TY - JOUR
T1 - Deficiency in EP4 Receptor–Associated Protein Ameliorates Abnormal Anxiety-Like Behavior and Brain Inflammation in a Mouse Model of Alzheimer Disease
AU - Fujikawa, Risako
AU - Higuchi, Sei
AU - Nakatsuji, Masato
AU - Yasui, Mika
AU - Ikedo, Taichi
AU - Nagata, Manabu
AU - Hayashi, Kosuke
AU - Yokode, Masayuki
AU - Minami, Manabu
N1 - Funding Information:
Supported in part by Japan Society for the Promotion of Science grants 23590361 and 26460338 (M.M.), 15K08230 (M.Y.), and 820140600019 (R.F.).
Publisher Copyright:
© 2017 American Society for Investigative Pathology
PY - 2017/8
Y1 - 2017/8
N2 - Microglia are thought to play key roles in the progression of Alzheimer disease (AD). Overactivated microglia produce proinflammatory cytokines, such as tumor necrosis factor-α, which appear to contribute to disease progression. Previously, we reported that prostaglandin E2 type 4 receptor–associated protein (EPRAP) promotes microglial activation. We crossed human amyloid precursor protein transgenic mice from strain J20+/− onto an EPRAP-deficient background to determine the role of EPRAP in AD. Behavioral tests were performed in 5-month-old male J20+/−EPRAP+/+ and J20+/−EPRAP−/− mice. EPRAP deficiency reversed the reduced anxiety of J20+/− mice but did not affect hyperactivity. No differences in spatial memory were observed between J20+/−EPRAP+/+ and J20+/−EPRAP−/− mice. In comparison with J20+/−EPRAP+/+, J20+/−EPRAP−/− mice exhibited less microglial accumulation and reductions in the Cd68 and tumor necrosis factor-α mRNAs in the prefrontal cortex and hippocampus. No significant differences were found between the two types of mice in the amount of amyloid-β 40 or 42 in the cortex and hippocampus. J20+/−EPRAP−/− mice reversed the reduced anxiety-like behavior and had reduced microglial activation compared with J20+/−EPRAP+/+ mice. Further research is required to identify the role of EPRAP in AD, but our results indicate that EPRAP may be related to behavioral and psychological symptoms of dementia and inflammation in patients with AD.
AB - Microglia are thought to play key roles in the progression of Alzheimer disease (AD). Overactivated microglia produce proinflammatory cytokines, such as tumor necrosis factor-α, which appear to contribute to disease progression. Previously, we reported that prostaglandin E2 type 4 receptor–associated protein (EPRAP) promotes microglial activation. We crossed human amyloid precursor protein transgenic mice from strain J20+/− onto an EPRAP-deficient background to determine the role of EPRAP in AD. Behavioral tests were performed in 5-month-old male J20+/−EPRAP+/+ and J20+/−EPRAP−/− mice. EPRAP deficiency reversed the reduced anxiety of J20+/− mice but did not affect hyperactivity. No differences in spatial memory were observed between J20+/−EPRAP+/+ and J20+/−EPRAP−/− mice. In comparison with J20+/−EPRAP+/+, J20+/−EPRAP−/− mice exhibited less microglial accumulation and reductions in the Cd68 and tumor necrosis factor-α mRNAs in the prefrontal cortex and hippocampus. No significant differences were found between the two types of mice in the amount of amyloid-β 40 or 42 in the cortex and hippocampus. J20+/−EPRAP−/− mice reversed the reduced anxiety-like behavior and had reduced microglial activation compared with J20+/−EPRAP+/+ mice. Further research is required to identify the role of EPRAP in AD, but our results indicate that EPRAP may be related to behavioral and psychological symptoms of dementia and inflammation in patients with AD.
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U2 - 10.1016/j.ajpath.2017.04.010
DO - 10.1016/j.ajpath.2017.04.010
M3 - Article
C2 - 28624505
AN - SCOPUS:85023601588
VL - 187
SP - 1848
EP - 1854
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 8
ER -