Effects of SPAK knockout on sensorimotor gating, novelty exploration, and brain area-dependent expressions of NKCC1 and KCC2 in a mouse model of schizophrenia

Progress in Neuro-psychopharmacology & Biological Psychiatry
Sung-Sen YangYia-Ping Liu

Abstract

SPAK (Sterile 20/SPS1-related proline/alanine-rich kinase) is a protein kinase belonging to the mitogen-activated protein kinase (MAPK) superfamily that has been found to be extensively distributed across the body. The SPAK downstream substrates NKCC1 and KCC2 in the central nervous system are important in the interpretation of developmental mental disorders. The present study aimed to clarify the role of SPAK-NKCC1/KCC2 using a rodent schizophrenia-like model. The mouse paradigm of isolation rearing (IR) was employed, as it simulates the sensorimotor gating abnormalities of schizophrenia. SPAK transgenic mice were used and were divided into four groups: social-wild type, social-SPAK(-/-), isolation-wild type, and isolation-SPAK(-/-). The prepulse inhibition (PPI) test and the novel object recognition test (NORT) were used to measure schizophrenia-associated dysfunctions in gating ability and the novelty recognition, respectively. Finally, the protein expressions of NKCC1/KCC2 in the prefrontal cortex and hippocampus were detected to determine correlations with the behavioral data. Our results demonstrated that SPAK-null mice had superior PPI and novelty recognition relative to wild type controls, with a concomitant increase in...Continue Reading

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Citations

Jun 7, 2015·Medical Hypotheses·Yu-Yin YangYia-Ping Liu
Aug 6, 2016·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Chen-Cheng LinYia-Ping Liu
Oct 23, 2016·Free Radical Biology & Medicine·Tsai-Jung LinShuk-Man Ka
Feb 11, 2016·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Hanshu ZhaoDandan Sun
Apr 15, 2016·American Journal of Physiology. Renal Physiology·Mohammed Z Ferdaus, James A McCormick
Jun 8, 2021·Acta Pharmaceutica Sinica. B·Nur Farah Meor AzlanJinwei Zhang

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