Synapsin I Synchronizes GABA Release in Distinct Interneuron Subpopulations.

Neurotransmitters can be released either synchronously or asynchronously with respect to action potential timing. Synapsins (Syns) are a family of synaptic vesicle (SV) phosphoproteins that assist gamma-aminobutyric acid (GABA) release and allow a physiological excitation/inhibition balance. Consistently, deletion of either or both Syn1 and Syn2 genes is epileptogenic. In this work, we have characterized the effect of SynI knockout (KO) in the regulation of GABA release dynamics. Using patch-clamp recordings in hippocampal slices, we demonstrate that the lack of SynI impairs synchronous GABA release via a reduction of the readily releasable SVs and, in parallel, increases asynchronous GABA release. The effects of SynI deletion on synchronous GABA release were occluded by ω-AgatoxinIVA, indicating the involvement of P/Q-type Ca2+channel-expressing neurons. Using in situ hybridization, we show that SynI is more expressed in parvalbumin (PV) interneurons, characterized by synchronous release, than in cholecystokinin or SOM interneurons, characterized by a more asynchronous release. Optogenetic activation of PV and SOM interneurons revealed a specific reduction of synchronous release in PV/SynIKO interneurons associated with an increased asynchronous release in SOM/SynIKO interneurons. The results demonstrate that SynI is differentially expressed in interneuron subpopulations, where it boosts synchronous and limits asynchronous GABA release.

The high expression of p53 in sporadic colorectal carcinoma is associated with metastasis and decreased survival.

INTRODUCTION: Alteration in the p53 tumour suppressor gene is an event that occurs frequently in human cancer, although its role as predictive and/or prognostic marker is still unclear. The aim of this study was to compare the expression profiles of p53 in colorectal carcinoma with clinicopathological features and survival rate at 5 years from diagnosis. METHODS: One hundred and twenty cases of primary sporadic colorectal cancers (CRCs) and 80 matched normal mucosas were analyzed by immunohistochemistry on paraffin-embedded specimens. The correlation between protein expression profiles, clinicopathological parameters and survival was investigated. RESULTS: In tumour tissues, the expression of p53 was high in 41 cases, low in 38 and negative in 41. A significant correlation was observed between increased p53 expression presence of lymph node (p = 0.002) or liver metastasis (p = 0.008). Moreover, higher levels of p53 were related with advanced tumour stage (III-IV; p = 0.007), poor survival and disease recurrence (p < 0.01). Interestingly, in multivariate analysis p53 expression and distant metastasis were independent prognostic markers. DISCUSSION: Our results suggest that nuclear p53 accumulation in sporadic CRC may have prognostic significance and contribute to identification of patients at high risk of mortality. The current findings may be relevant for management of patients with CRC.

The influence of in vivo pretreatment of cyclophosphamide on phagocytic activity of mouse macrophages in vitro.

The action of cyclophosphamide on phagocytosis by macrophages from mouse peritoneal exudate cultured in vitro was studied. The mice were pretreated with cyclophosphamide administered for seven days. The experiments were carried out in the presence of serum (with or without complement) from untreated animals or without serum. A significantly increased phagocytic activity was shown in experiments without serum and when decomplemented serum was used. No significant variation was found when macrophages from treated mice were tested with serum with complement from untreated animals. It is tentatively assumed that low dosage administration in vivo of cyclophosphamide does not affect macrophage phagocytic activity while several findings suggest an inhibitory effect of cyclophosphamide on T and B lymphocytes.

Effect of pretreatment with prednisolone on the phagocytic activity of mouse peritoneal macrophages in vitro.

The phagocytic activity on in vitro cultured mouse peritoneal macrophages derived from animals treated with 6-alpha-methyl-prednisolone was examined. The statistical evaluation of results showed an increase of phagocytic activity of macrophages derived from treated animals in comparison with controls.