Exposure to prolonged controllable or uncontrollable stress affects GABAergic function in sub-regions of the hippocampus and the amygdala.

The degree of behavioral control that an individual has over a stressor can critically determine its behavioral and neurochemical outcomes. Exposure to uncontrollable stress was previously shown to have detrimental effects on behavior, whereas exposure to equivalent controllable stress prevented these negative outcomes and even improved later stress coping. As many lines of evidence show, stress exposure can have maladaptive changes on inhibitory circuitry, and these effects were largely shown in the hippocampus and amygdala. In the current study we set out to examine alterations in GABAergic activity following exposure to the prolonged two way shuttle (TWS) avoidance task, focusing on the GABA-related factors glutamate decarboxylase (GAD)65, cholecystokinin (CCK) and neuropeptide Y (NPY). As recent views of the hippocampus assume regional specificity in hippocampal function, we examined different regions in the hippocampus, as well as the basolateral amygdala (BLA). Our findings reveal similar alterations in GAD65 in BLA for both controllable and uncontrollable stress exposure, but differential alterations in GAD65 and NPY in the dorsal dentate gyrus (DG). Synaptic plasticity and inhibitory activity in the dorsal DG was further assessed by applying different stimulation protocols and measuring evoked field potentials in vivo. Our results support a role for the DG in stress processing, emphasizing its sensitivity to the nature of the stressor.

New isoforms of VEGF are translated from alternative initiation CUG codons located in its 5'UTR.

Vascular endothelial growth factor (VEGF) has a central role in normal as well as in tumor angiogenesis. As such, VEGF is subjected to multi-level regulation at the transcriptional, post-transcriptional, translational, and post-translational levels to ensure proper expression during embryogenesis and adulthood. Its mRNA contains an exceptionally long (1038 bp) 5' untranslated region (5'UTR), which has a role in transcriptional as well as translational regulation of VEGF expression. In this communication, we provide new evidence showing that an open reading frame (ORF) present in the 5'UTR encodes for new putative isoforms of VEGF due to alternative translational initiation from CUG codons. Like VEGF, the translation of the new isoforms is not sensitive to stress signals such as anoxia. Most likely, these isoforms either possess new capabilities, which are different from the activity of the classical VEGF isoforms, or affect the efficiency and capacity of translational initiation from the canonical AUG codon.