SUMMARY The CACNA1A gene, encoding the voltage-gated calcium channel subunit α1A, is involved in pre- and postsynaptic Ca2+ signaling, gene expression, and several genetic neurological disorders. We found that CACNA1A employs a novel strategy to directly coordinate a gene expression program, using a bicistronic mRNA bearing a cryptic internal ribosomal entry site (IRES). The first cistron encodes the well-characterized α1A subunit. The second expresses a newly-recognized transcription factor, α1ACT, that coordinates expression of a program of genes involved in neural and Purkinje cell development. α1ACT also contains the polyglutamine (polyQ) tract that, when expanded, causes spinocerebellar ataxia type 6 (SCA6). When expressed as an independent polypeptide, α1ACT, bearing an expanded polyQ tract, lacks transcription factor function and neurite outgrowth properties, causes cell death in culture, and leads to ataxia and cerebellar atrophy in transgenic mice. Suppression of CACNA1A IRES function in SCA6 may be a potential therapeutic strategy.

Background and Purpose— Racial and ethnic disparities in the access to mechanical thrombectomy (MT) for treatment of acute ischemic stroke (AIS) secondary to large vessel occlusion have been previously described. The effect of recent randomized trials validating MT as an effective therapy for AIS secondary to large vessel occlusion on such disparities has not been investigated. Methods— Information on admissions for AIS to endovascular centers occurring between January 2016 and September 2018 was obtained from a national database. The number of patients receiving IV-tPA (intravenous tissue-type plasminogen activator) and MT at each institution was determined, and patient demographics were characterized according to age, sex, race/ethnicity, and insurance status. Comparisons of patients who did and did not undergo MT and between patients of different racial and ethnic backgrounds were performed. Demographic variables independently associated with the utilization of MT were identified using multivariate linear regression analysis. Results— There were 206 853 admissions to 173 endovascular centers during the time period of interest. The overall utilization of MT was 8.4%. The utilization of MT for black/Hispanic patients was lower than that among white/non-Hispanic patients (7.0% versus 9.8%; P <0.001). Black/Hispanic patients were also less likely to receive IV-tPA (16.2% versus 20.5%; P <0.001) and to be admitted to the endovascular center after transfer from a different hospital (20.0% versus 30.1%; P <0.001). On multivariate linear regression analysis, increasing institutional proportions of patients with female sex (β=−0.601; P <0.001), insurance with Medicaid or uninsured status (β=−0.153; P =0.029), and black/Hispanic race/ethnicity (β=−0.062; P =0.046) were independently associated with lower institutional utilization of MT. Conclusions— Despite the mainstream acceptance of MT for the treatment of AIS secondary to large vessel occlusion, racial and ethnic disparities in the utilization of MT persist.

We report a beneficial effect of treatment at high-volume hospitals in spite of the detrimental effects of transfer. These findings argue for the centralization of care.

Small-conductance calcium-activated K + channels (SK channels) regulate the excitability of neurons and their responsiveness to synaptic input patterns. SK channels contribute to the afterhyperpolarization (AHP) following action potential bursts, and curtail excitatory postsynaptic potentials (EPSPs) in neuronal dendrites. Here we review evidence that SK2 channels are expressed in rat cerebellar Purkinje cells during development and throughout adulthood, and play a key role in diverse cellular processes such as the regulation of the spike firing frequency and the modulation of calcium transients in dendritic spines. In Purkinje cells as well as in other types of neurons, SK2 channel plasticity seems to provide an important mechanism allowing these cells to adjust their intrinsic excitability and to alter the probabilities for the induction of synaptic learning correlates, such as long-term potentiation (LTP).

Activation of adenosine receptors in the brain reduces anxiety-like behavior in animals and humans. Because nucleoside transporters regulate adenosine levels, we used mice lacking the type 1 equilibrative nucleoside transporter (ENT1) to investigate whether ENT1 contributes to anxiety-like behavior. The ENT1 null mice spent more time in the center of an open field compared with wild-type littermates. In the elevated plus maze, ENT1 null mice entered more frequently into and spent more time exploring the open arms. The ENT1 null mice also spent more time exploring the light side of a light-dark box compared with wild-type mice. Microinjection of an ENT1-specific antagonist, nitrobenzylthioinosine (nitrobenzylmercaptopurine riboside), into the amygdala of C57BL/6J mice reduced anxiety-like behavior in the open field and elevated plus maze. These findings show that amygdala ENT1 modulates anxiety-like behavior. The ENT1 may be a drug target for the treatment of anxiety disorders.