During many psychiatric disease states, anxiety and social de cits are co-expressed [48,49,50]. Our observation that HH exposure for 7days severely affects the social interaction behavior and induce anxiety like behavior in rats provided a unique opportunity to explore underlying molecular mechanism in HH.…”

Section: Discussionmentioning

confidence: 89%

COX-1/EP1R Inhibition Ameliorate Deficits in Adult Neurogenesis and Social Interaction via Alleviating NLRP3/ IL-1β Activation During Hypobaric Hypoxia

Chauhan¹,

Kumar²,

Roy³

et al. 2020

Preprint

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BackgroundLow oxygen environments like hypobaric hypoxia (HH) are common nodes to various diseases: characterized by neuroinflammation, which is detrimental to the structural and functional aspects of hippocampal circuitry. Various hypoxic conditions also lead to elevation of NLRP3 mediated neuroinflammation that may contribute to cognitive deficits. Components of neurogenic niches like microglia and astrocyte are largely affected by neuroinflammation; however, a systematic investigation of the impact of NLRP3 mediated neuroinflammation on components of neurogenic niche during hypoxia (HH) remains elusive. MethodsIn this study, we simulated cerebral hypoxia via decreasing partial pressure of oxygen(HH). The effect of hypobaric hypoxic (1, 3 and 7 day at 25000 ft) on social memory, anxiety, adult neurogenesis change in the inflammatory milieu in DG was explored in detail. We explored the efficacy of COX-1 inhibitor (Valery salicylate, 5mg/kg/day,i.p), and EP1R antagonist (SC19220, 1mg/kg/day,i.p) on NLRP3 mediated neuroinflammation and associated maladies during HH. ResultsWe observed that HH exposure induced alteration in social and anxiety-like behavior post 7 day exposure along with perturbation in levels of BDNF, Serotonin and adult neurogenesis in the DG right from day 1. Moreover, significant elevated NLRP3, caspase-1, and IL-1β levels are observed during HH from day 1. Concomitantly, a notable increase in the COX-1/EP1 pathway in both activated microglia and astrocyte in DG was evident after 3HH exposure. Pharmacological COX-1 inhibitor and EP1 antagonist counteract the detrimental effects of HH exposure on social memory, adult neurogenesis, and NLRP3 inflammasome induction. ConclusionsThus, our data showed induction of the COX-1/EP1 pathway in glial cells is detrimental to adult neurogenesis and social memory, raising possibility that the COX-1/EP1 pathway as a plausible target for inflammasome related neurogenesis impairment.

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Section: Discussionmentioning

confidence: 89%

COX-1/EP1R Inhibition Ameliorate Deficits in Adult Neurogenesis and Social Interaction via Alleviating NLRP3/ IL-1β Activation During Hypobaric Hypoxia

Chauhan¹,

Kumar²,

Roy³

et al. 2020

Preprint

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“…Exposure to HA has been shown to cause cognitive deficits 14,19,20,22,23 . We used the hippocampal fear conditioning paradigm to assess cognitive function in CEHA mice compared to SL controls.…”

Section: Resultsmentioning

confidence: 99%

“…A recent study by Kumari et al . 20 found that rats exposed to 25,000 ft had significant deficits in cued and contextual fear acquisition, which peaked at seven days. In addition, other researchers have shown that rats kept at 6100 m for seven days had impairment in spatial memory 28 .…”

Section: Discussionmentioning

confidence: 96%

“…It has been shown that CEHA and its consequent hypoxic/hypobaric effects are capable of inducing changes in motor behavior along with reduction in cognitive performance due to maladaptive changes of the CNS 13–18 . Animal studies have shown that CEHA is capable of inducing changes in motor and cognitive behavior suggesting that the brain continually adapts to the stress caused by CEHA 19,20 . In Mount Everest climbers, cognitive and linguistic performance were assessed at different time points, and it was found that there were more errors in speech at increased altitudes, which, itself, is an indication of cognitive deficit reflecting degraded cortical and basal ganglia activities 14 .…”

Section: Introductionmentioning

confidence: 99%

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Chronic Exposure to High Altitude: Synaptic, Astroglial and Memory Changes

Sharma

Cramer

Perry

et al. 2019

Sci Rep

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Long-term operations carried out at high altitude (HA) by military personnel, pilots, and astronauts may trigger health complications. In particular, chronic exposure to high altitude (CEHA) has been associated with deficits in cognitive function. In this study, we found that mice exposed to chronic HA (5000 m for 12 weeks) exhibited deficits in learning and memory associated with hippocampal function and were linked with changes in the expression of synaptic proteins across various regions of the brain. Specifically, we found decreased levels of synaptophysin (SYP) (p < 0.05) and spinophilin (SPH) (p < 0.05) in the olfactory cortex, post synaptic density−95 (PSD-95) (p < 0.05), growth associated protein 43 (GAP43) (p < 0.05), glial fibrillary acidic protein (GFAP) (p < 0.05) in the cerebellum, and SYP (p < 0.05) and PSD-95 (p < 0.05) in the brainstem. Ultrastructural analyses of synaptic density and morphology in the hippocampus did not reveal any differences in CEHA mice compared to SL mice. Our data are novel and suggest that CEHA exposure leads to cognitive impairment in conjunction with neuroanatomically-based molecular changes in synaptic protein levels and astroglial cell marker in a region specific manner. We hypothesize that these new findings are part of highly complex molecular and neuroplasticity mechanisms underlying neuroadaptation response that occurs in brains when chronically exposed to HA.

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“…An exuberant excess of spines having an immature, long and thin morphology is a well described phenotype related with mental impairment (20). The hippocampus is primarily responsible for learning-memory process, and its CA1 region is closely related to short-term memory and spatial memory, and is the most sensitive to hypoxia-induced damage (2,21,22). Synaptic plasticity in the hippocampus is an established neurobiological basis for learning and memory.…”

Section: Discussionmentioning

confidence: 99%

Cirbp-PSD95 Axis Protects Against Hypobaric Hypoxia-Induced Aberrant Morphology of Hippocampal Dendritic Spines and Cognitive Deficits

Zhang

Liu

et al. 2020

Preprint

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Hypobaric hypoxia (HH) is a typical characteristic of high altitude environment and causes a spectrum of pathophysiological effects, including headaches, gliovascular dysfunction and cognitive slowing. Here, we sought to understand the mechanisms underlying cognitive deficits under HH exposure. Our results showed that HH exposure impaired cognitive function and suppressed dendritic spine density accompanied with increased neck length in both basal and apical hippocampal CA1 region neurons. The expression of PSD95, a critical synaptic scaffolding molecule, is down-regulated by hypoxia exposure and post-transcriptionally controlled by cold-inducible RNA-binding protein (Cirbp) through 3’-UTR region binding. PSD95 expressing alleviates hypoxia-induced neuron dendritic spine plasticity abnormality and memory impairment. Moreover, overexpressed Cirbp in hippocampus rescues hypoxia-induced loss of PSD95 and attenuates hypoxia-induced dendritic spine injury and cognitive outcomes. Thus, our findings reveal a novel mechanism where Cirbp-PSD-95 axis appears to play a key role in hypoxia-induced cognitive abilities impairment in brain.

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Hypobaric hypoxia impairs cued and contextual fear memory in rats

Cited by 16 publications

References 45 publications

COX-1/EP1R Inhibition Ameliorate Deficits in Adult Neurogenesis and Social Interaction via Alleviating NLRP3/ IL-1β Activation During Hypobaric Hypoxia

COX-1/EP1R Inhibition Ameliorate Deficits in Adult Neurogenesis and Social Interaction via Alleviating NLRP3/ IL-1β Activation During Hypobaric Hypoxia

Chronic Exposure to High Altitude: Synaptic, Astroglial and Memory Changes

Cirbp-PSD95 Axis Protects Against Hypobaric Hypoxia-Induced Aberrant Morphology of Hippocampal Dendritic Spines and Cognitive Deficits

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Hypobaric hypoxia impairs cued and contextual fear memory in rats

Cited by 16 publications

References 45 publications

COX-1/EP1R&nbsp;Inhibition Ameliorate Deficits in Adult Neurogenesis and Social Interaction via Alleviating NLRP3/ IL-1β Activation During Hypobaric Hypoxia

COX-1/EP1R&nbsp;Inhibition Ameliorate Deficits in Adult Neurogenesis and Social Interaction via Alleviating NLRP3/ IL-1β Activation During Hypobaric Hypoxia

Chronic Exposure to High Altitude: Synaptic, Astroglial and Memory Changes

Cirbp-PSD95 Axis Protects Against Hypobaric Hypoxia-Induced Aberrant Morphology of Hippocampal Dendritic Spines and Cognitive Deficits

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COX-1/EP1R Inhibition Ameliorate Deficits in Adult Neurogenesis and Social Interaction via Alleviating NLRP3/ IL-1β Activation During Hypobaric Hypoxia

COX-1/EP1R Inhibition Ameliorate Deficits in Adult Neurogenesis and Social Interaction via Alleviating NLRP3/ IL-1β Activation During Hypobaric Hypoxia