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

Deficiency in EP4 Receptor-Associated Protein Ameliorates Abnormal Anxiety-Like Behavior and Brain Inflammation in a Mouse Model of Alzheimer Disease. Am J Pathol. 2017 Jun 15;: Authors: Fujikawa R, Higuchi S, Nakatsuji M, Yasui M, Ikedo T, Nagata M, Hayashi K, Yokode M, Minami M 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(-/-) mi...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research