Amelioration of age-related deficits in the stimulation of synapsin phosphorylation.
In a previous report we demonstrated that aged (24-26 month) rats have deficits in long-term potentiation, a form of synaptic enhancement that is dependent on protein phosphorylation (Moore et al., Hippocampus, 3:57-66; 1993). In the present study we demonstrate that aged rats have a deficit in the phosphorylation of the synaptic vesicle associated protein synapsin I. Specifically, aged animals exhibit defective phorbol ester-induced stimulation of synapsin phosphorylation at its calcium/calmodulin dependent protein kinase II sites. We also examined the effects of caloric restriction and antioxidant therapy on this age-related deficit. We found that either life-long caloric restriction or treatment with 16 mg/kg N-tert-butyl-alpha-phenylnitrone (PBN) for 2 weeks can at least partially ameliorate the age-related deficit in the phorbol ester stimulation of synapsin phosphorylation.
Eckles
K E
KE
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80220, USA.
Dudek
E M
EM
Bickford
P C
PC
Browning
M D
MD
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D004435:Eating / Q000502:physiology; D008297:Male; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D011916:Rats, Inbred F344; D016704:Synapsins / Q000378:metabolism*
D000975:Antioxidants; D016704:Synapsins; D015240:Phorbol 12,13-Dibutyrate; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases