14 research outputs found
Reduced cAMP, Akt Activation and p65-c-Rel Dimerization: Mechanisms Involved in the Protective Effects of mGluR3 Agonists in Cultured Astrocytes
In recent decades, astrocytes have emerged as key pieces in the maintenance of normal functioning of the central nervous system. Any impairment in astroglial function can ultimately lead to generalized disturbance in the brain, thus pharmacological targets associated with prevention of astrocyte death are actually promising. Subtype 3 of metabotropic glutamate receptors (mGluR3) is present in astrocytes, its activation exerting neuroprotective roles. In fact, we have previously demonstrated that mGluR3 selective agonists prevent nitric oxide (NO)-induced astrocyte death. However, mechanisms responsible for that cytoprotective property are still subject to study. Although inhibition of adenylyl cyclase by mGluR3 activation was extensively reported, the involvement of reduced cAMP levels in the effects of mGluR3 agonists and the association between cAMP decrease and the downstream pathways activated by mGluR3 remain neglected. Thus, we studied intracellular signaling mediating anti-apoptotic actions of mGluR3 in cultured rat astrocytes exposed to NO. In the present work, we showed that the cytoprotective effect of mGluR3 agonists (LY379268 and LY404039) requires both the reduction of intracellular cAMP levels and activation of Akt, as assessed by MTT and TUNEL techniques. Moreover, dibutyryl-cAMP impairs Akt phosphorylation induced by LY404039, indicating a relationship between mGluR3-reduced cAMP levels and PI3K/Akt pathway activation. We also demonstrated, by co-immunoprecipitation followed by western-blot, that the mGluR3 agonists not only induce per se survival-linked interaction between members of the NF-ÎşB family p65 and c-Rel, but also impede reduction of levels of p65-c-Rel dimers caused by NO, suggesting a possible anti-apoptotic role for p65-c-Rel. All together, these data suggest that mGluR3 agonists may regulate cAMP/Akt/p65-c-Rel pathway, which would contribute to the protective effect of mGluR3 against NO challenge in astrocytes. Our results widen the knowledge about mechanisms of action of mGluR3, potential targets for the treatment of neurodegenerative disorders where a pathophysiological role for NO has been established
The role of researchers in disseminating evidence to public health practice settings: a cross-sectional study
Inequalities in the provision of paediatric speech and language therapy services across London boroughs
Amyloid-β and Alzheimer’s disease type pathology differentially affects the calcium signalling toolkit in astrocytes from different brain regions
Phosphorylation of Connexin 43 by Cdk5 Modulates Neuronal Migration During Embryonic Brain Development
Perisynaptic astroglial processes: dynamic processors of neuronal information
International audienceNeuroglial interactions are now recognized as essential to brain functions. Extensive research has sought to understand the modalities of such dialog by focusing on astrocytes, the most abundant glial cell type of the central nervous system. Neuron-astrocyte exchanges occur at multiple levels, at different cellular locations. With regard to information processing, regulations occurring around synapses are of particular interest as synaptic networks are thought to underlie higher brain functions. Astrocytes morphology is tremendously complex in that their processes exceedingly branch out to eventually form multitudinous fine leaflets. The latter extremities have been shown to surround many synapses, forming perisynaptic astrocytic processes, which although recognized as essential to synaptic functioning, are poorly defined elements due to their tiny size. The current review sums up the current knowledge on their molecular and structural properties as well as the functional characteristics making them good candidates for information processing units