Hypobaric hypoxia-induced dendritic atrophy of hippocampal neurons is associated with cognitive impairment in adult rats

A. D.J. Titus, B. S. Shankaranarayana Rao, H. N. Harsha, K. Ramkumar, B. N. Srikumar, S. B. Singh, S. Chattarji, T. R. Raju

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109 Scopus citations

Abstract

Simulated hypobaric hypoxia (HBH), resembling high altitude hypoxia severely affects the CNS and results in several physiological changes. The hippocampus is closely associated with learning and memory and an insult to this region affects cognition. Previous studies suggest that rapid or prolonged exposures to HBH are associated with psychomotor and cognitive impairments. The defense personnel, mountain climbers and rescue teams are exposed to such harsh environment and thus it demands a systematic study emphasizing the subtle effects of such extreme environments on cognitive function. Accordingly, this study evaluated the effect of hypobaric hypoxia on structural changes in the principal neurons of the hippocampus and learning in eight-arm radial maze. Adult male Wistar rats, subjected to simulated hypobaric hypoxia equivalent to an altitude of 6000 m for a period of 2 or 7 days, in a hypoxic chamber served as hypoxic group (HY). Rats housed in a similar chamber for the same period of time, without hypoxic exposure served as sham control (SC), while normal control (NC) group of rats were housed in standard laboratory conditions. The dendritic morphology of neurons in cornu ammonis region 1 (CA1) and cornu ammonis region 3 (CA3) was studied in Golgi-impregnated hippocampal sections. Exposure for 2 days to hypobaric hypoxia had minimal deleterious effects on the CA1 pyramidal neurons, while exposure for 7 days resulted in a significant decrease in the number of branching points, intersections and dendritic length. Unlike the CA1 pyramidal neurons, the CA3 neurons exhibited dendritic atrophy following both 2 and 7 days of hypoxic exposure. Further, hippocampal-dependent spatial learning was affected marginally following 2 day exposure, while 7 day exposure severely affected learning of the partially baited radial arm maze task. Our study suggests that dendritic atrophy in the hippocampus on exposure to HBH could be one of the bases for the cognitive deficits exhibited under such conditions.

Original languageEnglish (US)
Pages (from-to)265-278
Number of pages14
JournalNeuroscience
Volume145
Issue number1
DOIs
StatePublished - Mar 2 2007
Externally publishedYes

Bibliographical note

Funding Information:
Financial support by Defence Research and Developmental Organisation (DRDO), Government of India and National Institute of Mental Health and Neuro Sciences (NIMHANS) is greatly acknowledged.

Keywords

  • Golgi-impregnation
  • cognitive deficits
  • high altitude hypoxia
  • neuronal plasticity
  • radial arm maze
  • spatial learning

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