Akting up in the GABA hypothesis of schizophrenia: Akt1 deficiency modulates GABAergic functions and hippocampus-dependent functions

• DOI: 10.1038/srep33095
• Publication Date: 2016-09-12T10:18:09Z
• Authors: Chia-Yuan Chang; Yi-Wen Chen; Tsu-Wei Wang; Wen-Sung Lai
• Keywords: Male; Mice, Knockout; Pyramidal Cells; Cell Count; Cell Differentiation; Convulsants; Receptors, GABA-A; Brain Waves; Hippocampus; Article; GABA Antagonists; 03 medical and health sciences; Parvalbumins; 0302 clinical medicine; Interneurons; Schizophrenia; Animals; Pentylenetetrazole; Female; Schizophrenic Psychology; GABAergic Neurons; Maze Learning; Proto-Oncogene Proteins c-akt

Accumulating evidence implies that both AKT1 and GABAA receptor (GABAAR) subunit genes are involved in schizophrenia pathogenesis. Activated Akt promotes GABAergic neuron differentiation increases GABAAR expression on the plasma membrane. To elucidate role of Akt1 modulating functions schizophrenia-related cognitive deficits, a set 6 vitro vivo experiments was conducted. First, an Akt1/2 inhibitor applied to evaluate its effect neuron-like cell formation from P19 cells. Inhibiting resulted reduction parvalbumin-positive In Akt1(-/-) wild-type mice, seizures induced using pentylenetetrazol (a antagonist) were measured, interneuron abundance brain examined. Female but not male exhibited less pentylenetetrazol-induced convulsive activity than their corresponding controls. Reduced expression, especially hippocampus, also observed female mice compared mice. Neuromorphometric analyses revealed significantly reduced neurite complexity hippocampal pyramidal neurons. Additionally, displayed increased oscillation power impaired spatial memory Our findings suggest deficiency modulates interneurons contributing hippocampus-dependent functional impairment.