QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, January 17, 2007, 27(3):616-626; doi:10.1523/JNEUROSCI.4464-06.2007

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (21) Citing Articles via Google Scholar Google Scholar Articles by Moseley, A. E. Articles by Lingrel, J. B Search for Related Content PubMed PubMed Citation Articles by Moseley, A. E. Articles by Lingrel, J. B

 Previous Article  |  Next Article 

Behavioral/Systems/Cognitive
Deficiency in Na,K-ATPase Isoform Genes Alters Spatial Learning, Motor Activity, and Anxiety in Mice

Amy E. Moseley,^1 * Michael T. Williams,^2 * Tori L. Schaefer,² Cynthia S. Bohanan,¹ Jon C. Neumann,¹ Michael M. Behbehani,³ Charles V. Vorhees,² and Jerry B Lingrel¹

¹Department of Molecular Genetics, Biochemistry, and Microbiology, ²Division of Neurology, Department of Pediatrics, Cincinnati Children's Research Foundation, Cincinnati, Ohio 45229, and ³Department of Physiology, University of Cincinnati, College of Medicine, Cincinnati, Ohio 45267

Correspondence should be addressed to Dr. Jerry B Lingrel, University of Cincinnati, Department of Molecular Genetics, Biochemistry, and Microbiology, Cincinnati, OH 45267. Email: jerry.lingrel{at}uc.edu

Several disorders have been associated with mutations in Na,K-ATPase 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 1 isoform is found in many cell types, the 2 isoform is predominantly expressed in astrocytes, and the 3 isoform is exclusively expressed in neurons. Here we show that mice heterozygous for the 2 isoform display increased anxiety-related behavior, reduced locomotor activity, and impaired spatial learning in the Morris water maze. Mice heterozygous for the 3 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 1 isoform mice showed increased locomotor response to methamphetamine and increased basal and stimulated corticosterone in plasma. The learning and memory deficits observed in the 2 and 3 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.

Key words: knock-out mice; learning and memory; learning memory; Morris water maze; movement (motion, motor activity); Na,K- ATPase; NMDA receptor

---

Received May 15, 2006; revised Dec. 8, 2006; accepted Dec. 8, 2006.

Correspondence should be addressed to Dr. Jerry B Lingrel, University of Cincinnati, Department of Molecular Genetics, Biochemistry, and Microbiology, Cincinnati, OH 45267. Email: jerry.lingrel{at}uc.edu

This article has been cited by other articles:

				S. B. Mazzone, S. M. Reynolds, N. Mori, M. Kollarik, D. G. Farmer, A. C. Myers, and B. J. Canning Selective Expression of a Sodium Pump Isozyme by Cough Receptors and Evidence for Its Essential Role in Regulating Cough J. Neurosci., October 28, 2009; 29(43): 13662 - 13671. [Abstract] [Full Text] [PDF]

				S. J. Clapcote, S. Duffy, G. Xie, G. Kirshenbaum, A. R. Bechard, V. Rodacker Schack, J. Petersen, L. Sinai, B. J. Saab, J. P. Lerch, et al. Mutation I810N in the {alpha}3 isoform of Na+,K+-ATPase causes impairments in the sodium pump and hyperexcitability in the CNS PNAS, August 18, 2009; 106(33): 14085 - 14090. [Abstract] [Full Text] [PDF]

				U. Muller The monogenic primary dystonias Brain, August 1, 2009; 132(8): 2005 - 2025. [Abstract] [Full Text] [PDF]

				E. M. Rose, J. C. P. Koo, J. E. Antflick, S. M. Ahmed, S. Angers, and D. R. Hampson Glutamate Transporter Coupling to Na,K-ATPase J. Neurosci., June 24, 2009; 29(25): 8143 - 8155. [Abstract] [Full Text] [PDF]

				D. Bousquet-Moore, X. M. Ma, E. A. Nillni, T. A. Czyzyk, J. E. Pintar, B. A. Eipper, and R. E. Mains Reversal of Physiological Deficits Caused by Diminished Levels of Peptidylglycine {alpha}-Amidating Monooxygenase by Dietary Copper Endocrinology, April 1, 2009; 150(4): 1739 - 1747. [Abstract] [Full Text] [PDF]

				L. A. Hazelwood, R. B. Free, D. M. Cabrera, M. Skinbjerg, and D. R. Sibley Reciprocal Modulation of Function between the D1 and D2 Dopamine Receptors and the Na+,K+-ATPase J. Biol. Chem., December 26, 2008; 283(52): 36441 - 36453. [Abstract] [Full Text] [PDF]

				S. Thifault, S. Ondrej, Y. Sun, A. Fortin, E. Skamene, R. Lalonde, J. Tremblay, and P. Hamet Genetic determinants of emotionality and stress response in AcB/BcA recombinant congenic mice and in silico evidence of convergence with cardiovascular candidate genes Hum. Mol. Genet., February 1, 2008; 17(3): 331 - 344. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help