5-HT1A R alleviates Aβ-induced cognitive decline and neuroinflammation through crosstalk with NF-κB pathway in mice

International Immunopharmacology
Meng WangYi-Hua Qian

Abstract

The 5-hydroxytryptamine (5-HT) receptor is significant for the regulation of mood and memory. However, the role of 5-HT1AR in β-Amyloid protein (Aβ)-induced cognitive decline, neuroinflammation and the possible mechanism remains elusive. Thus, we aimed to evaluate the effects of 5-HT1AR on Aβ-induced learning and memory decline and neuroinflammation in mice. Novel object recognition and Morris water maze tests were performed to observe learning and memory behavior in mice. Protein levels of Iba1, GFAP, MAP2, TNF-α, Tβ4, C-fos, IKK-β, IKB-α, NF-κBp65, phospho-NF-κBp65 in the hippocampus were examined by immunostaining or western blotting. Aβ1-42-treatment inducing learning and memory decline was shown in novel object recognition and Morris water maze tests; neuroinflammation shown in immunostaining. Our study found out that 5-HT1AR inhibitor WAY100635 showed significant improvement in Aβ-induced learning and memory decline. Moreover, WAY100635 decreases levels of Iba1, GFAP, and TNF-α in the hippocampus, which were related to neuroinflammation. While treatment with 5-HT1AR agonist 8-OH-DPAT or ERK inhibitor U0126 exerted no effects or even aggravated Aβ-induced learning and memory decline. In addition, WAY100635 could downregula...Continue Reading

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