Spinocerebellar ataxia type 6 (SCA6) is a neurodegenerative disease resulting in motor coordination deficits and cerebellar pathology. Expression of brain-derived neurotrophic factor (BDNF) is reduced in postmortem tissue from SCA6 patients. Here, we show that levels of cerebellar BDNF and its receptor, tropomyosin receptor kinase B (TrkB), are reduced at an early disease stage in a mouse model of SCA6 (SCA684Q/84Q). One month of exercise elevated cerebellar BDNF expression and improved ataxia and cerebellar Purkinje cell firing rate deficits. A TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF), likewise improved motor coordination and Purkinje cell firing rate and elevated downstream Akt signaling. Prolonged 7,8-DHF administration persistently improved ataxia when treatment commenced near disease onset but was ineffective when treatment was started late. These data suggest that 7,8-DHF, which is orally bioavailable and crosses the blood-brain barrier, is a promising therapeutic for SCA6 and argue for the importance of early intervention for SCA6.

Spinocerebellar ataxia type 6 (SCA6) is a neurodegenerative disease resulting in motor coordination deficits and cerebellar pathology. Expression of brain-derived neurotrophic factor (BDNF) is reduced in several neurodegenerative diseases, including in post-mortem tissue from SCA6 patients. Here, we show that cerebellar BDNF levels are reduced at an early disease stage in a mouse model of SCA6 (SCA684Q/84Q). One month of voluntary exercise was sufficient to elevate BDNF expression, as well as rescue both motor coordination and cerebellar Purkinje cell firing rate deficits. A BDNF mimetic, 7,8- dihydroxyflavone (7,8-DHF) likewise improved motor coordination and reversed Purkinje cell firing rate deficits, suggesting that exercise acts via BDNF-TrkB signaling. Prolonged chronic 7,8-DHF administration rescued ataxia when treatment commenced near disease onset, but was ineffective when treatment was started late. These data suggest that 7,8-DHF, which is orally bioavailable and crosses the blood-brain barrier, is a promising therapeutic for SCA6 and argue for the importance of early intervention for SCA6.

A disproportionate burden of the ongoing COVID-19 pandemic is being shouldered by members of racial and ethnic minorities and socially disadvantaged communities. Structural and social determinants of health have been recognized as key contributors to the inequalities observed. Racism, a major structural determinant of health that patterns related social determinants of health, in the USA, warrants further investigation. In this perspective piece we provide an overview of the historical context of racism, followed by preliminary findings from the ongoing COVIDStory study—a cross-sectional study addressing perceptions of COVID-19 and COVID-19 research—that highlights the experiences of non-Hispanic Black and Hispanic identifying adult participants, residing in Worcester Massachusetts, during the COVID-19 pandemic. We then discuss these findings in the context of current and past research considering racism and relevant social determinants of health. Our study results suggest that racism and its residuals (residential segregation, economic insecurity, discrimination, bias, and vigilance) are modern challenges for non-Hispanic Black and Hispanic participants, and these findings are supported by the existing literature. It is our hope that this perspective piece provides additional evidence for action on structural and social determinants affecting the health of minoritized people, especially those living in Massachusetts.

The Supreme Court decision in Dobbs v. Jackson in June 2022 reversed precedent which had previously protected abortion prior to fetal viability as a universal right within the United States. This decision almost immediately led to abortion restrictions across 25 states. The resulting lack of access to abortion care for millions of pregnant people will have profound physical and mental health consequences, the full effects of which will not be realized for years to come. Approximately 1 in 5 women access abortions in the U.S. each year. These women are diverse and represent all American groups. The Supreme court decision, however, will affect populations that have and continue to be marginalized the most. Forcing pregnant individuals to carry unwanted pregnancies worsens health outcomes and mortality risk for both the perinatal individual and the offspring. The US has one of the highest maternal mortality rates and this rate is projected to increase with abortion bans. Abortion policies also interfere with appropriate medical care of pregnant people leading to less safe pregnancies for all. Beyond the physical morbidity, the psychological sequelae of carrying a forced pregnancy to term will lead to an even greater burden of maternal mental illness, exacerbating the already existing maternal mental health crisis. This perspective piece reviews the current evidence of abortion denial on women’s mental health and care. Based on the current evidence, we discuss the clinical, educational, societal, research, and policy implications of the Dobbs v. Jackson Supreme Court decision.