Upregulation of cholinergic modulators Lypd6 and Lypd6b associated with autism drives anxiety and cognitive decline.

Autor: Isaev AB; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.; Moscow Center for Advanced Studies, Moscow, Russia., Bychkov ML; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia., Kulbatskii DS; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia., Andreev-Andrievskiy AA; Interdisciplinary Scientific and Educational School of Moscow University «Molecular Technologies of the Living Systems and Synthetic Biology», Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia.; Institute for Biomedical Problems of Russian Academy of Sciences, Moscow, Russia., Mashkin MA; Institute for Biomedical Problems of Russian Academy of Sciences, Moscow, Russia., Shulepko MA; Shenzhen MSU-BIT University, Shenzhen, China., Shlepova OV; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.; Moscow Center for Advanced Studies, Moscow, Russia., Loktyushov EV; Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, Institute for Biological Instrumentation, Pushchino, Russia., Latanov AV; Interdisciplinary Scientific and Educational School of Moscow University «Molecular Technologies of the Living Systems and Synthetic Biology», Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia., Kirpichnikov MP; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.; Interdisciplinary Scientific and Educational School of Moscow University «Molecular Technologies of the Living Systems and Synthetic Biology», Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia., Lyukmanova EN; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia. lyukmanova_ekaterina@smbu.edu.cn.; Moscow Center for Advanced Studies, Moscow, Russia. lyukmanova_ekaterina@smbu.edu.cn.; Interdisciplinary Scientific and Educational School of Moscow University «Molecular Technologies of the Living Systems and Synthetic Biology», Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia. lyukmanova_ekaterina@smbu.edu.cn.; Shenzhen MSU-BIT University, Shenzhen, China. lyukmanova_ekaterina@smbu.edu.cn.
Jazyk: angličtina
Zdroj: Cell death discovery [Cell Death Discov] 2024 Oct 21; Vol. 10 (1), pp. 444. Date of Electronic Publication: 2024 Oct 21.
DOI: 10.1038/s41420-024-02211-z
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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