Editorial: Cytokines as Players of Neuronal Plasticity and Sensitivity to Environment in Healthy and Pathological Brain

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The chemokine CXCL16 modulates neurotransmitter release in hippocampal CA1 area.

Chemokines have several physio-pathological roles in the brain. Among them, the modulation of synaptic contacts and neurotransmission recently emerged as crucial activities during brain development, in adulthood, upon neuroinflammation and neurodegenerative diseases. CXCL16 is a chemokine normally expressed in the brain, where it exerts neuroprotective activity against glutamate-induced damages through cross communication with astrocytes and the involvement of the adenosine receptor type 3 (A3R) and the chemokine CCL2. Here we demonstrated for the first time that CXCL16 exerts a modulatory activity on inhibitory and excitatory synaptic transmission in CA1 area. We found that CXCL16 increases the frequency of the miniature inhibitory synaptic currents (mIPSCs) and the paired-pulse ratio (PPR) of evoked IPSCs(eIPSCs), suggesting a presynaptic modulation of the probability of GABA release. In addition, CXCL16 increases the frequency of the miniature excitatory synaptic currents (mEPSCs) and reduces the PPR of evoked excitatory transmission, indicating that the chemokine also modulates and enhances the release of glutamate. These effects were not present in the A3RKO mice and in WT slices treated with minocycline, confirming the involvement of A3 receptors and introducing microglial cells as key mediators of the modulatory activity of CXCL16 on neurons

Proper measures of connectedness

The concept of connectedness has been widely used in financial applications, in particular for systemic risk detection. Despite its popularity, at the state of the art, a rigorous definition of connectedness is still missing. In this paper we propose a general definition of connectedness introducing the notion of proper measures of connectedness (PMCs). Based on the classical concept of mean introduced by Chisini, we define a family of PMCs and prove some useful properties. Further, we investigate whether the most popular measures of connectedness available in the literature are consistent with the proposed theoretical framework. We also compare different measures in terms of forecasting performances on real financial data. The empirical evidence shows the forecasting superiority of the PMCs compared to the measures that do not satisfy the theoretical properties. Moreover, the empirical results support the evidence that the PMCs can be useful to detect in advance financial bubbles, crises, and, in general, for systemic risk detection

Importance of perforating vessels in nipple-sparing mastectomy. an anatomical description

BACKGROUND: Nipple-sparing mastectomy (NSM), understood as an oncologically valid procedure, is relatively new, and is an evolution of traditional mastectomy, particularly in relation to breast-conserving surgery. The anterior perforating branches are responsible for the cutaneous vascularization of the breast skin, and their preservation is a fundamental step to avoid possible postoperative necrosis. Therefore, evaluating the potential complications of cancer-related reconstructive surgical procedures such as NSM, both the distance of the tumoral lesion from the skin and the surgical incision site should be carefully considered. The preferred site of incision corresponds to the inframammary fold or possibly the periareolar area. METHODS: We retrospectively reviewed 113 patients who underwent NSM from January 2005 to October 2012 to evaluate skin complications. The anatomical study was performed by magnetic resonance imaging of the breast. RESULTS: Only one of the 113 women who had undergone a NSM procedure had total necrosis (0.9%) and six patients had partial necrosis (5.8%) of the nipple-areola complex

Chemokine fractalkine/CX3CL1 negatively modulates active glutamatergic synapses in rat hippocampal neurons

We examined the effects of the chemokine fractalkine (CX3CL1) on EPSCs evoked by electrical stimulation of Schaffer collaterals in patch-clamped CA1 pyramidal neurons from rat hippocampal slices. Acute application of CX3CL1 caused a sustained reduction of EPSC amplitude, with partial recovery after washout. CX3CL1-induced EPSC depression is postsynaptic in nature, because paired-pulse ratio was maintained, amplitude distribution of spontaneous excitatory postsynaptic currents shifted to lower values, and whole-cell current responses to AMPA were reversibly inhibited. EPSC depression by CX3CL1 is mediated by CX3CL1 receptor (CX3CR1), because CX3CL1 was unable to influence EPSC amplitude in CA1 pyramidal neurons from CX3CR1 knock-out mice. CX3CL1-induced depression of both EPSC and AMPA current was not observed in the absence of afferent fiber stimulation or AMPA receptor activation, respectively, indicating the requirement of sustained receptor activity for its development. Findings obtained from hippocampal slices, cultured hippocampal neurons, and transfected human embryonic kidney cells indicate that a Ca2+-, cAMP-, and phosphatase-dependent process is likely to modulate CX3CL1 effects because of the following: (1) CX3CL1-induced depression was antagonized by intracellular BAPTA, 8Br-cAMP, phosphatase inhibitors, and pertussis toxin (PTX); (2) CX3CL1 inhibited forskolin-induced cAMP formation sensitive to PTX; and (3) CX3CL1 inhibited forskolin-induced Ser845 GluR1 phosphorylation, which was sensitive to PTX and dependent on Ca2+ and phosphatase activity. Together, these findings indicate that CX3CL1 negatively modulates AMPA receptor function at active glutamatergic synapses through cell-signaling pathways by influencing the balance between kinase and phosphatase activity

Electrophysiological Properties of CA1 Pyramidal Neurons along the Longitudinal Axis of the Mouse Hippocampus

Evidence for different physiological properties along the hippocampal longitudinal axis is emerging. Here, we examined the electrophysiological features of neurons at different dorso-ventral sites of the mouse CA1 hippocampal region. Cell position was defined with respect to longitudinal coordinates of each slice. We measured variations in neuronal excitability, subthreshold membrane properties and neurotransmitter responses along the longitudinal axis. We found that (i) pyramidal cells of the dorsal hippocampus (DH) were less excitable than those of the ventral hippocampus (VH). Resting Membrane Potential (RMP) was more hyperpolarized and somatic Input Resistance (Ri) was lower in DH compared to VH. (ii) The Paired-pulse ratio (PPR) of focally induced synaptic responses was systematically reduced from the DH to the VH; (iii) Long-term-potentiation was most pronounced in the DH and fell gradually in the intermediate hippocampus and in the VH; (iv) the frequency of miniature GABAergic events was higher in the VH than in the DH; (v) the PPR of evoked inhibitory post-synaptic current (IPSC) was higher in the DH than in the VH. These findings indicate an increased probability of both GABA and glutamate release and a reduced plasticity in the ventral compared to more dorsal regions of the hippocampus

Open Science - Challenges and best practices: a view from research institutes in Italy

Talk given by Stefano Bianco at MINERVA Study Visit 2021.05. organised online by Universita' Marconi Roma

Plan S - FAQ's

A report on Plan S and the cOAlition S collaboration, with particular focus on the role of repositories and green OA

Open Science for Fair and Sustainable Access to Knowledge

Talk given at SISSA Trieste