Disparities in spatial access to neurological care in Appalachia: a cross-sectional health services analysis.

Background: Appalachia is rural and socioeconomically deprived with a heavy burden of neurological disorders and poor access to healthcare providers. Rates of neurological disorders are increasing over time without equal increases in providers, indicating that Appalachian disparities are likely to worsen. Spatial access to neurological care has not been robustly explored for U.

Fasudil or genetic depletion of ROCK1 or ROCK2 induces anxiety-like behaviors.

Twenty-nine protein kinase inhibitors have been used to treat human diseases. Out of these, two are Rho-associated protein kinase (ROCK) 1 and 2 inhibitors. The ROCKs heavily influence neuronal architecture and structural plasticity, and ROCKs are putative drug targets for various brain disorders.

Distinct and complementary functions of rho kinase isoforms ROCK1 and ROCK2 in prefrontal cortex structural plasticity.

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.

Dendritic spines provide cognitive resilience against Alzheimer's disease.

Objective: Neuroimaging and other biomarker assays suggest that the pathological processes of Alzheimer's disease (AD) begin years prior to clinical dementia onset. However, some 30 to 50% of older individuals who harbor AD pathology do not become symptomatic in their lifetime. It is hypothesized that such individuals exhibit cognitive resilience that protects against AD dementia.

Rho-associated protein kinase 1 (ROCK1) is increased in Alzheimer's disease and ROCK1 depletion reduces amyloid-β levels in brain.

Alzheimer's disease (AD) is the leading cause of dementia and mitigating amyloid-β (Aβ) levels may serve as a rational therapeutic avenue to slow AD progression. Pharmacologic inhibition of the Rho-associated protein kinases (ROCK1 and ROCK2) is proposed to curb Aβ levels, and mechanisms that underlie ROCK2's effects on Aβ production are defined. How ROCK1 affects Aβ generation remains a critical barrier.

ROCK1 and ROCK2 inhibition alters dendritic spine morphology in hippocampal neurons.

Communication among neurons is mediated through synaptic connections between axons and dendrites, and most excitatory synapses occur on actin-rich protrusions along dendrites called dendritic spines. Dendritic spines are structurally dynamic, and synapse strength is closely correlated with spine morphology. Abnormalities in the size, shape, and number of dendritic spines are prevalent in neurologic diseases, including autism spectrum disorders, schizophrenia, and Alzheimer disease.

Rho Kinase Inhibition as a Therapeutic for Progressive Supranuclear Palsy and Corticobasal Degeneration.

Unlabelled: Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are neurodegenerative four-repeat tauopathies with no cure. Mitigating pathogenic tau levels is a rational strategy for tauopathy treatment, but therapeutic targets with clinically available drugs are lacking. Here, we report that protein levels of the Rho-associated protein kinases (ROCK1 and ROCK2), p70 S6 kinase (S6K), and mammalian target of rapamycin (mTOR) were increased in PSP and CBD brains.