Heat stress-induced memory impairment is associated with neuroinflammation in mice

Journal of Neuroinflammation

Myung Sook Oh⁴  Tae Hee Lee³  Hyo Geun Kim⁴  Minho Moon²  Wonil Lee¹ 

[1] Department of Life and Nanopharmaceutical Science, Graduate School and Kyung Hee East–West Pharmaceutical Research Institute, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea;Department of Biochemistry, College of Medicine, Konyang University, Daejeon 302-718, Republic of Korea;Department of Formulae Pharmacology, School of Oriental Medicine, Gachon University, 1342 Seongnamdae-ro, Sujeong-gu, Seongnam 461-701, Republic of Korea;Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea

关键词: Neuronal death;    Synaptic loss;    Neuroinflammation;    Cognition;    Thermal stress;    Heat stress;   

Others  :  1221984
DOI  :  10.1186/s12974-015-0324-6

 received in 2014-11-06, accepted in 2015-05-14,  发布年份 2015

【 摘 要 】

Background

Heat stress induces many pathophysiological responses and has a profound impact on brain structure. It has been demonstrated that exposure to high temperature induces cognitive impairment in experimental animals and humans. Although the effects of heat stress have long been studied, the mechanisms by which heat stress affects brain structure and cognition not well understood.

Methods

In our longitudinal study of mice exposed to heat over 7, 14, or 42 days, we found that heat stress time dependently impaired cognitive function as determined by Y-maze, passive avoidance, and novel object recognition tests. To elucidate the histological mechanism by which thermal stress inhibited cognitive abilities, we examined heat stress-induced inflammation in the hippocampus.

Results

In mice subjected to heat exposure, we found: 1) an increased number of glial fibrillary acid protein (GFAP)- and macrophage-1 antigen (Mac-1)-positive cells, 2) up-regulated nuclear factor (NF)-κB, a master regulator of inflammation, and 3) marked increases in cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and cytokine interleukin (IL)-1β and tumor necrosis factor (TNF)-α in the mouse hippocampus. We also observed that neuronal and synaptic densities were degenerated significantly in hippocampal regions after heat exposure, as determined by histological analysis of neuronal nuclei (NeuN), postsynaptic density protein 95 (PSD-95), and synaptophysin expression. Moreover, in heat-exposed mice, we found that the number of cells positive for doublecortin (DCX), a marker of neurogenesis, was significantly decreased compared with control mice. Finally, anti-inflammatory agent minocycline inhibited the heat stress-induced cognitive deficits and astogliosis in mice.

Conclusions

Together, these findings suggest that heat stress can lead to activation of glial cells and induction of inflammatory molecules in the hippocampus, which may act as causative factors for memory loss, neuronal death, and impaired adult neurogenesis.

【 授权许可】

   
2015 Lee et al.

【 图 表 】

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