Involvement of the GABAergic system in depressive symptoms of Alzheimer's disease.
Cognitive and neuropsychiatric (BPSD) symptoms seen in Alzheimer's disease (AD) probably result from differential neurotransmitter alterations. The involvement of the glutamatergic and GABAergic system in cognitive and behavioral and psychological symptoms of dementia (BPSD) has been studied in post-mortem frontal and temporal cortex from AD patients who had been prospectively assessed with the Mini-Mental State Examination (MMSE) for cognitive impairment and with the Present Behavioral Examination (PBE) for BPSD. In addition to cholinergic deficits, significant decreases in gamma-amino butyric acid (GABA) content, with no changes in glutamate content, were found in frontal and temporal cortex. Both GABA levels and the glutamate/GABA ratio showed significant correlations with depression in AD. In the temporal cortex, higher densities of GABA(A)/benzodiazepine receptors also correlated with more severe depression. It can be suggested that in a situation of cholinergic deficit, such as AD, an imbalance between the excitatory glutamatergic tone and inhibitory GABAergic tone may be responsible for non-cognitive behavioral disturbances.
Department of Pharmacology, School of Medicine, Center for Applied Medical Research, University of Navarra, Irunlarrea 1, 31008 Pamplona, Spain.
Monica
M
Garcia-Alloza
Shirley W
SW
Tsang
Francisco J
FJ
Gil-Bea
Paul T
PT
Francis
Mitchell K
MK
Lai
Beatriz
B
Marcos
Christopher P
CP
Chen
María J
MJ
Ramirez
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D003072:Cognition Disorders / Q000378:metabolism*; D003863:Depression / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D018079:Receptors, GABA / Q000378:metabolism*; D014018:Tissue Distribution; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018079:Receptors, GABA; D005680:gamma-Aminobutyric Acid