Publication Date

2015

Document Type

Thesis

Committee Members

Mauricio Di Fulvio (Committee Member), Nadja Grobe (Committee Member), James B. Lucot (Advisor)

Degree Name

Master of Science (MS)

Abstract

The NKCC2A is a splice variant of the Na+K+2Cl- co-transporter 2 (Slc12a1), which is abundantly expressed in macula densa and in the apical membrane of the tubular cells in the kidney. Most of our knowledge regarding NKCC2 function is limited to the kidney, the organ where NKCC2 is abundantly expressed. However, recent studies have demonstrated that NKCC2 is also expressed in extra-renal tissues. This study was designed to determine if NKCC2A, a splice variant of NKCC2 has an impact on behavior and nervous system activity of mice. To these ends, we used mice (wild type, WT), lacking a single or both alleles of NKCC2A (heterozygous, HE and homozygous, HO, respectively) which were subjected to battery of standardized behavioral tests. NKCC2A-HO mice exhibited a significant gating impairment when compared to the WT or HE genotypes. Interestingly, NKCC2A-HO mice also exhibited a significantly lower immobility time compared to the WT and HE mice in the forced swim test (FST), a finding that could not be reproduced in the tail suspension test (TST). Nevertheless, the caudate nucleus of NKCC2A-HO mice exhibited low content of serotonin (5-HT) and dopamine metabolites, which might account for the reduced immobility time assayed by the FST. NKCC2A-HO mice had significantly lower levels of epinephrine (EPI) and norepinephrine (NE) in the adrenals, with the HE mice having intermediate levels suggesting a role of NKCC2A in sympathetic activity, a conclusion suggested by the finding that these mice excreted low urinary EPI and NE. Together, the results of this study indicate that NKCC2A impacts behavior and neurochemistry in specific regions of the brain and the periphery.

Page Count

76

Department or Program

Department of Pharmacology and Toxicology

Year Degree Awarded

2015

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