TY - JOUR
T1 - Anxiety and the aging brain
T2 - Stressed out over p53?
AU - Scrable, Heidi
AU - Burns-Cusato, Melissa
AU - Medrano, Silvia
N1 - Funding Information:
We thank the many members of our laboratories, past and present, who have contributed so much to the collective ideas and activities represented in this Review. Our work is supported by grants from the National Institutes of Health and the Ellison Medical Research Foundation.
PY - 2009/12
Y1 - 2009/12
N2 - We propose a model in which cell loss in the aging brain is seen as a root cause of behavioral changes that compromise quality of life, including the onset of generalized anxiety disorder, in elderly individuals. According to this model, as stem cells in neurogenic regions of the adult brain lose regenerative capacity, worn-out, dead, or damaged neurons fail to be replaced, leaving gaps in function. As most replacement involves inhibitory interneurons, either directly or indirectly, the net result is the acquisition over time of a hyper-excitable state. The stress axis is subserved by all three neurogenic regions in the adult brain, making it particularly susceptible to these age-dependent changes. We outline a molecular mechanism by which hyper-excitation of the stress axis in turn activates the tumor suppressor p53. This reinforces the loss of stem cell proliferative capacity and interferes with the feedback mechanism by which the glucocorticoid receptor turns off neuroendocrine pathways and resets the axis.
AB - We propose a model in which cell loss in the aging brain is seen as a root cause of behavioral changes that compromise quality of life, including the onset of generalized anxiety disorder, in elderly individuals. According to this model, as stem cells in neurogenic regions of the adult brain lose regenerative capacity, worn-out, dead, or damaged neurons fail to be replaced, leaving gaps in function. As most replacement involves inhibitory interneurons, either directly or indirectly, the net result is the acquisition over time of a hyper-excitable state. The stress axis is subserved by all three neurogenic regions in the adult brain, making it particularly susceptible to these age-dependent changes. We outline a molecular mechanism by which hyper-excitation of the stress axis in turn activates the tumor suppressor p53. This reinforces the loss of stem cell proliferative capacity and interferes with the feedback mechanism by which the glucocorticoid receptor turns off neuroendocrine pathways and resets the axis.
KW - Dentate gyrus
KW - GR
KW - Glucocorticoid
KW - Glucocorticoid receptor
KW - Hippocampus
KW - Hypothalamus
KW - Neural stem cell
KW - Olfactory bulb
KW - Proliferation
KW - p21
KW - p53
UR - http://www.scopus.com/inward/record.url?scp=71549120377&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=71549120377&partnerID=8YFLogxK
U2 - 10.1016/j.bbagen.2009.09.007
DO - 10.1016/j.bbagen.2009.09.007
M3 - Review article
C2 - 19800395
AN - SCOPUS:71549120377
SN - 0304-4165
VL - 1790
SP - 1587
EP - 1591
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
IS - 12
ER -