A C Godshall | PubMed Health

PubMed1993

Age-related changes in neural cell adhesion molecule (NCAM) isoforms in the mouse telencephalon.

The concentrations of different polypeptide isoforms of the neural cell adhesion molecule NCAM were examined in telencephalic and brainstem-cerebellar tissue from groups of young (3 months) and old (25 months) mice. Antibodies against chick brain NCAM were used in immunoblot analyses to quantify 180 (NCAM180) and 140 (NCAM140) kDa NCAM forms in mouse brain samples containing equal amounts of protein. Telencephalic homogenates from the older group exhibited 37% and 31% less NCAM180 and NCAM140 immunoreactivity, respectively, when compared with homogenates from the younger animals. Brainstem-cerebellar homogenates, however, did not express such age-related changes in the two NCAM isoforms. Age-related changes in isoforms labeled by the anti-NCAM antibodies were not evident in synaptic plasma membranes. NCAM180:NCAM140 ratios were 2- to 3-fold greater in the synaptic membranes vs. homogenates for both age groups. These data suggest that expression levels of NCAM180 and NCAM140 are selectively impaired with aging in the telencephalon, whereas the synaptic contents of these molecules appear to be stably regulated.

Aging↗

PubMed1992

Mouse telencephalon exhibits an age-related decrease in glutamate (AMPA) receptors but no change in nerve terminal markers.

The central excitatory amino acid receptor selective for alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) was examined in brain tissue from mice at 3 and 25 months after birth. Antibodies against the rat GluR-A glutamate receptor subunit (selective for kainate and AMPA) labeled a mouse brain component of about M(r) 100,000. Telencephalic tissue from the older group of mice exhibited 31% less immunoreactivity towards this component as compared with that from the young group. Binding of [3H]AMPA also decreased with age in the telencephalon to an extent which was similar to the loss of receptor immunoreactivity. Scatchard analysis revealed that this reduction is due to a decrease in receptor density and not to a change in binding affinity. In contrast, there were only small age-related changes in AMPA receptor immunoreactivity and binding levels in the brain stem and cerebellum. Binding to dopamine, serotonin, or GABA receptors was not significantly reduced in the older mice. Since the nerve terminal markers synaptophysin and the SV2 glycoprotein were not detectably different in the two groups of mice, the age-related reduction in AMPA receptors is not likely to be due to a general decrease in synaptic density. These data suggest that glutamatergic neurotransmission mediated by AMPA-type receptors is selectively impaired with aging in the telencephalon.

Aging↗