Amyloid β 1–42 peptide (Aβ_1–42) accumulates in Alzheimer's disease (AD) that is toxic to the basal forebrain cholinergic (BFC) neurons in substantia innominata-nucleus basalis magnocellularis complex (SI-NBM). Transient Receptor Potential Ankyrin1 (TRPA1) receptor is present in murine brain, however its role in neurotoxic processes is unclear. We investigated the Aβ_1–42-induced neurotoxicity in TRPA1 wild-type (TRPA1^+/+) and knockout (TRPA1^−/−) mice.

Expression and neuroanatomical localization of TRPA1 receptor were examined using RT qPCR. Cholinergic fibre loss was determined on acetylcholinesterase (AChE) stained brain slices, and choline acetyltransferase (ChAT) immunohistochemistry was used to assess the cholinergic cell loss. Novel object recognition (NOR), radial arm maze (RAM) and Y-maze tests were used to investigate memory loss.

Aβ_1–42-injected WT mice showed marked loss of cholinergic fibres and cell bodies, which was significantly attenuated in TRPA1^−/− animals. According to the NOR and RAM tests, pronounced memory loss was detected in Aβ_1–42-injected TRPA1^+/+ mice, but not in TRPA1^−/− group.

Our findings demonstrate that TRPA1 KO animals show substantially reduced morphological damage and memory loss after Aβ_1–42 injection in the SI-NBM. We conclude that TRPA1 receptors may play an important deteriorating role in the Aβ_1–42-induced cholinergic neurotoxicity and the consequent memory loss in the murine brain.

淀粉样蛋白β1–42肽（_Aβ1–42）在阿尔茨海默氏病（AD）中积累，该疾病对无名状实核-基底性大细胞复合物（SI-NBM）中的基底前脑胆碱能（BFC）神经元具有毒性。鼠脑中存在瞬态受体潜在的锚蛋白（TRPA1）受体，但是尚不清楚其在神经毒性过程中的作用。我们研究了_Aβ1–42诱导的TRPA1野生型（TRPA1 ^{+ / +}）和基因敲除（TRPA1 ^-/-）小鼠的神经毒性。

使用RT qPCR检查TRPA1受体的表达和神经解剖定位。在乙酰胆碱酯酶（AChE）染色的脑切片上测定胆碱能纤维的损失，并用胆碱乙酰转移酶（ChAT）免疫组织化学评估胆碱能细胞的损失。新型对象识别（NOR），radial臂迷宫（RAM）和Y迷宫测试用于研究记忆丧失。

Aβ _1-42 -injected野生型小鼠表现出胆碱能纤维和细胞体，这是TRPA1减弱显著的很大损失^{- / -}动物。根据NOR和RAM测试，在注射_Aβ1–42的TRPA1 ^{+ / +}小鼠中检测到明显的记忆力丧失，但在TRPA1 ^-/-组中未检测到。

我们的发现表明，在SI-NBM中注射_Aβ1–42后，TRPA1 KO动物的形态学损伤和记忆力丧失显着降低。我们得出的结论是，TRPA1受体可能在_Aβ1–42诱导的胆碱能神经毒性和鼠脑的记忆丧失中起重要的恶化作用。