JIP1-Mediated JNK Activation Negatively Regulates Synaptic Plasticity and Spatial Memory

The c-Jun N-terminal kinase (JNK) signal transduction pathway is implicated in learning and memory. Here, we examined the role of JNK activation mediated by the JIP1 scaffold protein. We compared male wild-type mice with a mouse model harboring a point mutation in the Jip1 gene that selectively blocks JIP1-mediated JNK activation. These male mutant mice exhibited increased NMDA receptor currents, increased NMDA receptor-mediated gene expression, and a lower threshold for induction of hippocampal long-term potentiation. The JIP1 mutant mice also displayed improved hippocampus-dependent spatial memory and enhanced associative fear conditioning. These results were confirmed using a second JIP1 mutant mouse model that suppresses JNK activity. Together, these observations establish that JIP1-mediated JNK activation contributes to the regulation of hippocampus-dependent, NMDA receptor-mediated synaptic plasticity and learning. SIGNIFICANCE STATEMENT: The results of this study demonstrate that JNK activation induced by the JIP1 scaffold protein negatively regulates the threshold for induction of long-term synaptic plasticity through the NMDA-type glutamate receptor. This change in plasticity threshold influences learning. Indeed, mice with defects in JIP1-mediated JNK activation display enhanced memory in hippocampus-dependent tasks, such as contextual fear conditioning and Morris water maze, indicating that JIP1-JNK constrains spatial memory. This study reports the identification of JIP1-mediated JNK activation as a novel molecular pathway that negatively regulates NMDA receptor-dependent synaptic plasticity and memory

The Impact of Selenium Deficiency on Cardiovascular Function

Selenium (Se) is an essential trace element that is necessary for various metabolic processes, including protection against oxidative stress, and proper cardiovascular function. The role of Se in cardiovascular health is generally agreed upon to be essential yet not much has been defined in terms of specific functions. Se deficiency was first associated with Keshan’s Disease, an endemic disease characterized by cardiomyopathy and heart failure. Since then, Se deficiency has been associated with multiple cardiovascular diseases, including myocardial infarction, heart failure, coronary heart disease, and atherosclerosis. Se, through its incorporation into selenoproteins, is vital to maintain optimal cardiovascular health, as selenoproteins are involved in numerous crucial processes, including oxidative stress, redox regulation, thyroid hormone metabolism, and calcium flux, and inadequate Se may disrupt these processes. The present review aims to highlight the importance of Se in cardiovascular health, provide updated information on specific selenoproteins that are prominent for proper cardiovascular function, including how these proteins interact with microRNAs, and discuss the possibility of Se as a potential complemental therapy for prevention or treatment of cardiovascular disease

27. The impact of introduction of code-stemi program on clinical outcomes of acute st-elevation myocardial infarction (stemi) patients undergoing primary pci: Single center study in Saudi Arabia

This study was conducted to evaluate the effect of direct Emergency Department activation of the Catheterization Lab on door to balloon (D2B) time and outcomes of acute ST-elevation myocardial infarction (STEMI) patients in King Khalid University Hospital (KKUH). Establishing dedicated comprehensive STEMI programs aiming at reducing door to balloon time will impact favourably the outcomes of patients presenting with acute STEMI. This was a retrospective cohort study that involved 100 patients in KKUH who presented with acute STEMI and underwent primary percutaneous intervention (PPCI), between June 2010 and January 2015. The cohort was divided into two groups, the first group consisted of 50 patients who were treated before establishing the Code-STEMI protocol, whereas the second group were 50 patients who were treated according to the protocol, which was implemented in June 2013. Code-STEMI program is a comprehensive program that includes direct activation of the cath lab team using a single call system, data monitoring and feedback, and standardized order forms. The mean age in both groups was 54 ± 12 years and 86% (43) and 94% (47) of the patients in the two groups were males, respectively. 90% (90) of patients in both groups had one or more comorbidities.Code-STEMI group had a significantly lower D2BT with 70% of patients treated within the recommended 90 minutes (median = 76.5 min, IQR: 63–90 min) compared to only 26% of pre code-STEMI patients (median = 107 min, IQR: 74–149 min) In-hospital complications were lower in the Code-STEMI group; however, the only statistically significant reduction was in non-fatal re-infarction, (8% vs. 0%, p = 0.043). In addition, the number of patients with more than one in-hospital complications was also reduced by 20%.Implementation of direct ER-Catheterization lab activation protocol was associated with a significant reduction in D2B time, and an overall improvement of in-hospital outcomes