[Mitochondrial calcium uniporter knockdown in hippocampal neurons improved the learning and memory dysfunction of Alzheimer's disease mice].

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder, which seriously affects health of the elderly, and is still irreversible up to now. Recent studies have indicated that mitochondrial dysfunction is a direct reason to promote the development of AD. Mitochondrial calcium uniporter (MCU), located in the inner membrane of mitochondria, is a key channel of mitochondrial Ca2+ uptake. Abnormal MCU expression results in imbalance of mitochondrial calcium homeostasis, ultimately leading to mitochondrial dysfunction. The purpose of this study was to determine the effects of MCU knockdown on AD hippocampal neurons and learning and memory function of AD model mice. Lentivirus and adeno-associated virus were used as vectors to transfect shRNA into hippocampal neurons (HT22 cells) and hippocampi of amyloid precursor protein (APP)/presenilin 1 (PS1)/tau AD transgenic mice, respectively, in order to interfere with MCU expression. The cellular activity of HT22 cells was detected by MTS method, and the changes of learning and memory dysfunction in APP/PS1/tau AD transgenic mice were tested by Y maze and Morris water maze. The results showed that MCU knockdown reversed the cellular activity of HT22 cells decreased by amyloid beta protein 1-42 (Aβ1-42) or okadaic acid (OA). Knockdown of MCU in hippocampal neurons improved spontaneous alternation (spatial working memory), decreased escape latency, and increased time in target quadrant and number of platform crossing (spatial reference memory) of the APP/PS1/tau mice. This study suggests that MCU knockdown in hippocampal neurons has anti-AD effect, and it is expected to be a new strategy for prevention and treatment of AD.

• Authors: Hong-Yan Cai, Jing Qiao, Si-Ru Chen, Wei-Ping Fan
• Journal: Sheng li xue bao : [Acta physiologica Sinica] (Sheng Li Xue Bao) Vol. 74 Issue 5 Pg. 715-725 (Oct 25 2022) ISSN: 0371-0874 [Print] China
• PMID: 36319095 (Publication Type: English Abstract, Journal Article)

Chemical References

• Amyloid beta-Peptides
• mitochondrial calcium uniporter
• Amyloid beta-Protein Precursor

Topics

• Animals
• Mice
• Alzheimer Disease
• Amyloid beta-Peptides (metabolism)
• Disease Models, Animal
• Hippocampus (metabolism)
• Amyloid beta-Protein Precursor (metabolism)
• Neurons
• Mice, Transgenic