| First Author | Greathouse KM | Year | 2018 |
| Journal | Brain Struct Funct | Volume | 223 |
| Issue | 9 | Pages | 4227-4241 |
| PubMed ID | 30196430 | Mgi Jnum | J:268041 |
| Mgi Id | MGI:6270285 | Doi | 10.1007/s00429-018-1748-4 |
| Citation | Greathouse KM, et al. (2018) Distinct and complementary functions of rho kinase isoforms ROCK1 and ROCK2 in prefrontal cortex structural plasticity. Brain Struct Funct 223(9):4227-4241 |
| abstractText | Rho-associated protein kinases (ROCK) 1 and 2 are attractive drug targets for a range of neurologic disorders; however, a critical barrier to ROCK-based therapeutics is ambiguity over whether there are isoform-specific roles for ROCKs in neuronal structural plasticity. Here, we used a genetics approach to address this long-standing question by analyzing both male and female adult ROCK1(+/-) and ROCK2(+/-) mice compared to littermate controls. Individual pyramidal neurons in the medial prefrontal cortex (mPFC) were targeted for iontophoretic microinjection of fluorescent dye, followed by high-resolution confocal microscopy and neuronal 3D reconstructions for morphometry analysis. Increased apical and basal dendritic length and intersections were observed in ROCK1(+/-) but not ROCK2(+/-) mice. Although dendritic spine densities were comparable among genotypes, apical spine length was decreased in ROCK1(+/-) but increased in ROCK2(+/-) mice. Spine head and neck diameter were reduced similarly in ROCK1(+/-) and ROCK2(+/-) mice; however, certain spine morphologic subclasses were more affected than others in a genotype-dependent manner. Biochemical analyses of ROCK substrates in synaptic fractions revealed that phosphorylation of LIM kinase and cofilin were reduced in ROCK1(+/-) and ROCK2(+/-) mice, while phosphorylation of myosin light chain was decreased exclusively in ROCK1(+/-) mice. Collectively, these observations implicate ROCK1 as a novel regulatory factor of neuronal dendritic structure and detail distinct and complementary roles of ROCKs in mPFC dendritic spine structure. |
