Evidence map›Paper›PMID 39012419›Full record

ArticlePharmacological reports : PR2024

Enhanced hippocampal TIAM2S expression alleviates cognitive deficits in Alzheimer's disease model mice.

Kuan-Chin Sung, Li-Yun Wang, Che-Chuan Wang, Chun-Hsien Chu, H Sunny Sun, Ya-Hsin Hsiao

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Article in Pharmacological reports : PR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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6 authors.

Kuan-Chin Sung *Department of Neurosurgery, Chi-Mei Medical Center, 901 Chung Hwa Road, Yung Kang City, Tainan, Taiwan.
Li-Yun Wang *Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan.
Che-Chuan WangDepartment of Neurosurgery, Chi-Mei Medical Center, 901 Chung Hwa Road, Yung Kang City, Tainan, Taiwan.
Chun-Hsien ChuInstitute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
H Sunny SunInstitute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Ya-Hsin HsiaoDepartment of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan. yahsin@mail.ncku.edu.tw.ORCID http://orcid.org/0000-0003-2885-3905

Funding

Ministry of Science and Technology, Taiwan MOST 110-2628-B-006-035Ministry of Science and Technology, Taiwan MOST 111-2628-B-006-002-Ministry of Science and Technology, Taiwan NSTC 112-2320-B-006 -030 -MY3
6 · The paper itself

Abstract

backgroundDendritic spine dysfunction is a key feature of Alzheimer's disease (AD) pathogenesis. Human T-cell lymphoma invasion and metastasis 2 (TIAM2) is expressed in two isoforms, the full length (TIAM2L) and a short transcript (TIAM2S). Compared to TIAM2L protein, which is undetectable, TIAM2S protein is abundant in human brain tissue, especially the hippocampus, and can promote neurite outgrowth in our previous findings. However, whether enhanced hippocampal TIAM2S expression can alleviate cognitive deficits in Alzheimer's disease model mice remains unclear.

methodsWe crossbred 3xTg-AD with TIAM2S mice to generate an AD mouse model that carries the human TIAM2S gene (3xTg-AD/TIAM2S mice). The Morris water maze and object location tests assessed hippocampus-dependent spatial memory. Lentiviral-driven shRNA or cDNA approaches were used to manipulate hippocampal TIAM2S expression. Golgi staining and Sholl analysis were utilized to measure neuronal dendrites and dendritic spines in the mouse hippocampi.

resultsCompared to 3xTg-AD mice, 3xTg-AD/TIAM2S mice displayed improved cognitive functions. According to the hippocampus is one of the earliest affected brain regions by AD, we further injected TIAM2S shRNA or TIAM2S cDNA into mouse hippocampi to confirm whether manipulating hippocampal TIAM2S expression could affect AD-related cognitive functions. The results showed that the reduced hippocampal TIAM2S expression in 3xTg-AD/TIAM2S mice abolished the memory improvement effect, whereas increased hippocampal TIAM2S levels alleviated cognitive deficits in 3xTg-AD mice. Furthermore, we found that TIAM2S-mediated memory improvement was achieved by regulating dendritic plasticity.

conclusionsThese results will provide new insights into connecting TIAM2S with AD and support the notion that TIAM2S should be investigated as potential AD therapeutic targets.

Indexed as

Alzheimer DiseaseCognitive DysfunctionDisease Models, AnimalHippocampusMice, TransgenicAnimalsDendritic SpinesGuanine Nucleotide Exchange FactorsHumansMaleMaze LearningMiceSpatial MemoryGuanine Nucleotide Exchange FactorsAlzheimer’s diseaseCognitive deficitsDendritic plasticityHippocampusTIAM2S

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.