ArticleCerebral cortex (New York, N.Y. : 1991)2021
Reversal of Age-Related Neuronal Atrophy by α5-GABAA Receptor Positive Allosteric Modulation.
Article in Cerebral cortex (New York, N.Y. : 1991), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- The role of GABANeuroscience and biobehavioral reviews · 2026Review
- A Comparison of Positive and Negative Allosteric Modulators of α5-Containing GABABiological psychiatry · 2026Review
- Behavioral Domain-Specific Effects of Positive Modulation of α5 and α6 GABAPharmacology research & perspectives · 2026Article
- A Novel Polygenic Risk Score Indexing Somatostatin-Expressing Inhibitory Neurons Predicts Somatostatin-Expressing Cell Proportions and Severity of Symptoms in Late-Life Depression.Biological psychiatry global open science · 2026Article
- Linking Age Changes in Human Cortical Microcircuits to Impaired Brain Function and EEG Biomarkers.Aging cell · 2026Article
- Intranasal Insulin Mitigates Memory Impairment and Neuroinflammation in a Mouse Model of Hippocampal Aging.Pharmacology research & perspectives · 2025Article
- Age-dependent increases in dorsal hippocampal postsynaptic α5GABA-a receptors may be lost in a rat model of Alzheimer's disease.Scientific reports · 2025Article
- Noncanonical sustained actions of propofol reverse surgery-induced microglial activation and cognitive impairment in aged mice.PNAS nexus · 2025Article
- Chronic α5-GABA-A Receptor Potentiation Promotes Mouse Adult Hippocampal Neurogenesis.Hippocampus · 2025Article
- Spine loss in depression impairs dendritic signal integration in human cortical microcircuit models.iScience · 2025Article
- Parenteral Nanoemulsion for Optimized Delivery of GL-II-73 to the Brain-Comparative In Vitro Blood-Brain Barrier and In Vivo Neuropharmacokinetic Evaluation.Pharmaceutics · 2025Article
- Therapeutic dose prediction of α5-GABA receptor modulation from simulated EEG of depression severity.PLoS computational biology · 2024Article
- In-silico testing of new pharmacology for restoring inhibition and human cortical function in depression.Communications biology · 2024Article
- GABATrends in pharmacological sciences · 2023Review
- GL-II-73, a Positive Allosteric Modulator of α5GABAInternational journal of molecular sciences · 2023Article
- Synthesis and Receptor Binding Studies of α5 GABAMolecules (Basel, Switzerland) · 2023Article
- Overexpression of Parkin in the Neuronal Progenitor Cells from a Patient with Parkinson's Disease Shifts the Transcriptome Towards the Normal State.Molecular neurobiology · 2023Article
- Aberrant Dopamine System Function in the Ferrous Amyloid Buthionine (FAB) Rat Model of Alzheimer's Disease.International journal of molecular sciences · 2023Article
- Neurotrophic effects of potentiating gaba-mediated dendritic inhibition.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Brain structure and working memory adaptations associated with maturation and aging in mice.Frontiers in aging neuroscience · 2023Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Aging is associated with reduced brain volume, altered neural activity, and neuronal atrophy in cortical-like structures, comprising the frontal cortex and hippocampus, together contributing to cognitive impairments. Therapeutic efforts aimed at reversing these deficits have focused on excitatory or neurotrophic mechanisms, although recent findings show that reduced dendritic inhibition mediated by α5-subunit containing GABA-A receptors (α5-GABAA-Rs) occurs during aging and contributes to cognitive impairment. Here, we aimed to confirm the beneficial effect on working memory of augmenting α5-GABAA-R activity in old mice and tested its potential at reversing age-related neuronal atrophy. We show that GL-II-73, a novel ligand with positive allosteric modulatory activity at α5-GABAA-R (α5-PAM), increases dendritic branching complexity and spine numbers of cortical neurons in vitro. Using old mice, we confirm that α5-PAM reverses age-related working memory deficits and show that chronic treatment (3 months) significantly reverses age-related dendritic shrinkage and spine loss in frontal cortex and hippocampus. A subsequent 1-week treatment cessation (separate cohort) resulted in loss of efficacy on working memory but maintained morphological neurotrophic effects. Together, the results demonstrate the beneficial effect on working memory and neurotrophic efficacy of augmenting α5-GABAA-R function in old mice, suggesting symptomatic and disease-modifying potential in age-related brain disorders.
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Registered trials
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.