The serine hydrolase α/β-hydrolase domain 6 (ABHD6) hydrolyzes the most abundant endocannabinoid (eCB) in the brain, 2-arachidonoylglycerol (2-AG), and controls its availability at cannabinoid receptors. We show that ABHD6 inhibition decreases pentylenetetrazole (PTZ)-induced generalized tonic-clonic and myoclonic seizure incidence, and severity. This effect is retained in cnr1−/− or cnr2−/− mice, but blocked by addition of a subconvulsive dose of picrotoxin, suggesting the involvement of GABAA receptors. ABHD6 inhibition also blocked spontaneous seizures in R6/2 mice, a genetic model of Juvenile Huntington’s disease known to exhibit dysregulated eCB signaling. ABHD6 blockade retained its antiepileptic activity over chronic dosing and was not associated with psychomotor or cognitive effects. While the etiology of seizures in R6/2 mice remains unsolved, involvement of the hippocampus is suggested by interictal epileptic discharges, increased expression of vGLUT1 but not vGAT, and reduced Neuropeptide Y (NPY) expression. We conclude that ABHD6 inhibition may represent a novel antiepileptic strategy.
Background and method Pretrial detention makes up 75% of juvenile detention admissions and contributes to the disproportionate contact of minoritized youth in the juvenile carceral system. Given that prior evidence largely examines differences between Black and white youth, this study expands research on disproportionate contact in the pretrial detention setting to Hispanic/Latinx, Indigenous, and Asian youth. With a sample of over 44,000 juvenile cases in a northwest state, we used a generalized linear mixed model to estimate the effect of individual level characteristics while accounting for the random effect of differences at the county level. Additionally, we utilized Critical Race Theory (CRT) in formulating our theoretical model and predictions and apply CRT in our analysis and discussion of our results. In doing so we hope to build upon its application in public health discourse for naming and deconstructing processes that lead to unjust social and health stratification. Results After factoring in gender, age, crime severity, previous offenses, and variation between counties, our analyses show that Black, Hispanic/Latinx, and American Indian/Alaskan Native youth are more likely to experience pretrial detention than white youth. The likelihood of pretrial detention for Asian youth and for youth identified as “Other” or “Unknown” was not significantly different from white youth. Conclusions As the iatrogenic effects of detention are disproportionately imposed upon youth of color—particularly Black, Indigenous, and Hispanic/Latinx youth—the disparities present in our study reveal further evidence of institutional racism. In this way, we can see how this carceral process operates as a mechanism of racialized social stratification as put forth by CRT. Considering implications for policy or further research, persistent disparity highlights an enduring need for building or strengthening diversion programs and alternatives to the carceral system, with emphasis on those that are culturally responsive.
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