Anxiety and the aging brain: Stressed out over p53?

Heidi Scrable, Melissa Burns-Cusato, Silvia Medrano

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1587-1591
Number of pages5
JournalBiochimica et Biophysica Acta - General Subjects
Volume1790
Issue number12
DOIs
StatePublished - Dec 2009

    Fingerprint

Keywords

  • Dentate gyrus
  • Glucocorticoid
  • Glucocorticoid receptor
  • GR
  • Hippocampus
  • Hypothalamus
  • Neural stem cell
  • Olfactory bulb
  • p21
  • p53
  • Proliferation

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this