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

By Binggui Sun, Brian Halabisky, Yungui Zhou, J. Palop, Gui-qiu Yu, L. Mucke, L. Gan. 2009

207 citations recorded by the source corpus.

SUMMARY 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 controls early in development, but were impaired morphologically and functionally during later maturation. Early inhibition of GABAA 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.

Subfields: Cellular and Molecular Neuroscience, Developmental Neuroscience, Physiology

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Citations in the corpus

Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions (2011, background): “For example, in animal models of Alzheimer's disease, aberrant GABA signaling affects fate specification of neural progenitors and dendritic growth of newborn neurons in the aged SGZ (Li et al., 2009; Sun et al., 2009).”
Benzodiazepines And The Potential Trophic Effect Of Antidepressants On Dentate Gyrus Cells In Mood Disorders (2014, unknown): “Additionally, a balance of glutamatergic and GABAergic transmission closely regulates adult hippocampal neurogenesis (Sun et al., 2009).”
Neurodegenerative disease and adult neurogenesis (2011, background): “Longer dendrites, increased spine density and functional responses in early-stage, newly generated neurons in APP transgenic mice have recently been reported (Sun et al., 2009), possibly as compensatory mechanisms.”
Adult hippocampal neurogenesis and its role in Alzheimer's disease (2011, background): “Early inhibition of GABAergic signaling or late facilitation of glutamatergic signaling can normalize neuronal development despite the presence of high Ab levels, suggesting that abnormal GABAergic neurotransmission or an imbalance between GABAergic and glutamatergic neurotransmission may contribute”