Activation of the PI3K/AKT/mTOR Pathway in Cajal-Retzius Cells Leads to Their Survival and Increases Susceptibility to Kainate-Induced Seizures.

Cajal-Retzius cells (CRs) are a class of transient neurons in the mammalian cortex that play a critical role in cortical development. Neocortical CRs undergo almost complete elimination in the first two postnatal weeks in rodents and the persistence of CRs during postnatal life has been detected in pathological conditions related to epilepsy. However, it is unclear whether their persistence is a cause or consequence of these diseases. To decipher the molecular mechanisms involved in CR death, we investigated the contribution of the PI3K/AKT/mTOR pathway as it plays a critical role in cell survival. We first showed that this pathway is less active in CRs after birth before massive cell death. We also explored the spatio-temporal activation of both AKT and mTOR pathways and reveal area-specific differences along both the rostro-caudal and medio-lateral axes. Next, using genetic approaches to maintain an active pathway in CRs, we found that the removal of either PTEN or TSC1, two negative regulators of the pathway, lead to differential CR survivals, with a stronger effect in the Pten model. Persistent cells in this latter mutant are still active. They express more Reelin and their persistence is associated with an increase in the duration of kainate-induced seizures in females. Altogether, we show that the decrease in PI3K/AKT/mTOR activity in CRs primes these cells to death by possibly repressing a survival pathway, with the mTORC1 branch contributing less to the phenotype.

Association study between polymorphisms in MIA3, SELE, SMAD3 and CETP genes and coronary artery disease in an Iranian population.

BACKGROUND: Coronary artery disease (CAD) is the most common heart disease. Several studies have shown association between some polymorphism in different genes with CAD. Finding this association can be used in order to early diagnosis and prevention of CAD. METHOD: 101 CAD patients with ≥ 50% luminal stenosis of any coronary vessel as case group and 111 healthy individuals as control group were selected. the polymorphisms were evaluated by ARMS-PCR and RFLP-PCR methods. RESULT: The results of this study show that there is no significant association between rs17228212, rs17465637, and rs708272 and risk of CAD. But there is significant association between risk of CAD and rs5355 (p-value = 0.022) and rs3917406 (p-value = 0.006) in total cases, and rs5882 (p-value = 0.001) in male cases. CONCLUSIONS: Our findings revealed a significant interaction between CETP SNPs and CETP activity for affecting HDL-C levels. The SELE gene is a known cell adhesion molecule with a significant role in inflammation. Studies about possible linkage between SELE gene polymorphisms and the development of CAD are conflicting. We have found a significant association between polymorphisms of SELE gene and risk of CAD.