Age-specific transcriptional response to stroke

Neurobiol Aging. 2014 Jul;35(7):1744-54. doi: 10.1016/j.neurobiolaging.2014.01.012. Epub 2014 Jan 13.


Increased age is a major risk factor for stroke incidence and post-ischemic mortality. To develop age-adjusted therapeutic interventions, a clear understanding of the complexity of age-related post-ischemic mechanisms is essential. Transient occlusion of the middle cerebral artery--a model that closely resembles human stroke--was used to induce cerebral infarction in mice of 4 different ages (2, 9, 15, 24 months). By using Illumina cDNA microarrays and quantitative PCR we detected a distinct age-dependent response to stroke involving 350 differentially expressed genes. Our analyses also identified 327 differentially expressed genes that responded to stroke in an age-independent manner. These genes are involved in different aspects of the inflammatory and immune response, oxidative stress, cell cycle activation and/or DNA repair, apoptosis, cytoskeleton reorganization and/or astrogliosis, synaptic plasticity and/or neurotransmission, and depressive disorders and/or dopamine-, serotonin-, GABA-signaling. In agreement with our earlier work, aged brains displayed an attenuated inflammatory and immune response (Sieber et al., 2011) and a reduced impairment of post-stroke synaptic plasticity. Our data also revealed a distinct age-related susceptibility for post-ischemic depression, the most common neuropsychiatric consequence of stroke, which has a major influence on functional outcome.

Keywords: Aging; Depression; Inflammation; MCAO.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics*
  • Aging / immunology
  • Animals
  • Brain / immunology
  • Brain / physiopathology
  • Cell Cycle / genetics
  • DNA Repair / genetics
  • Depressive Disorder / genetics
  • Disease Models, Animal
  • Gene Expression Regulation, Developmental / genetics
  • Genetic Predisposition to Disease
  • Humans
  • Inflammation / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Targeted Therapy
  • Nerve Regeneration
  • Neuronal Plasticity / genetics
  • Oxidative Stress / genetics
  • Risk Factors
  • Stroke / drug therapy
  • Stroke / genetics*
  • Stroke / physiopathology
  • Synapses / physiology
  • Transcription, Genetic / genetics*