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[2014 Spring Life Sciences & IBB Regular Seminar]
▶Subject: GABA from reactive astrocytes impairs memory in Alzheimer disease
▶Speaker: Changjoon Justin Lee, Ph.D. (KIST)
▶Place: Life Science Bldg. #104
In Alzheimer disease, memory impairment is the most prominent feature that afflicts patients and their families. Although reactive astrocytes have been observed around amyloid plaques ever since the original findings by Dr. Alzheimer, their role in memory impairment has been poorly understood. Here, we show that reactive astrocytes aberrantly and abundantly produce inhibitory gliotransmitter GABA by monoamine oxidase-B (MAO-B), and abnormally release the GABA through Best1 channel. In the dentate gyrus of a mouse model of Alzheimer disease, the released
GABA reduces spike probability of granule cells by acting on presynaptic GABA receptors. Suppressing GABA production in reactive astrocytes with MAO-B inhibitor, selegiline, fully restores the impaired spike probability, synaptic plasticity, and learning and memory. In the postmortem brain of Alzheimer patients, astrocytic GABA and MAO-B are significantly upregulated. We propose that selective inhibition of astrocytic GABA synthesis or release may serve as an effective therapeutic strategy for treatment of memory impairment in Alzheimer disease.
▶Inquiry: Prof. Kyong Tai Kim(279-2297)
* This seminar will be given in English