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- Title
Deficiency in Na,K-ATPase α Isoform Genes Alters Spatial Learning, Motor Activity, and Anxiety in Mice.
- Authors
Moseley, Amy E.; Williams, Michael T.; Schaefer, Tori L.; Bohanan, Cynthia S.; Neumann, Jon C.; Behbehani, Michael M.; Vorhees, Charles V.; Lingrel, Jerry B.
- Abstract
Several disorders have been associated with mutations in Na,K-ATPase α isoforms (rapid-onset dystonia parkinsonism, familial hemiplegic migraine type-2), as well as reduction in Na,K-ATPase content (depression and Alzheimer's disease), thereby raising the issue of whether haploinsufficiency or altered enzymatic function contribute to disease etiology. Three isoforms are expressed in the brain: the α1 isoform is found in many cell types, the α2 isoform is predominantly expressed in astrocytes, and the α3 isoform is exclusively expressed in neurons. Here we show that mice heterozygous for the α2 isoform display increased anxiety-related behavior, reduced locomotor activity, and impaired spatial learning in the Morris water maze. Mice heterozygous for the α3 isoform displayed spatial learning and memory deficits unrelated to differences in cued learning in the Morris maze, increased locomotor activity, an increased locomotor response to methamphetamine, and a 40% reduction in hippocampal NMDA receptor expression. In contrast, heterozygous α1 isoform mice showed increased locomotor response to methamphetamine and increased basal and stimulated corticosterone in plasma. The learning and memory deficits observed in the α2 and α3 heterozygous mice reveal the Na,K-ATPase to be an important factor in the functioning of pathways associated with spatial learning. The neurobehavioral changes seen in heterozygous mice suggest that these mouse models may be useful in future investigations of the associated human CNS disorders.
- Subjects
MICE; LEARNING; MEMORY; MOTION; SODIUM; ADENOSINE triphosphate; METHYL aspartate
- Publication
Journal of Neuroscience, 2007, Vol 27, Issue 3, p616
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.4464-06.2007