ArticleMolecular therapy : the journal of the American Society of Gene Therapy2017
Correcting miR92a-vGAT-Mediated GABAergic Dysfunctions Rescues Human Tau-Induced Anxiety in Mice.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- The GABAergic system in Alzheimer's disease: a systematic review with meta-analysis.Molecular psychiatry · 2023Pooled it
- Ursolic acid reduces Aβ-driven aggression via Gab1-mediated autophagy and dorsal hippocampal circuit modulation in Alzheimer's disease.Journal of advanced research · 2026Article
- Advances in Alzheimer's disease: mechanistic insights and therapeutic targets.Science China. Life sciences · 2026Review
- MicroRNA-148a regulates depressive-like behaviors in mice via the Otx2/Dopaminergic signaling axis.Molecular psychiatry · 2026Article
- The emerging role of miRNAs in biological aging and age-related diseases.Non-coding RNA research · 2025Review
- Accumulation of GSK-3β in Interneurons Impairs Adult Hippocampal Neurogenesis by Inhibiting GABAergic Transmission.Aging cell · 2025Article
- Genomic ncRNAs regulating mitochondrial function in neurodegeneration: a neglected clue in the complex etiopathogenesis of multiple sclerosis.Cell & bioscience · 2025Article
- Kv1.1 channel dysfunction in parvalbumin-positive interneurons contributes to anxiety-like behaviors in young adult presenilin 1/2 conditional double knockout mice.Cell & bioscience · 2025Article
- Therapeutic potential and microRNA regulating properties of phytochemicals in Alzheimer's disease.Molecular therapy. Nucleic acids · 2025Review
- Mitochondrial microRNAs: Key Drivers in Unraveling Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- miR-423-5p and miR-92a-3p in Alzheimer's disease: relationship with pathology and cognition.Frontiers in aging neuroscience · 2025Article
- Blood-derived microRNAs are related to cognitive domains in the general population.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Profiling Small RNA From Brain Extracellular Vesicles in Individuals With Depression.The international journal of neuropsychopharmacology · 2024Article
- MicroRNA biomarkers as next-generation diagnostic tools for neurodegenerative diseases: a comprehensive review.Frontiers in molecular neuroscience · 2024Review
- Longitudinal faster anxiety progression ofFrontiers in neuroscience · 2024Article
- The role of epigenetics in anxiety disorders.Molecular biology reports · 2023Review
- MAPK Is a Mutual Pathway Targeted by Anxiety-Related miRNAs, and E2F5 Is a Putative Target for Anxiolytic miRNAs.Biomolecules · 2023Article
- TMEM16F may be a new therapeutic target for Alzheimer's disease.Neural regeneration research · 2023Article
- Review
- Identification of miRNAs regulating MAPT expression and their analysis in plasma of patients with dementia.Frontiers in molecular neuroscience · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patients with Alzheimer's disease (AD) commonly show anxiety behaviors, but the molecular mechanisms are not clear and no efficient intervention exists. Here, we found that overexpression of human wild-type, full-length tau (termed htau) in hippocampus significantly decreased the extracellular γ-aminobutyric acid (GABA) level with inhibition of γ oscillation and the evoked inhibitory postsynaptic potential (eIPSP). With tau accumulation, the mice show age-dependent anxiety behaviors. Among the factors responsible for GABA synthesis, release, uptake, and transport, we found that accumulation of htau selectively suppressed expression of the intracellular vesicular GABA transporter (vGAT). Tau accumulation increased miR92a, which targeted vGAT mRNA 3' UTR and inhibited vGAT translation. Importantly, we found that upregulating GABA tones by intraperitoneal injection of midazolam (a GABA agonist), ChR2-mediated photostimulating and overexpressing vGAT, or blocking miR92a by using specific antagomir or inhibitor efficiently rescued the htau-induced GABAergic dysfunctions with attenuation of anxiety. Finally, we also demonstrated that vGAT level decreased while the miR92a increased in the AD brains. These findings demonstrate that the AD-like tau accumulation induces anxiety through disrupting miR92a-vGAT-GABA signaling, which reveals molecular mechanisms underlying the anxiety behavior in AD patients and potentially leads to the development of new therapeutics for tauopathies.
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