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Behavioral Assessment of Mice with Mitochondrial CaMKII Inhibition
Author(s) -
RosaGonzález Nicole,
Joiner Meiling
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.lb418
Subject(s) - substantia nigra , oxidative stress , dopaminergic , viability assay , parkinson's disease , programmed cell death , neuroprotection , dopamine , neuroscience , lesion , reactive oxygen species , mitochondrion , biology , microbiology and biotechnology , medicine , cell , endocrinology , apoptosis , pathology , disease , biochemistry
Oxidative stress is thought to be the common underlying mechanism that leads to cellular dysfunction and demise in Parkinson's disease. Recent studies indicate that mitochondrial CaMKII (mtCamKII) activation is responsible for excess Ca 2+ uptake under stress conditions, which ultimately leads to increased levels of cell death due to over‐production of reactive oxygen species. Inhibition of mtCaMKII, by CaMKIIN, has been established to decrease cell death under stress conditions in tissues such as the heart. It remains unidentified if inhibition of mtCaMKII in the Substantia nigra can counteract the loss of dopaminergic neurons, a hallmark of Parkinson's disease. To start addressing this interrogant, we utilized the 6‐OHDA unilateral lesion of the Substantia nigra model in mice expressing CaMKIIN, the inhibitor of mtCaMKII. Assessment of cell viability, using the Trypan blue exclusion test of cell viability, as well as confocal imaging of mitochondrial shape of SH‐SY5Y cell line, was performed to validate functionality of 6‐ OHDA. After 2 weeks, training motor impairment assays including rotarod, pole descent, inverted grid and footprint analysis were performed. Preliminary results validated the detrimental effects of 6‐OHDA on SH‐SY5Y cells and showed that mtCaMKIIN‐expressing mice were slower in the pole descent test. Thus, the 6‐OHDA unilateral lesion of the Substantia nigra model in mice shows great promise to assess level of motor impairment in mice expressing mtCaMKIIN, that way, assessing if inhibition of mtCaMKII is protective against cell death. Support or Funding Information Special thanks to the lab's of Dr.'s Amy Lee, Ryan Boudreau and Nandakumar Narayanan, the Interdisciplinary Summer Undergraduate Research Program (ISURP), the PRISE program and the CCOM Office of Cultural Affairs and Diversity Initiatives. This project was supported by NIH (AL: NS084190 , DC009433 ) and a Carver MRIG (MAJ). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .