Imbalance between GABAergic and Glutamatergic Transmission Impairs Adult Neurogenesis in an Animal Model of Alzheimer's Disease

• Published in: Cell stem cell Vol. 5; no. 6; pp. 624 - 633
• Main Authors: Sun, Binggui, Halabisky, Brian, Zhou, Yungui, Palop, Jorge J., Yu, Guiqiu, Mucke, Lennart, Gan, Li
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 04.12.2009; Cell Press
• Subjects: Adult and adolescent clinical studies; Alzheimer Disease - genetics; Alzheimer Disease - pathology; Alzheimer Disease - physiopathology; Amyloid beta-Peptides - genetics; Amyloid beta-Peptides - metabolism; Animals; Biological and medical sciences; Calcineurin Inhibitors; Cell Differentiation - drug effects; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dendritic Spines - drug effects; Dendritic Spines - pathology; Disease Models, Animal; Fundamental and applied biological sciences. Psychology; GABA-A Receptor Antagonists; Hippocampus - drug effects; Hippocampus - embryology; Hippocampus - growth & development; Hippocampus - metabolism; Hippocampus - pathology; Humans; HUMDISEASE; Medical sciences; Mice; Mice, Transgenic; Molecular and cellular biology; Neurites - drug effects; Neurites - pathology; Neurogenesis - drug effects; Neurology; Organic mental disorders. Neuropsychology; Pertussis Toxin - administration & dosage; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; STEMCELL; Synaptic Transmission - drug effects; Tacrolimus - administration & dosage; STEMCELL; HUMDISEASE; Human; Animal model; Nervous system diseases; Alzheimer disease; Central nervous system disease; Transmission; Adult; Degenerative disease; Neurogenesis; Cerebral disorder
• ISSN: 1934-5909; 1875-9777
• DOI: 10.1016/j.stem.2009.10.003

Adult neurogenesis regulates plasticity and function in the hippocampus, which is critical for memory and vulnerable to Alzheimer's disease (AD). Promoting neurogenesis may improve hippocampal function in AD brains. However, how amyloid β (Aβ), the key AD pathogen, affects the development and function of adult-born neurons remains unknown. Adult-born granule cells (GCs) in human amyloid precursor protein (hAPP) transgenic mice, an AD model, showed greater dendritic length, spine density, and functional responses than did controls early in development, but were impaired morphologically and functionally during later maturation. Early inhibition of GABA A receptors to suppress GABAergic signaling or late inhibition of calcineurin to enhance glutamatergic signaling normalized the development of adult-born GCs in hAPP mice with high Aβ levels. Aβ-induced increases in GABAergic neurotransmission or an imbalance between GABAergic and glutamatergic neurotransmission may contribute to impaired neurogenesis in AD.