Glutamate corelease promotes growth and survival of midbrain dopamine neurons.

Recent studies have proposed that glutamate corelease by mesostriatal dopamine (DA) neurons regulates behavioral activation by psychostimulants. How and when glutamate release by DA neurons might play this role remains unclear. Considering evidence for early expression of the type 2 vesicular glutamate transporter in mesencephalic DA neurons, we hypothesized that this cophenotype is particularly important during development. Using a conditional gene knock-out approach to selectively disrupt the Vglut2 gene in mouse DA neurons, we obtained in vitro and in vivo evidence for reduced growth and survival of mesencephalic DA neurons, associated with a decrease in the density of DA innervation in the nucleus accumbens, reduced activity-dependent DA release, and impaired motor behavior. These findings provide strong evidence for a functional role of the glutamatergic cophenotype in the development of mesencephalic DA neurons, opening new perspectives into the pathophysiology of neurodegenerative disorders involving the mesostriatal DA system.

COVID-19 and Sickle Cell Disease in the Province of Quebec, Canada: Outcomes after Two Years of the Pandemic.

BACKGROUND: Patients with sickle cell disease (SCD) are considered at higher risk of severe COVID-19 infection. However, morbidity and mortality rates are variable among countries. To date, there are no published reports that document outcomes of SCD patients with COVID-19 in Canada. METHODS: A web-based registry was implemented in June 2020 capturing outcomes of SCD patients with COVID-19 from March 2020 to April 2022 and comparing them to the general population of Quebec, Canada. RESULTS: After 24 months of the pandemic, 185 SCD patients with confirmed SARS-CoV-2 infection were included in the registry. Overall, the population was young (median age 12 years old) and had few comorbidities. No deaths were reported. Risk of hospitalization and admission to intensive care unit (ICU) because of COVID-19 was higher in patients with SCD than in the general population (relative risks (RR) 5.15 (95% confidence interval (95% CI) 3.84-6.91), p ˂ 0.001 and 4.56 (95% CI 2.09-9.93) p ˂ 0.001). A history of arterial hypertension or acute chest syndrome in the past 12 months was associated with a higher risk of severe disease (RR = 3.06 (95% CI 1.85-5.06) p = 0.008 and 2.27 (95% CI 1.35-3.83) p = 0.01). Hospitalized patients had lower hemoglobin F than non-hospitalized patients (12% vs. 17%, p = 0.02). For those who had access to vaccination at the time of infection, 25 out of 26 patients were adequately vaccinated and had mild disease. CONCLUSIONS: The SCD population is at higher risk of severe disease than the general population. However, we report favorable outcomes as no deaths occurred. Registries will continue to be critical to document the impact of novel COVID-19 specific therapy and vaccines for the SCD population.