Figure 1.

Altered GABAergic neurotransmission in both genetic epilepsy and Alzheimer’s disease. The neurotransmitter GABA can be released from both neurons and glia. GABA is synthesized from glutamic acid, the principal excitatory neurotransmitter via glutamic acid decarboxylase (GAD). GABA is catabolized by GABA transaminase (GABA-T), which is a membrane-bound enzyme expressed by neurons and glia. In GABAergic interneurons, GABA is released from vesicles in presynaptic terminals and activates GABA receptors, which include GABA_A receptors and GABA_B receptors. Under pathological conditions, such as AD, GABA can also be released from reactive astrocytes. GABA_A receptors hyperpolarize neurons via Cl⁻ influx. The released GABA is taken up by GABA transporters (GAT-1 and GAT-3) back into presynaptic compartments of neurons or into astrocytes. Failure of GABA clearance due to malfunctioning GABA transporters or excessive GABA production by reactive astrocytes will alter GABAergic neurotransmission, leading to a seizure-prone brain state [90].