Synapsin-I- and synapsin-II-null mice display an increased age-dependent cognitive impairment

• Published in: Journal of cell science Vol. 121; no. 18; pp. 3042 - 3051
• Main Authors: Corradi, Anna, Zanardi, Alessio, Giacomini, Caterina, Onofri, Franco, Valtorta, Flavia, Zoli, Michele, Benfenati, Fabio
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Limited 15.09.2008
• Subjects: Animals; Behavior, Animal - physiology; Cellular Senescence - physiology; Cognition Disorders - metabolism; Hippocampus - metabolism; Hippocampus - pathology; Learning - physiology; Memory - physiology; Memory Disorders - physiopathology; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor Activity; Neocortex - metabolism; Neocortex - pathology; Neurons - pathology; Neurons - physiology; Neuropsychological Tests; Synapsins - genetics; Synapsins - metabolism
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.035063

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.