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

Lee W, Moon M, Kim HG, Lee TH, Oh MS - J Neuroinflammation (2015)

Bottom Line: It has been demonstrated that exposure to high temperature induces cognitive impairment in experimental animals and humans.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.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.

View Article: PubMed Central - PubMed

Affiliation: 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. wonil@khu.ac.kr.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Effects of anti-inflammatory agent on heat-stress-induced memory loss and astrogliosis. (a) Cognitive function was assessed using a passive avoidance task after heat exposure and minocycline treatment. Columns represent the latency period for entering the dark box in the acquisition test and in the retention test, 24 h later. (b) The astrogliosis was analyzed and determined using glial fibrillary acidic protein (GFAP) staining. Quantification of GFAP-stained cells was performed by measuring the area fraction of GFAP-immunoreactive cells/areas in the CA3 of the hippocampus. Scale bar = 50 μm. Values are expressed as means ± S.E.M. *** p < 0.001 indicates that the mean value was significantly different from the control group
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4465309&req=5

Fig11: Effects of anti-inflammatory agent on heat-stress-induced memory loss and astrogliosis. (a) Cognitive function was assessed using a passive avoidance task after heat exposure and minocycline treatment. Columns represent the latency period for entering the dark box in the acquisition test and in the retention test, 24 h later. (b) The astrogliosis was analyzed and determined using glial fibrillary acidic protein (GFAP) staining. Quantification of GFAP-stained cells was performed by measuring the area fraction of GFAP-immunoreactive cells/areas in the CA3 of the hippocampus. Scale bar = 50 μm. Values are expressed as means ± S.E.M. *** p < 0.001 indicates that the mean value was significantly different from the control group

Mentions: To clearly examine the relationship with inflammation and cognitive function, we treated heat-stressed animals with anti-inflammatory agent minocycline. We determined heat-induced cognitive deficits and minocycline-induced inhibition of memory loss using a passive avoidance test. The retention time of the heat-exposed and minocycline-treated group was increased compared with heat-exposed and vehicle-treated group (Fig. 11a). No differences were observed in latency time during the acquisition trials among any of the groups (Fig. 11a). Next, we investigated the effect of minocycline on heat stress-induced glial activation in the hippocampus by immunohistochemistry using antibody against GFAP. Immunohistochemical analysis revealed that the number of GFAP-stained astrocytes was significantly decreased in the hippocampus following heat exposure and minocycline treatment, compared with heat-exposure and vehicle-treatment (Fig. 11b). Our results suggest that heat stress-induced memory loss can be mediated by neuroinflammation in the hippocampus.Fig. 11


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

Lee W, Moon M, Kim HG, Lee TH, Oh MS - J Neuroinflammation (2015)

Effects of anti-inflammatory agent on heat-stress-induced memory loss and astrogliosis. (a) Cognitive function was assessed using a passive avoidance task after heat exposure and minocycline treatment. Columns represent the latency period for entering the dark box in the acquisition test and in the retention test, 24 h later. (b) The astrogliosis was analyzed and determined using glial fibrillary acidic protein (GFAP) staining. Quantification of GFAP-stained cells was performed by measuring the area fraction of GFAP-immunoreactive cells/areas in the CA3 of the hippocampus. Scale bar = 50 μm. Values are expressed as means ± S.E.M. *** p < 0.001 indicates that the mean value was significantly different from the control group
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4465309&req=5

Fig11: Effects of anti-inflammatory agent on heat-stress-induced memory loss and astrogliosis. (a) Cognitive function was assessed using a passive avoidance task after heat exposure and minocycline treatment. Columns represent the latency period for entering the dark box in the acquisition test and in the retention test, 24 h later. (b) The astrogliosis was analyzed and determined using glial fibrillary acidic protein (GFAP) staining. Quantification of GFAP-stained cells was performed by measuring the area fraction of GFAP-immunoreactive cells/areas in the CA3 of the hippocampus. Scale bar = 50 μm. Values are expressed as means ± S.E.M. *** p < 0.001 indicates that the mean value was significantly different from the control group
Mentions: To clearly examine the relationship with inflammation and cognitive function, we treated heat-stressed animals with anti-inflammatory agent minocycline. We determined heat-induced cognitive deficits and minocycline-induced inhibition of memory loss using a passive avoidance test. The retention time of the heat-exposed and minocycline-treated group was increased compared with heat-exposed and vehicle-treated group (Fig. 11a). No differences were observed in latency time during the acquisition trials among any of the groups (Fig. 11a). Next, we investigated the effect of minocycline on heat stress-induced glial activation in the hippocampus by immunohistochemistry using antibody against GFAP. Immunohistochemical analysis revealed that the number of GFAP-stained astrocytes was significantly decreased in the hippocampus following heat exposure and minocycline treatment, compared with heat-exposure and vehicle-treatment (Fig. 11b). Our results suggest that heat stress-induced memory loss can be mediated by neuroinflammation in the hippocampus.Fig. 11

Bottom Line: It has been demonstrated that exposure to high temperature induces cognitive impairment in experimental animals and humans.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.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.

View Article: PubMed Central - PubMed

Affiliation: 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. wonil@khu.ac.kr.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus