| First Author | Kirshenbaum GS | Year | 2012 |
| Journal | Genes Brain Behav | Volume | 11 |
| Issue | 4 | Pages | 436-43 |
| PubMed ID | 22520507 | Mgi Jnum | J:198031 |
| Mgi Id | MGI:5495107 | Doi | 10.1111/j.1601-183X.2012.00800.x |
| Citation | Kirshenbaum GS, et al. (2012) Genetic suppression of agrin reduces mania-like behavior in Na+ , K+ -ATPase alpha3 mutant mice. Genes Brain Behav 11(4):436-43 |
| abstractText | Myshkin mice heterozygous for an inactivating mutation in the neuron-specific Na(+) ,K(+) -ATPase alpha3 isoform show behavior analogous to mania, including an abnormal endogenous circadian period. Agrin is a proteoglycan implicated as a regulator of synapses that has been proposed to inhibit activity of Na(+) ,K(+) -ATPase alpha3. We examined whether the mania-related behavior of Myshkin mice could be rescued by a reduction in the expression of agrin through genetic knockout. The suppression of agrin reduced hyperambulation and holeboard exploration, restored anxiety-like behavior (or reduced risk-taking behavior), improved prepulse inhibition and shortened the circadian period. Hence, agrin is important for regulating mania-like behavior and circadian rhythms. In Myshkin mice, the suppression of agrin increased brain Na(+) ,K(+) -ATPase activity by 11 +/- 4%, whereas no effect on Na(+) ,K(+) -ATPase activity was detected when agrin was suppressed in mice without the Myshkin mutation. These results introduce agrin as a potential therapeutic target for the treatment of mania and other neurological disorders associated with reduced Na(+) ,K(+) -ATPase activity and neuronal hyperexcitability. |
