Prophylactic treatment with the c-Abl inhibitor, neurotinib, diminishes neuronal damage and the convulsive state in pilocarpine-induced mice.

The molecular mechanisms underlying seizure generation remain elusive, yet they are crucial for developing effective treatments for epilepsy. The current study shows that inhibiting c-Abl tyrosine kinase prevents apoptosis, reduces dendritic spine loss, and maintains N-methyl-d-aspartate (NMDA) receptor subunit 2B (NR2B) phosphorylated in in vitro models of excitotoxicity. Pilocarpine-induced status epilepticus (SE) in mice promotes c-Abl phosphorylation, and disrupting c-Abl activity leads to fewer seizures, increases latency toward SE, and improved animal survival. Currently, clinically used c-Abl inhibitors are non-selective and have poor brain penetration. The allosteric c-Abl inhibitor, neurotinib, used here has favorable potency, selectivity, pharmacokinetics, and vastly improved brain penetration. Neurotinib-administered mice have fewer seizures and improved survival following pilocarpine-SE induction. Our findings reveal c-Abl kinase activation as a key factor in ictogenesis and highlight the impact of its inhibition in preventing the insurgence of epileptic-like seizures in rodents and humans.

[National health services system entrance contest for specialties in Chile. Quotas and scores obtained by applicants]. / Puntaje total, calificación médica nacional y cupos según programa de especialidad en el Concurso de Ingreso al Sistema Nacional de Servicios de Salud. Período 2017-2019.

Among the several programs that allow access to medical specialization in Chile, the National Health Services System Entrance Contest (CONISS) is held annually for newly graduated physicians, which has a high number of applicants. The academic qualifications expressed as National Medical Qualification (CMN) are the main item of the scoring system. We reviewed the total scores and the CMN of the different medical specialization programs that exist in the country, which constitutes novel and relevant information for future medical graduates interested in applying to the program. In addition, the quotas of the different programs are reported, expressed as total, free, and used quotas.

Puntaje total, calificación médica nacional y cupos según programa de especialidad en el Concurso de Ingreso al Sistema Nacional de Servicios de Salud. Período 2017-2019 / National health services system entrance contest for specialties in Chile. Quotas and scores obtained by applicants

Among the several programs that allow access to medical specialization in Chile, the National Health Services System Entrance Contest (CONISS) is held annually for newly graduated physicians, which has a high number of applicants. The academic qualifications expressed as National Medical Qualification (CMN) are the main item of the scoring system. We reviewed the total scores and the CMN of the different medical specialization programs that exist in the country, which constitutes novel and relevant information for future medical graduates interested in applying to the program. In addition, the quotas of the different programs are reported, expressed as total, free, and used quotas.

Dopamine receptor D5 deficiency results in a selective reduction of hippocampal NMDA receptor subunit NR2B expression and impaired memory.

Pharmacological evidence associates type I dopamine receptors, including subtypes D1 and D5, with learning and memory. Analyses using genetic approaches have determined the relative contribution of dopamine receptor D1 (D1R) in cognitive tasks. However, the lack of drugs that can discriminate between D1R and D5R has made the pharmacological distinction between the two receptors difficult. Here, we aimed to determine the role of D5R in learning and memory. In this study we tested D5R knockout mice and wild-type littermates in a battery of behavioral tests, including memory, attention, locomotion, anxiety and motivational evaluations. Our results show that genetic deficiency of D5R significantly impairs performance in the Morris water maze paradigm, object location and object recognition memory, indicating a relevant role for D5R in spatial memory and recognition memory. Moreover, the lack of D5R resulted in decreased exploration and locomotion. In contrast, D5R deficiency had no impact on working memory, anxiety and depressive-like behavior, measured using the spontaneous alternation, open-field, tail suspension test, and forced swimming test. Electrophysiological analyses performed on hippocampal slices showed impairment in long-term-potentiation in mice lacking D5R. Further analyses at the molecular level showed that genetic deficiency of D5R results in a strong and selective reduction in the expression of the NMDA receptor subunit NR2B in the hippocampus. These findings demonstrate the relevant contribution of D5R in memory and suggest a functional interaction of D5R with hippocampal glutamatergic pathways.