Deficiency in EP4 Receptor–Associated Protein Ameliorates Abnormal Anxiety-Like Behavior and Brain Inflammation in a Mouse Model of Alzheimer Disease

Risako Fujikawa, Sei Higuchi, Masato Nakatsuji, Mika Yasui, Taichi Ikedo, Manabu Nagata, Kosuke Hayashi, Masayuki Yokode, Manabu Minami

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)1848-1854
Number of pages7
JournalAmerican Journal of Pathology
Volume187
Issue number8
DOIs
Publication statusPublished - Aug 2017

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Encephalitis
Alzheimer Disease
Anxiety
Proteins
Microglia
Hippocampus
Tumor Necrosis Factor-alpha
Protein Deficiency
Behavioral Symptoms
Amyloid beta-Protein Precursor
Prefrontal Cortex
Dinoprostone
Amyloid
Transgenic Mice
Dementia
Disease Progression
Cytokines
Psychology

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Deficiency in EP4 Receptor–Associated Protein Ameliorates Abnormal Anxiety-Like Behavior and Brain Inflammation in a Mouse Model of Alzheimer Disease. / Fujikawa, Risako; Higuchi, Sei; Nakatsuji, Masato; Yasui, Mika; Ikedo, Taichi; Nagata, Manabu; Hayashi, Kosuke; Yokode, Masayuki; Minami, Manabu.

In: American Journal of Pathology, Vol. 187, No. 8, 08.2017, p. 1848-1854.

Research output: Contribution to journalArticle

Fujikawa, Risako ; Higuchi, Sei ; Nakatsuji, Masato ; Yasui, Mika ; Ikedo, Taichi ; Nagata, Manabu ; Hayashi, Kosuke ; Yokode, Masayuki ; Minami, Manabu. / Deficiency in EP4 Receptor–Associated Protein Ameliorates Abnormal Anxiety-Like Behavior and Brain Inflammation in a Mouse Model of Alzheimer Disease. In: American Journal of Pathology. 2017 ; Vol. 187, No. 8. pp. 1848-1854.
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