1Glia 2015 Jun -1: -1
TitlePrenatal exposure to inflammatory conditions increases Cx43 and Panx1 unopposed channel opening and activation of astrocytes in the offspring effect on neuronal survival.
AbstractSeveral epidemiological studies indicate that children born from mothers exposed to infections during gestation, have an increased risk to develop neurological disorders, including schizophrenia, autism and cerebral palsy. Given that it is unknown if astrocytes and their crosstalk with neurons participate in the above mentioned brain pathologies, the aim of this work was to address if astroglial paracrine signaling mediated by Cx43 and PANX1 unopposed channels could be affected in the offspring of LPS-exposed dams during pregnancy. Ethidium uptake experiments showed that prenatal LPS-exposure increases the activity of astroglial Cx43 and PANX1 unopposed channels in the offspring. Induction of unopposed channel opening by prenatal LPS exposure depended on intracellular Ca(2+) levels, cytokine production and activation of p38 MAP kinase/iNOS pathway. Biochemical assays and Fura-2AM/DAF-FM time-lapse fluorescence images revealed that astrocytes from the offspring of LPS-exposed dams displayed increased spontaneous Ca(2+) dynamics and NO production, whereas iNOS levels and release of IL-1?/TNF-? were also increased. Interestingly, we found that prenatal LPS exposure enhanced the release of ATP through astroglial Cx43 and PANX1 unopposed channels in the offspring, resulting in an increased neuronal death mediated by the activation of neuronal P2X7 receptors and PANX1 channels. Altogether, this evidence suggests that astroglial Cx43 and PANX1 unopposed channel opening induced by prenatal LPS exposure depended on the inflammatory activation profile and the activation pattern of astrocytes. The understanding of the mechanism underlying astrocyte-neuron crosstalk could contribute to the development of new strategies to ameliorate the brain abnormalities induced in the offspring by prenatal inflammation. GLIA 2015.
SCZ Keywordsschizophrenia
2Eur Arch Psychiatry Clin Neurosci 2015 Jul -1: -1
TitleThe role of Pannexin gene variants in schizophrenia: systematic analysis of phenotypes.
AbstractPannexins are a group of brain-expressed channel proteins thought to be regulators of schizophrenia-linked pathways including glutamate release, synaptic plasticity and neural stem proliferation. We got evidence for linkage of a catatonic phenotype to the PANX2 locus in a family study. Aim of our study was to evaluate the role of Pannexins in schizophrenia and clinical phenotypes, particularly with regard to periodic catatonia. We genotyped six single-nucleotide polymorphisms at PANX1, five at PANX2 and three at PANX3 in 1173 German cases with schizophrenia according to DSM-5 and 480 controls. Our sample included 338 cases with periodic catatonia corresponding to Leonhard's classification. Association with schizophrenia according to DSM-5 was limited to genotype rs4838858-TT [p = 0.02, odds ratio (OR) 3.1] and haplotype rs4838858T-rs5771206G (p = 0.02, OR 2.7) at PANX2. We found no significant association with clinical phenotypes. Our limited findings do not support a major contribution of PANX1-3 to disease risk of schizophrenia according to DSM-5. We cannot confirm an association of the PANX2 loci at chromosome 22q13 with periodic catatonia.
SCZ Keywordsschizophrenia