期刊
BEHAVIOURAL BRAIN RESEARCH
卷 157, 期 2, 页码 219-234出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbr.2004.07.002
关键词
brain-type creatine kinase; ubiquitous mitochondrial creatine kinase; double knockout mice; brain morphology; cellular metabolic energy; behavioural testing
The cytosolic brain-type creatine kinase (BCK) isoform and the rnitochondrial ubiquitous creatine kinase (UbCKmit) isoform are both important for the maintenance and distribution of cellular energy in neurons and astrocytes. Previously, we reported that mice deficient for BCK or UbCKmit each showed a surprisingly mild phenotype, probably due to reciprocal functional compensation by the remaining creatine kinase. This study shows that adult male mice lacking both creatine kinase isoforms (CK- -/- - double knockout mice) have a reduced body weight, and demonstrate a severely impaired spatial learning in both a dry and a wet maze, lower nestbuilding activity and diminished acoustic startle reflex responses when compared to age-matched male wildtype mice with the same genetic background. In contrast, their visual and motor functions, exploration behaviour, prepulse inhibition and anxiety-related responses were not changed, suggesting no global deficit in sensorimotor function, hearing or motivation. Morphological analysis of CK- -/- - double knockout brains revealed a reduction of similar to7% in wet brain weight and hippocampal size, a similar to15% smaller regio-inferior and relatively larger supra-pyramidal, and intra-infra-pyramidal mossy fiber areas. These results suggest that lack of both brain specific creatine kinase isoforms renders the synaptic circuitry in adult brain less efficient in coping with sensory or cognitive activity related challenges. (C) 2004 Elsevier B.V. All rights reserved.
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