Homeostatic disinhibition in the aging brain and Alzheimer's disease.

摘要: In this article we propose that impaired efficiency of glutamatergic synaptic transmission and a compensatory reduction in inhibitory neurotransmission, process called homeostatic dishinhibition, occurs the aging brain more dramatically Alzheimer’s disease (AD). Homeostatic disinhibition may help understand certain features AD including: 1) increased risk for epileptic seizures, especially early phase disease; 2) reduced ability to generate γ-oscillations 3) increase neuronal activity as measured by functional MRI. be major mechanism activates cognitive reserve. Modulating therefore viable therapeutic strategy can complement existing anti-amyloid strategies. Specifically, enhancing endogenous through co-agonist signaling or positive allosteric modulation metabotropic receptors appears an attractive strategy. Alternatively, further GABAergic work well, although care has taken prevent seizures.