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Summary It has been suggested that aberrant activation of glycogen synthase kinase-3-beta (GSK-3β) can trigger abnormal tau hyperphosphorylation and aggregation, which ultimately leads to neuronal/synaptic damage and impaired cognition in Alzheimer disease (AD). We examined if isoform-selective partial reduction of GSK-3β can decrease pathological tau changes, including hyperphosphorylation, aggregation, and spreading, in mice with localized human wild-type tau (hTau) expression in the brain. We used adeno-associated viruses (AAVs) to express hTau locally in the entorhinal cortex of wild-type and GSK-3β hemi-knockout (GSK-3β-HK) mice. GSK-3β-HK mice had significantly less accumulation of hyperphosphorylated tau in synapses and showed a significant decrease of tau protein spread between neurons. In primary neuronal cultures from GSK-3β-HK mice, the aggregation of exogenous FTD-mutant tau was also significantly reduced. These results show that a partial decrease of GSK-3β significantly represses tau-initiated neurodegenerative changes in the brain, and therefore is a promising therapeutic target for AD and other tauopathies.

Objectives Some states, including Massachusetts, require automatic filing of child abuse and neglect for substance-exposed newborns, including infants exposed in-utero to clinician-prescribed medications to treat opioid use disorder (MOUD). The aim of this article is to explore effects of these mandated reporting policies on pregnant and postpartum people receiving MOUD. Methods We used modified grounded research theory, literature findings, and constant comparative methods to extract, analyze and contextualize perinatal experiences with child protection systems (CPS) and explore the impact of the Massachusetts mandated reporting policy on healthcare experiences and OUD treatment decisions. We drew from 26 semi-structured interviews originally conducted within a parent study of perinatal MOUD use in pregnancy and the postpartum period. Results Three themes unique to CPS reporting policies and involvement emerged. First, mothers who received MOUD during pregnancy identified mandated reporting for prenatally prescribed medication utilization as unjust and stigmatizing. Second, the stress caused by an impending CPS filing at delivery and the realities of CPS surveillance and involvement after filing were both perceived as harmful to family health and wellbeing. Finally, pregnant and postpartum individuals with OUD felt pressure to make medical decisions in a complex environment in which medical recommendations and the requirements of CPS agencies often compete. Conclusions for Practice Uncoupling of OUD treatment decisions in the perinatal period from mandated CPS reporting at time of delivery is essential. The primary focus for families affected by OUD must shift from surveillance and stigma to evidence-based treatment and access to supportive services and resources.