Your browser doesn't support javascript.
loading
An Adaptive Role for DNA Double-Strand Breaks in Hippocampus-Dependent Learning and Memory.
Weber Boutros, Sydney; Unni, Vivek K; Raber, Jacob.
  • Weber Boutros S; Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA.
  • Unni VK; Department of Neurology, Oregon Health & Science University, Portland, OR 97239, USA.
  • Raber J; Jungers Center for Neurosciences Research, Oregon Health & Science University, Portland, OR 97239, USA.
Int J Mol Sci ; 23(15)2022 Jul 28.
Article en En | MEDLINE | ID: mdl-35955487
ABSTRACT
DNA double-strand breaks (DSBs), classified as the most harmful type of DNA damage based on the complexity of repair, lead to apoptosis or tumorigenesis. In aging, DNA damage increases and DNA repair decreases. This is exacerbated in disease, as post-mortem tissue from patients diagnosed with mild cognitive impairment (MCI) or Alzheimer's disease (AD) show increased DSBs. A novel role for DSBs in immediate early gene (IEG) expression, learning, and memory has been suggested. Inducing neuronal activity leads to increases in DSBs and upregulation of IEGs, while increasing DSBs and inhibiting DSB repair impairs long-term memory and alters IEG expression. Consistent with this pattern, mice carrying dominant AD mutations have increased baseline DSBs, and impaired DSB repair is observed. These data suggest an adaptive role for DSBs in the central nervous system and dysregulation of DSBs and/or repair might drive age-related cognitive decline (ACD), MCI, and AD. In this review, we discuss the adaptive role of DSBs in hippocampus-dependent learning, memory, and IEG expression. We summarize IEGs, the history of DSBs, and DSBs in synaptic plasticity, aging, and AD. DSBs likely have adaptive functions in the brain, and even subtle alterations in their formation and repair could alter IEGs, learning, and memory.
Asunto(s)
Palabras clave

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Roturas del ADN de Doble Cadena / Enfermedad de Alzheimer Límite: Animals Idioma: En Año: 2022 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Roturas del ADN de Doble Cadena / Enfermedad de Alzheimer Límite: Animals Idioma: En Año: 2022 Tipo del documento: Article