NRBF2 plays a crucial role in the acquisition process of learning and memory, independent of the Vps34 complex

IntroductionNRBF2, a component of autophagy-associated PIK3C3/VPS34-containing phosphatidylinositol 3-kinase complex, plays a crucial role in learning and memory processes, yet its specific impact on memory and the underlying molecular mechanisms remains unclear.MethodsHere, we utilized NRBF2 knocko...

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Main Authors: Songfen Wu, Haicai Zhuang, Xidan Zhou, Kuan Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Behavioral Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fnbeh.2025.1529522/full
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author Songfen Wu
Songfen Wu
Songfen Wu
Haicai Zhuang
Haicai Zhuang
Haicai Zhuang
Xidan Zhou
Kuan Li
Kuan Li
Kuan Li
author_facet Songfen Wu
Songfen Wu
Songfen Wu
Haicai Zhuang
Haicai Zhuang
Haicai Zhuang
Xidan Zhou
Kuan Li
Kuan Li
Kuan Li
author_sort Songfen Wu
collection DOAJ
description IntroductionNRBF2, a component of autophagy-associated PIK3C3/VPS34-containing phosphatidylinositol 3-kinase complex, plays a crucial role in learning and memory processes, yet its specific impact on memory and the underlying molecular mechanisms remains unclear.MethodsHere, we utilized NRBF2 knockout mice to examine its influence on the time course of fear memory. Employing quantitative PCR, Western blot analysis, behavioral tests, and electrophysiology, we investigated the mechanisms through which NRBF2 affects memory processing.ResultsWe observed an increase in Nrbf2 mRNA levels at 6 and 12 h, and protein levels at 6 h post fear conditioning. Depletion of NRBF2 impaired memory acquisition, short-term, and long-term memory without causing any anxiety-like behavior. Interestingly, inhibition of Vps34 and autophagy by SAR405 disrupted fear memory consolidation, while leaving memory acquisition, short-term memory, and long-term potentiation (LTP) unaffected. Our results suggested that NRBF2 deletion impaired memory acquisition through an autophagy-independent pathway and provided novel insights into the role of NRBF2 in the central nervous system.DiscussionThis study offer new insights into the role of NRBF2 and highlight the potential of targeting NRBF2 as a therapeutic strategy for addressing cognitive deficits associated with various disorders.
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spelling doaj-art-6882505e94894ab195e5d3b77dafdb0c2025-02-12T07:26:06ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532025-02-011910.3389/fnbeh.2025.15295221529522NRBF2 plays a crucial role in the acquisition process of learning and memory, independent of the Vps34 complexSongfen Wu0Songfen Wu1Songfen Wu2Haicai Zhuang3Haicai Zhuang4Haicai Zhuang5Xidan Zhou6Kuan Li7Kuan Li8Kuan Li9School of Pharmacy, Guangdong Medical University, Zhanjiang, ChinaDepartment of Pharmacy, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, Guangzhou, ChinaThe First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, ChinaSchool of Pharmacy, Guangdong Medical University, Zhanjiang, ChinaDepartment of Pharmacy, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, Guangzhou, ChinaThe First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, ChinaThe Brain Cognition and Brain Disease Institute, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaSchool of Pharmacy, Guangdong Medical University, Zhanjiang, ChinaDepartment of Pharmacy, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, Guangzhou, ChinaThe First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, ChinaIntroductionNRBF2, a component of autophagy-associated PIK3C3/VPS34-containing phosphatidylinositol 3-kinase complex, plays a crucial role in learning and memory processes, yet its specific impact on memory and the underlying molecular mechanisms remains unclear.MethodsHere, we utilized NRBF2 knockout mice to examine its influence on the time course of fear memory. Employing quantitative PCR, Western blot analysis, behavioral tests, and electrophysiology, we investigated the mechanisms through which NRBF2 affects memory processing.ResultsWe observed an increase in Nrbf2 mRNA levels at 6 and 12 h, and protein levels at 6 h post fear conditioning. Depletion of NRBF2 impaired memory acquisition, short-term, and long-term memory without causing any anxiety-like behavior. Interestingly, inhibition of Vps34 and autophagy by SAR405 disrupted fear memory consolidation, while leaving memory acquisition, short-term memory, and long-term potentiation (LTP) unaffected. Our results suggested that NRBF2 deletion impaired memory acquisition through an autophagy-independent pathway and provided novel insights into the role of NRBF2 in the central nervous system.DiscussionThis study offer new insights into the role of NRBF2 and highlight the potential of targeting NRBF2 as a therapeutic strategy for addressing cognitive deficits associated with various disorders.https://www.frontiersin.org/articles/10.3389/fnbeh.2025.1529522/fullNrbf2VPS34autophagymemory acquisitionLTP
spellingShingle Songfen Wu
Songfen Wu
Songfen Wu
Haicai Zhuang
Haicai Zhuang
Haicai Zhuang
Xidan Zhou
Kuan Li
Kuan Li
Kuan Li
NRBF2 plays a crucial role in the acquisition process of learning and memory, independent of the Vps34 complex
Frontiers in Behavioral Neuroscience
Nrbf2
VPS34
autophagy
memory acquisition
LTP
title NRBF2 plays a crucial role in the acquisition process of learning and memory, independent of the Vps34 complex
title_full NRBF2 plays a crucial role in the acquisition process of learning and memory, independent of the Vps34 complex
title_fullStr NRBF2 plays a crucial role in the acquisition process of learning and memory, independent of the Vps34 complex
title_full_unstemmed NRBF2 plays a crucial role in the acquisition process of learning and memory, independent of the Vps34 complex
title_short NRBF2 plays a crucial role in the acquisition process of learning and memory, independent of the Vps34 complex
title_sort nrbf2 plays a crucial role in the acquisition process of learning and memory independent of the vps34 complex
topic Nrbf2
VPS34
autophagy
memory acquisition
LTP
url https://www.frontiersin.org/articles/10.3389/fnbeh.2025.1529522/full
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