Isaev Aizek B, Bychkov Maxim L, Kulbatskii Dmitrii S, Andreev-Andrievskiy Alexander A, Mashkin Mikhail A, Shulepko Mikhail A, Shlepova Olga V, Loktyushov Eugene V, Latanov Alexander V, Kirpichnikov Mikhail P, Lyukmanova Ekaterina N
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
Moscow Center for Advanced Studies, Moscow, Russia.
Cell Death Discov. 2024 Oct 21;10(1):444. doi: 10.1038/s41420-024-02211-z.
Intellectual disability and autistic features are associated with chromosome region 2q23.q23.2 duplication carrying LYPD6 and LYPD6B genes. Here, we analyzed LYPD6 and LYPD6B expression in patients with different neuropsychiatric disorders. Increased LYPD6 and LYPD6B expression was revealed in autism and other disorders. To study possible consequences of Lypd6 and Lypd6b overexpression in the brain, we used a mouse model with intracerebroventricular delivery of recombinant analogs of these proteins. A two-week infusion evoked significant memory impairment and acute stress. Both modulators downregulated hippocampal and amygdala dendritic spine density. No changes in synaptic plasticity were observed. Intracerebroventricular administration by both proteins downregulated hippocampal expression of Lypd6, Lypd6b, and α7 nicotinic acetylcholine receptor (nAChR). Similar to Lypd6, Lypd6b targeted different nAChR subtypes in the brain with preferential inhibition of α7- and α4β2-nAChRs. Thus, increased Lypd6 and Lypd6b level in the brain are linked to cholinergic system depression, neuronal atrophy, memory decline, and anxiety.
智力残疾和自闭症特征与携带LYPD6和LYPD6B基因的2q23.q23.2染色体区域重复有关。在此，我们分析了不同神经精神疾病患者中LYPD6和LYPD6B的表达情况。在自闭症和其他疾病中发现LYPD6和LYPD6B表达增加。为了研究Lypd6和Lypd6b在大脑中过表达的可能后果，我们使用了一种通过脑室内注射这些蛋白质重组类似物的小鼠模型。为期两周的输注引发了显著的记忆障碍和急性应激。两种调节剂均下调了海马体和杏仁核的树突棘密度。未观察到突触可塑性的变化。两种蛋白质经脑室内给药均下调了海马体中Lypd
