Age-related changes in cerebellar and hypothalamic function accompany non-microglial immune gene expression, altered synapse organization, and excitatory amino acid neurotransmission deficits

Stephen J. Bonasera, Jyothi Arikkath, Michael D. Boska, Tammy R. Chaudoin, Nicholas W. DeKorver, Evan H. Goulding, Traci A. Hoke, Vahid Mojtahedzedah, Crystal D. Reyelts, Balasrinivasa Sajja, A. Katrin Schenk, Laurence H. Tecott, Tiffany A. Volden

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

We describe age-related molecular and neuronal changes that disrupt mobility or energy balance based on brain region and genetic background. Compared to young mice, aged C57BL/6 mice exhibit marked locomotor (but not energy balance) impairments. In contrast, aged BALB mice exhibit marked energy balance (but not locomotor) impairments. Age-related changes in cerebellar or hypothalamic gene expression accompany these phenotypes. Aging evokes upregulation of immune pattern recognition receptors and cell adhesion molecules. However, these changes do not localize to microglia, the major CNS immunocyte. Consistent with a neuronal role, there is a marked age-related increase in excitatory synapses over the cerebellum and hypothalamus. Functional imaging of these regions is consistent with age-related synaptic impairments. These studies suggest that aging reactivates a developmental program employed during embryogenesis where immune molecules guide synapse formation and pruning. Renewed activity in this program may disrupt excitatory neurotransmission, causing significant behavioral deficits.

Original languageEnglish (US)
Pages (from-to)2153-2181
Number of pages29
JournalAging
Volume8
Issue number9
DOIs
StatePublished - 2016

Keywords

  • Aging
  • Cerebellum
  • Feeding
  • Hypothalamus
  • Microarray
  • Mouse physical activity
  • Pattern recognition receptor (PRR)

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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    Bonasera, S. J., Arikkath, J., Boska, M. D., Chaudoin, T. R., DeKorver, N. W., Goulding, E. H., Hoke, T. A., Mojtahedzedah, V., Reyelts, C. D., Sajja, B., Schenk, A. K., Tecott, L. H., & Volden, T. A. (2016). Age-related changes in cerebellar and hypothalamic function accompany non-microglial immune gene expression, altered synapse organization, and excitatory amino acid neurotransmission deficits. Aging, 8(9), 2153-2181. https://doi.org/10.18632/aging.101040