Age-related changes in cerebellar and hypothalamic function accompany non-microglial immune gene expression, altered synapse organization, and excitatory amino acid neurotransmission deficits.
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.
Division of Geriatrics, University of Nebraska Medical Center, Durham Research Center II, Omaha, NE 68198, USA.
Stephen J
SJ
Bonasera
Monroe-Meyer Institute, University of Nebraska Medical Center, Durham Research Center II, Omaha, NE 68198, USA.
Jyothi
J
Arikkath
Department of Radiology, University of Nebraska Medical Center, College of Medicine, Omaha, NE 68198, USA.
Michael D
MD
Boska
Division of Geriatrics, University of Nebraska Medical Center, Durham Research Center II, Omaha, NE 68198, USA.
Tammy R
TR
Chaudoin
Division of Geriatrics, University of Nebraska Medical Center, Durham Research Center II, Omaha, NE 68198, USA.
Nicholas W
NW
DeKorver
Department of Psychiatry and Behavioral Sciences, Northwestern University, Chicago, IL 60611, USA.
Evan H
EH
Goulding
Division of Geriatrics, University of Nebraska Medical Center, Durham Research Center II, Omaha, NE 68198, USA.
Traci A
TA
Hoke
The Institute for Addiction Sciences and Psychology (IRSA), Tehran, Iran.
Vahid
V
Mojtahedzedah
Division of Geriatrics, University of Nebraska Medical Center, Durham Research Center II, Omaha, NE 68198, USA.
Crystal D
CD
Reyelts
Department of Radiology, University of Nebraska Medical Center, College of Medicine, Omaha, NE 68198, USA.
Balasrinivasa
B
Sajja
Department of Physics, Randolph College, Lynchburg, VA 24503, USA.
A Katrin
AK
Schenk
Department of Psychiatry, University of California, San Francisco, San Francisco, CA, 94158, USA.
Laurence H
LH
Tecott
Division of Geriatrics, University of Nebraska Medical Center, Durham Research Center II, Omaha, NE 68198, USA.
Tiffany A
TA
Volden
D000375:Aging / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D000818:Animals; D002531:Cerebellum / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology; D018846:Excitatory Amino Acids / Q000502:physiology*; D015870:Gene Expression; D007031:Hypothalamus / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
D018846:Excitatory Amino Acids
aging; cerebellum; feeding; hypothalamus; microarray; mouse physical activity; pattern recognition receptor (PRR)
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