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Research Paper|Volume 8, Issue 9|pp 2153—2181

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. Bonasera1, Jyothi Arikkath2, Michael D. Boska3, Tammy R. Chaudoin1, Nicholas W. DeKorver1, Evan H. Goulding4, Traci A. Hoke1, Vahid Mojtahedzedah5, Crystal D. Reyelts1, Balasrinivasa Sajja3, A. Katrin Schenk6, Laurence H. Tecott7, Tiffany A. Volden1
  • 1Division of Geriatrics, University of Nebraska Medical Center, Durham Research Center II, Omaha, NE 68198, USA
  • 2Monroe-Meyer Institute, University of Nebraska Medical Center, Durham Research Center II, Omaha, NE 68198, USA
  • 3Department of Radiology, University of Nebraska Medical Center, College of Medicine, Omaha, NE 68198, USA
  • 4Department of Psychiatry and Behavioral Sciences, Northwestern University, Chicago, IL 60611, USA
  • 5The Institute for Addiction Sciences and Psychology (IRSA), Tehran, Iran
  • 6Department of Physics, Randolph College, Lynchburg, VA 24503, USA
  • 7Department of Psychiatry, University of California, San Francisco, San Francisco, CA, 94158, USA
Received: June 8, 2016Accepted: September 7, 2016Published: September 20, 2016
https://doi.org/10.18632/aging.101040

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.