Synapsin-I- and synapsin-II-null mice display an increased age-dependent cognitive impairment.
Synapsin I (SynI) and synapsin II (SynII) are major synaptic vesicle (SV) proteins that function in the regulation of the availability of SVs for release in mature neurons. SynI and SynII show a high level of sequence similarity and share many functions in vivo, although distinct physiological roles for the two proteins have been proposed. Both SynI(-/-) and SynII(-/-) mice have a normal lifespan, but exhibit a decreased number of SVs and synaptic depression upon high-frequency stimulation. Because of the role of the synapsin proteins in synaptic organization and plasticity, we studied the long-lasting effects of synapsin deletion on the phenotype of SynI(-/-) and SynII(-/-) mice during aging. Both SynI(-/-) and SynII(-/-) mice displayed behavioural defects that emerged during aging and involved emotional memory in both mutants, and spatial memory in SynII(-/-) mice. These abnormalities, which were more pronounced in SynII(-/-) mice, were associated with neuronal loss and gliosis in the cerebral cortex and hippocampus. The data indicate that SynI and SynII have specific and non-redundant functions, and that synaptic dysfunctions associated with synapsin mutations negatively modulate cognitive performances and neuronal survival during senescence.
Corradi
Anna
A
Department of Experimental Medicine, University of Genova and Istituto Nazionale di Neuroscienze, Viale Benedetto XV, 3 16132 Genova, Italy.
Zanardi
Alessio
A
Giacomini
Caterina
C
Onofri
Franco
F
Valtorta
Flavia
F
Zoli
Michele
M
Benfenati
Fabio
F
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology*; D003072:Cognition Disorders / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007858:Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D008569:Memory Disorders / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity; D019579:Neocortex / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000473:pathology / Q000502:physiology; D009483:Neuropsychological Tests; D016704:Synapsins / Q000235:genetics / Q000378:metabolism*
D016704:Synapsins