Crucial role of Snf7-3 in synaptic function and cognitive behavior revealed by conventional and conditional knockout mouse models.

Autor: Kim H; School of Biological Sciences, Seoul National University, Seoul 08826, South Korea., Jang JW; Department of Biological Sciences and Biotechnology, College of Life Sciences and Nanotechnology, Hannam University, Daejeon, Korea., Sim SE; School of Biological Sciences, Seoul National University, Seoul 08826, South Korea., Lee J; School of Biological Sciences, Seoul National University, Seoul 08826, South Korea., Jeong JH; School of Biological Sciences, Seoul National University, Seoul 08826, South Korea., Park S; Department of Biological Sciences and Biotechnology, College of Life Sciences and Nanotechnology, Hannam University, Daejeon, Korea., Lee YK; Department of Biological Sciences and Biotechnology, College of Life Sciences and Nanotechnology, Hannam University, Daejeon, Korea., Ham HJ; Department of Biological Sciences and Biotechnology, College of Life Sciences and Nanotechnology, Hannam University, Daejeon, Korea., Yu NK; School of Biological Sciences, Seoul National University, Seoul 08826, South Korea., Lim CS; Department of Pharmacology, Wonkwang University School of Medicine, Jeonbuk 54538, South Korea., Gao FB; RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, USA., Lee JA; Department of Biological Sciences and Biotechnology, College of Life Sciences and Nanotechnology, Hannam University, Daejeon, Korea. Electronic address: leeja@hnu.kr., Kaang BK; School of Biological Sciences, Seoul National University, Seoul 08826, South Korea; Center for Cognition and Sociality, Life Science Institute, Institute for Basic Science (IBS), Daejeon 34141, South Korea. Electronic address: kaang@ibs.re.kr.
Jazyk: angličtina
Zdroj: Neuroscience [Neuroscience] 2024 Nov 12; Vol. 560, pp. 347-356. Date of Electronic Publication: 2024 Oct 05.
DOI: 10.1016/j.neuroscience.2024.10.010
Abstrakt: Snf7-3 is a crucial component of the endosomal sorting complexes required for transport (ESCRT) pathway, playing a vital role in endolysosomal functions. To elucidate the role of Snf7-3 in vivo, we developed conventional-like and conditional Snf7-3 knockout (KO) mouse models using a "Knockout-first" strategy. Conventional-like Snf7-3 KO mice showed significantly reduced Snf7-3 mRNA expression, and older mice (25-40 weeks) exhibited impaired social recognition and increased miniature excitatory postsynaptic currents (mEPSCs). Similarly, conditional KO mice aged 8-24 weeks, with Snf7-3 specifically deleted in forebrain excitatory neurons, displayed impaired object location memory and elevated mEPSC frequency. Consistently, Snf7-3 knockdown in cultured mouse hippocampal neurons led to increased densities of pre- and postsynaptic puncta, supporting the observed increase in mEPSC frequency. In addition, enhanced dendritic complexity was observed in the medial prefrontal cortex of these mice, indicating early synaptic disturbances. Our findings underscore the critical role of Snf7-3 in maintaining normal cognitive functions and social behaviors. The observed synaptic and behavioral deficits in both conventional-like and conditional KO mice highlight the importance of Snf7-3 in specific neuronal populations, suggesting that early synaptic changes could precede more pronounced cognitive impairments.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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