ArticleMolecular neurodegeneration2017
Gad67 haploinsufficiency reduces amyloid pathology and rescues olfactory memory deficits in a mouse model of Alzheimer's disease.
Article in Molecular neurodegeneration, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 57 citations in OpenAlex.
- Characterization of motor and non-motor features associated with bilateral nigral degeneration due to A53T alpha-synuclein in female rats.Scientific reports · 2026Article
- Downregulation of USP9X in the DG Region of the Hippocampus Leads to AD-Like Cognitive Dysfunction in Mice.CNS neuroscience & therapeutics · 2025Article
- Preoperative Sleep Deprivation Exacerbates Anesthesia/Surgery-induced Abnormal GABAergic Neurotransmission and Neuronal Damage in the Hippocampus in Aged Mice.Molecular neurobiology · 2025Article
- Brain-Wide Neuroregenerative Gene Therapy Improves Cognition in a Mouse Model of Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Repetitive Transcranial Magnetic Stimulation-Mediated Neuroprotection in the 5xFAD Mouse Model of Alzheimer's Disease Through GABRG2 and SNAP25 Modulation.Molecular neurobiology · 2025Article
- Investigating the Impact of IL-6 and CXCL8 on Neurodegeneration and Cognitive Decline in Alzheimer Disease.The international journal of neuropsychopharmacology · 2024Article
- Haploinsufficiency and Alzheimer's Disease: The Possible Pathogenic and Protective Genetic Factors.International journal of molecular sciences · 2024Review
- HIF-1α Pathway Orchestration by LCN2: A Key Player in Hypoxia-Mediated Colitis Exacerbation.Inflammation · 2024Article
- Behaviour Hallmarks in Alzheimer's Disease 5xFAD Mouse Model.International journal of molecular sciences · 2024Review
- Identification of the Shared Gene Signatures Between Alzheimer's Disease and Diabetes-Associated Cognitive Dysfunction by Bioinformatics Analysis Combined with Biological Experiment.Journal of Alzheimer's disease : JAD · 2024Article
- Transplantation of neural stem progenitor cells from different sources for severe spinal cord injury repair in rat.Bioactive materials · 2023Article
- Dulaglutide Improves Gliosis and Suppresses Apoptosis/Autophagy Through the PI3K/Akt/mTOR Signaling Pathway in Vascular Dementia Rats.Neurochemical research · 2023Article
- Investigating the Role of GABA in Neural Development and Disease Using Mice Lacking GAD67 or VGAT Genes.International journal of molecular sciences · 2022Review
- Olfactory Evaluation in Alzheimer's Disease Model Mice.Brain sciences · 2022Review
- Fatty Acid Binding Protein 3 (FABP3) and Apolipoprotein E4 (ApoE4) as Lipid Metabolism-Related Biomarkers of Alzheimer's Disease.Journal of clinical medicine · 2021Article
- Olfactory impairment in men and mice related to aging and amyloid-induced pathology.Pflugers Archiv : European journal of physiology · 2021Review
- Enhancing GABAergic signaling ameliorates aberrant gamma oscillations of olfactory bulb in AD mouse models.Molecular neurodegeneration · 2021Article
- Metabolic, Phenotypic, and Neuropathological Characterization of the Tg4-42 Mouse Model for Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2021Article
- Alterations in odor hedonics in the 5XFAD Alzheimer's disease mouse model and the influence of sex.Behavioral neuroscience · 2020Article
- GABAergic Inhibitory Interneuron Deficits in Alzheimer's Disease: Implications for Treatment.Frontiers in neuroscience · 2020Review
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundAlzheimer's disease (AD) is the most common age-related neurodegenerative disorder, affecting millions of people worldwide. Although dysfunction of multiple neurotransmitter systems including cholinergic, glutamatergic and GABAergic systems has been associated with AD progression the underlying mechanisms remain elusive. We and others have recently found that GABA content is elevated in AD brains and linked to cognitive deficits in AD mouse models. The glutamic acid decarboxylase 67 (GAD67) is the major enzyme converting glutamate into GABA and has been implied in a number of neurological disorders such as epilepsy and schizophrenia. However, whether Gad67 is involved in AD pathology has not been well studied. Here, we investigate the functional role of GAD67 in an AD mouse model with Gad67 haploinsufficiency that is caused by replacing one allele of Gad67 with green fluorescent protein (GFP) gene during generation of GAD67-GFP mice.
methodsTo genetically reduce GAD67 in AD mouse brains, we crossed the Gad67 haploinsufficient mice (GAD67-GFP
resultsWe found that reduction of GAD67 resulted in a significant decrease of amyloid β production in 5xFAD mice. Concurrently, the abnormal astrocytic GABA and tonic GABA currents, as well as the microglial reactivity were significantly reduced in the 5xFAD mice with Gad67 haploinsufficiency. Importantly, the olfactory memory deficit of 5xFAD mice was rescued by Gad67 haploinsufficiency.
conclusionsOur results demonstrate that GAD67 plays an important role in AD pathology, suggesting that GAD67 may be a potential drug target for modulating the progress of AD.
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