Brain injury during the last trimester to the first 1-4 years in humans is now thought to trigger an array of intellectual and emotional problems later in life, including disorders such as schizophrenia. In adult schizophrenic brains, there is a specific loss of neurons that co-express glutamic acid decarboxylase-parvalbumin (GAD67-PV). Loss of this phenotype is thought to occur in mature animals previously exposed to N-methyl-D: -aspartate receptor (NMDAR) antagonists during late gestation or at postnatal day 7 (P7). However, in similarly treated animals, we have previously shown that GAD67 and PV are unaltered in the first 24 h. To more precisely define when changes in these markers first occur, we exposed rat pups (P7 or P6-P10) to the NMDAR antagonist MK801 and at P11 co-stained brain sections for GAD67 or PV. In the cingulate cortex, we found evidence for a reduction in PV (GAD67 levels were very low to undetectable). In contrast, in the somatosensory cortex, we found that expression of GAD67 was reduced, but PV remained stable. Further, repeated but not single doses of MK801 were necessary to see such changes. Thus, depending on the region, NMDAR antagonism appears to influence expression of PV or GAD67, but not both. These observations could not have been predicted by previous studies and raise important questions as to how the GAD67-PV phenotype is lost once animals reach maturity. More importantly, such differential effects may be of great clinical importance, given that cognitive deficits are seen in children exposed to anesthetics that act by blocking the NMDAR.

Blockade of the N-methyl-D-aspartate receptor (NMDAR) in postnatal day 7 (P7) rats can promote rapid and robust induction of the pro-apoptotic marker activated caspase-3 (AC3) and loss of the GABAergic marker GAD67 at P56. Thus, we hypothesized that NMDAR blockade-induced AC3 occurs in GAD67 positive cells at P7. To test this idea, we injected P7 rat pups with vehicle or MK801 and after 8 hours (peak of AC3 induction) we examined brain sections for both AC3 and GAD67. Compared to vehicle, MK801 profoundly induced AC3 in all brain regions examined but coexpression of GAD67 in the same cells was not observed. However, in brain regions where punctate (synaptic) GAD67 was abundant (for example, layer IV of the somatosensory cortex), AC3 was robust. These data suggest that whereas somatic expression of AC3 and GAD67 may be nonoverlapping, areas that exhibit punctate GAD67 (and are high in synaptic turnover) may be more vulnerable to MK801 exposure.

People with HIV (PWH) have higher rates of tobacco use compared to their societal counterparts and are disproportionately affected by tobacco-related morbidity and mortality. A needs assessment was conducted to assess provider beliefs and opinions on tobacco treatment barriers and treatment approaches. The results highlighted a disconnect between the known importance of quitting smoking and barriers in linking patients to treatment, such as lack of patient interest and other patient issues being a higher priority. Using this assessment data, a treatment delivery approach, Proactive Outreach with Medication Opt-out for Tobacco Treatment Engagement (PrOMOTE), was devised and piloted. PrOMOTE consisted of an outpatient clinical pharmacist trained in tobacco treatment proactively contacting patients for counseling and to prescribe smoking cessation pharmacotherapy (varenicline or dual nicotine replacement therapy (NRT)) using an opt-out approach. The pilot was conducted with 10 PWH and patient reach and opt-out rates were evaluated. Of the 10 patients contacted, 7 were reached and none opted out of the pharmacotherapy prescription (varenicline = 6; NRT = 1). Providers know the importance of smoking cessation for PWH but encounter several barriers to implementing treatment. Using PrOMOTE methods to deliver tobacco treatment increased the reach and pharmacotherapy acceptance rate of PWH who smoke.

N-methyl-D-aspartate receptor blockade promotes apoptosis at postnatal day 7 (P7) and is linked to loss of glutamic acid decarboxylase 67 (GAD67) expression in older animals. To more fully appreciate this relationship we must first understand how GAD67 is regulated postnatally. Thus, the brains of P7, P14 and P21 rats were examined for expression of GAD67 protein and we found that levels of this GABAergic marker increased steadily with age, such that by P21 there was as much as a 6-fold increase compared to P7 animals and a 1.5- to 2-fold increase compared to P14 animals, depending on the region sampled. At P7, GAD67 was almost exclusively detected in puncta, with very few cell bodies displaying this marker. In contrast, at P14 and especially P21, both puncta and cell bodies were robustly labeled. Our data indicate that adult-like expression of GAD67 emerges quite late in the postnatal period.

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