A simple, efficient tool for assessment of mice after unilateral cortex injury.

A refined battery of neurological tests, SNAP (Simple Neuroassessment of Asymmetric Impairment), was developed and validated to efficiently assess neurological deficits induced in a mouse model of traumatic brain injury. Four to 7-month old mice were subjected to unilateral controlled cortical impact or sham injury (craniectomy only). Several behavioral tests (SNAP, beam walk, foot fault, and water maze) were used to assess functional deficits. SNAP was unique among these in that it required no expensive equipment and was performed in less than 5 min per mouse. SNAP demonstrated a high level of sensitivity and specificity as determined by receiver-operator characteristics curve analysis. Interrater reliability was good, as determined by Cohen's Kappa method and by comparing the sensitivity and specificity across various raters. SNAP detected deficits in proprioception, visual fields, and motor strength in brain-injured mice at 3 days, and was sensitive enough to detect magnitude and recovery of injury. The contribution of individual battery components changed as a function of time after injury, however, each was important to the overall SNAP score. SNAP provided a sensitive, reliable, time-efficient and cost-effective means of assessing neurological deficits in mice after unilateral brain injury.

Cyclin-dependent kinase-5 in neurodegeneration.

Cyclin-dependent kinase-5 (CDK5) is predominantly active in the nervous system and it is well established that CDK5 is essential in neuronal development. In addition to its recognized role in development, there is increasing evidence that CDK5 may be involved in the pathogenesis of several neurodegenerative disorders. Although studies have shown that CDK5 can modulate cell death and survival, controversy still exists as to the exact role CDK5 may play in neurodegenerative processes. This review will highlight recent data on the possible roles of CDK5 in neurodegeneration.

Effects of cyclin-dependent kinase-5 activity on apoptosis and tau phosphorylation in immortalized mouse brain cortical cells.

Cyclin-dependent kinase-5 (CDK5), a unique CDK family member, is active primarily in the central nervous system (CNS). Previous studies suggest that CDK5 is proapoptotic and contributes to tau hyperphosphorylation and neurodegeneration in Alzheimer's disease. The objective of this study was to examine CDK5 effects on apoptotic progression and tau phosphorylation. Immortalized embryonic mouse brain cortical cells were used to establish a stable cell line that overexpressed wild-type human tau. In these studies, thapsigargin, which induces endoplasmic reticulum stress and can cause accumulation of misfolded proteins, was used to induce apoptosis. Caspase-3 activity and poly-(ADP-ribose)-polymerase (PARP) cleavage, as measures of apoptosis, were significantly increased 24 and 48 hr after thapsigargin treatment, and these events were unaffected by tau expression. Although transient coexpression of CDK5 and its activator, p25, increased CDK5 activity greater than tenfold, increases in caspase-3 activity in response to thapsigargin treatment were unaffected by the presence of CDK5/p25. Tau phosphorylation at the PHF-1 epitope, but not the Tau-1 epitope, was increased significantly in CDK5/p25-transfected cells compared to cells transfected with dominant negative CDK5 (DNCDK5). The PHF-1 epitope remained phosphorylated until 48 hr after thapsigargin treatment in the CDK5/p25-transfected cells. Over the course of apoptosis in this model, phosphorylation of the Tau-1 epitope was unaffected in cells transfected with DNCDK5, vector, or CDK5/p25. In summary, these results demonstrate that CDK5 does not have a significant impact on tau phosphorylation and thapsigargin-induced apoptosis in this neuronal cell model.