Age-related changes in the levels of voltage-dependent calcium channels and other synaptic proteins in rat brain cortices.
Neurotransmitter release from synapses is one of the most important interneuronal signaling in the nervous system. We previously reported that aging decreases depolarization-induced acetylcholine release in rat brain synaptosomes. To investigate the mechanisms underlying the age-related decrements of neurotransmission, we determined the levels of the alpha1 subunit proteins of voltage-dependent calcium channels (VDCCs) and three synaptic proteins that relate to exocytotic processes using synaptosomes prepared from cerebral cortices of young (6-month-old) and aged (27-month-old) rats. Immunoblotting analyses revealed that the protein levels of alpha1A (P/Q-type) and alpha1B (N-type) subunits in aged rats were 38% and 43% lower than the levels of young rats, respectively, but the levels of the alpha1C (L-type) subunit were not different between young and aged. On the contrary, the levels of synaptotagmin-1, synaptophysin and syntaxin were not significantly different between the two age groups in the synaptosomal preparations. These results suggest that synaptic density does not change much in the cerebral cortex in normal aging, and that the reduction of P/Q-type and N-type VDCCs, both of which participate in neurotransmitter release, is one of the causes for the decrease of neurotransmission at aged synapses.
Neuronal Function Research Group, Division of Neuroscience and Brain Function, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan. iwamotom@tmig.or.jp
Machiko
M
Iwamoto
Tairo
T
Hagishita
Yoko
Y
Shoji-Kasai
Susumu
S
Ando
Yasukazu
Y
Tanaka
D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D015220:Calcium Channels / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D050765:Qa-SNARE Proteins; D051381:Rats; D013569:Synapses / Q000378:metabolism*; D016708:Synaptophysin / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism; D050863:Synaptotagmin I; D050857:Synaptotagmins
D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050765:Qa-SNARE Proteins; D016708:Synaptophysin; D050863:Synaptotagmin I; C494312:Syt1 protein, rat; D050857:Synaptotagmins