Mossy cell synaptic dysfunction causes memory imprecision via miR-128 inhibition of STIM2 in Alzheimer's disease mouse model.
Manfei DengQingping ZhangZhuoze WuTian MaAodi HeTongmei ZhangXiao KeQuntao YuYunyun HanYouming LuPublished in: Aging cell (2020)
Recently, we have reported that dentate mossy cells (MCs) control memory precision via directly and functionally innervating local somatostatin (SST) inhibitory interneurons. Here, we report a discovery that dysfunction of synaptic transmission between MCs and SST cells causes memory imprecision in a mouse model of early Alzheimer's disease (AD). Single-cell RNA sequencing reveals that miR-128 that binds to a 3'UTR of STIM2 and inhibits STIM2 translation is increasingly expressed in MCs from AD mice. Silencing miR-128 or disrupting miR-128 binding to STIM2 evokes STIM2 expression, restores synaptic function, and rescues memory imprecision in AD mice. Comparable findings are achieved by directly engineering MCs with the expression of STIM2. This study unveils a key synaptic and molecular mechanism that dictates how memory maintains or losses its details and warrants a promising target for therapeutic intervention of memory decays in the early stage of AD.
Keyphrases
- single cell
- mouse model
- cell proliferation
- long non coding rna
- working memory
- poor prognosis
- early stage
- long noncoding rna
- induced apoptosis
- high throughput
- randomized controlled trial
- rna seq
- cognitive decline
- oxidative stress
- cell cycle arrest
- small molecule
- type diabetes
- squamous cell carcinoma
- prefrontal cortex
- metabolic syndrome
- high fat diet induced
- cell therapy
- binding protein
- cell death
- neoadjuvant chemotherapy
- endoplasmic reticulum stress
- mild cognitive impairment
- wild type