The mechanisms behind individual variability that lead only some individuals to develop stress-related psychopathologies are one of the key questions in stress research today. Here, we explore the contribution of one target molecule, the GABA synthetic enzyme glutamic acid decarboxylase (GAD) 65, to mechanisms of vulnerability and resilience. GAD65 is critically involved in the activity-dependent regulation of GABAergic inhibition in the central nervous system. It is also required for the maturation of the GABAergic system during adolescence, a period that is critical for the development of several neuropsychiatric diseases. Mice bearing a null mutation of the GAD65 gene develop hyperexcitability of the amygdala and hippocampus, and a phenotype of increased anxiety and pathological fear memory reminiscent of posttraumatic stress disorder. However, GAD65 haplodeficiency, which results in delayed postnatal increase of GABA levels, provides resilience to juvenile stress induced anxiety. Results obtained so far clearly indicate that GAD65 functioning is relevant to both stress vulnerability and stress resilience. The variable results regarding stress-related alterations in the expression of GAD65, together with the differences between effects of homozygous GAD65(-/-) knockout and GAD65 haplodeficiency, suggest that the role of GAD65 in stress vulnerability and resilience may differ in different brain regions and developmental stages. More temporal- and spatial-specific manipulations of expression are required to more accurately describe the role played by this enzyme in coping with stress. This is also important when examining the role of other target molecules in individual differences related to stress vulnerability and resilience.
|Title of host publication||Stress Resilience|
|Subtitle of host publication||Molecular and Behavioral Aspects|
|Number of pages||12|
|ISBN (Electronic)||9780128139844, 9780128139837|
|ISBN (Print)||9780128139837, 9780128139844|
|State||Published - 1 Nov 2019|
Bibliographical notePublisher Copyright:
© 2020 Elsevier Inc. All rights reserved.
- Individual differences
- Stress resilience
ASJC Scopus subject areas
- Medicine (all)
- Neuroscience (all)