BioProject

We describe age-related molecular and neuronal changes that disrupt mobility or energy balance based on brain region and genetic background. More...

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. keywords: aging, C57BL/6, BALB, CBA, hypothalamus, cerebellum, striatum, frontal cortex Overall design: In our cited manuscript, we examined age-associated changes in gene expression in two mouse strains (C57BL/6, BALB) at three ages (2-3 mo, 12-13 mo, 21-24 mo), and at two sites (whole tissue hypothalamus and cerebellum). Biological replicates were as follows: BALB hypothalamus, 2-3 mo, n=7; 12-13 mo, n=5; 20-23 mo, n=6; C57BL/6 hypothalamus, 2-3 mo, n=5; 22-24 mo, n=5; BALB cerebellum, 2-3 mo, n=5; 12-13 mo, n=6, 21-23 mo, n=4; C57BL/6 cerebellum, 2-3 mo, n=4, 12-13 mo, n=2, 21-23 mo, n=6. We also provide additional unpublished data describing age-related changes in gene expression for the frontal cortex of 2-3 mo (n=8) and 15-16 mo old (n=8) female BALB mice, for the striatum of 2-3 mo old (n=3), 12-13 mo old (n=5), and 21-23 mo old (n=5) male BALB mice, and for the hypothalamus of 2-3 mo old (n=7), 12-13 mo old (n=5), and 21-23 mo old (n=8) male CBA mice. -------------------------------------- The authors are unable to locate the raw data for the following 8 samples: BALB-frontalcortex-young-3 BALB-frontalcortex-young-5 BALB-frontalcortex-young-6 BALB-frontalcortex-young-7 BALB-frontalcortex-old-1 BALB-frontalcortex-old-3 BALB-frontalcortex-old-4 BALB-frontalcortex-old-7 However, the authors state that this has the complete data for the manuscript. Less...