Search results for "Connexins"
showing 10 items of 37 documents
From non-excitable single-cell to multicellular bioelectrical states supported by ion channels and gap junction proteins: Electrical potentials as di…
2019
Endogenous bioelectric patterns within tissues are an important driver of morphogenesis and a tractable component of a number of disease states. Developing system-level understanding of the dynamics by which non-neural bioelectric circuits regulate complex downstream cascades is a key step towards both, an evolutionary understanding of ion channel genes, and novel strategies in regenerative medicine. An important capability gap is deriving rational modulation strategies targeting individual cells' bioelectric states to achieve global (tissue- or organ-level) outcomes. Here, we develop an ion channel-based model that describes multicellular states on the basis of spatio-temporal patterns of …
Epidemiological study of nonsyndromic hearing loss in Sicilian newborns
2007
Deafness is caused by a variety of facts, genetic and environmental. Regarding the acquired causes, deafness can be the consequence of prenatal infections, acoustic or cerebral trauma, and the use of ototoxic drugs. Deafness can be the only manifestation (nonsyndromic forms) or it may occur together with other phenotypic findings (syndromic forms). The majority of nonsyndromicdeafness has a genetic basis [Van Camp et al., 1997]. In recent years, deafness and hearing loss have assumed a clinical importance in the study of congenital disorders [Morton et al., 1991]. The clinical interest for hearing loss is supported by the social impact that this disorder has; if not treated, delays in the d…
Cyclic adenosine monophosphate is a key component of regulatory T cell–mediated suppression
2007
Naturally occurring regulatory T cells (T reg cells) are a thymus-derived subset of T cells, which are crucial for the maintenance of peripheral tolerance by controlling potentially autoreactive T cells. However, the underlying molecular mechanisms of this strictly cell contact–dependent process are still elusive. Here we show that naturally occurring T reg cells harbor high levels of cyclic adenosine monophosphate (cAMP). This second messenger is known to be a potent inhibitor of proliferation and interleukin 2 synthesis in T cells. Upon coactivation with naturally occurring T reg cells the cAMP content of responder T cells is also strongly increased. Furthermore, we demonstrate that natur…
Active acetylcholine receptors prevent the atrophy of skeletal muscles and favor reinnervation
2020
Denervation of skeletal muscles induces severe muscle atrophy, which is preceded by cellular alterations such as increased plasma membrane permeability, reduced resting membrane potential and accelerated protein catabolism. The factors that induce these changes remain unknown. Conversely, functional recovery following denervation depends on successful reinnervation. Here, we show that activation of nicotinic acetylcholine receptors (nAChRs) by quantal release of acetylcholine (ACh) from motoneurons is sufficient to prevent changes induced by denervation. Using in vitro assays, ACh and non-hydrolysable ACh analogs repressed the expression of connexin43 and connexin45 hemichannels, which prom…
Connexin-30 mRNA Is Up-Regulated in Astrocytes and Expressed in Apoptotic Neuronal Cells of Rat Brain Following Kainate-Induced Seizures
2002
Glial connexins (Cxs) make an extensively interconnected functional syncytium created by a network of gap junctions between astrocytes and oligodendrocytes. Among Cxs expressed in the brain, Cx30 is expressed in grey matter astrocytes, as shown at the protein level by immunoistochemistry. In the present study we aimed to perform a detailed study of the regional distribution of Cx30 mRNA in the adult and postnatal developing rat brain, analyzing its expression by in situ hybridization, and determining its cell type localization by double labeling. Recently, it has been suggested that neuronal activity may control the level of intercellular communication between astrocytes through gap junctio…
Cellular expression of connexins in the rat brain: neuronal localization, effects of kainate-induced seizures and expression in apoptotic neuronal ce…
2003
The identification of connexins (Cxs) expressed in neuronal cells represents a crucial step for understanding the direct communication between neurons and between neuron and glia. In the present work, using a double-labelling method combining in situ hybridization for Cx mRNAs with immunohistochemical detection for neuronal markers, we provide evidence that, among cerebral connexins (Cx26, Cx32, Cx36, Cx37, Cx40, Cx43, Cx45 and Cx47), only Cx45 and Cx36 mRNAs are localized in neuronal cells in both developing and adult rat brain. In order to establish whether connexin expression is influenced in vivo by abnormal neuronal activity, we examined the short-term effects of kainate-induced seizur…
Anticonvulsant effects of carbenoxolone in genetically epilepsy prone rats (GEPRs).
2004
Carbenoxolone (CBX), the succinyl ester of glycyrrhetinic acid, is an inhibitor of gap junctional intercellular communication. Systemic administration of CBX was able to decrease the seizure severity score and to increase the latency time of seizure onset in genetically epilepsy prone rats (GEPRs). In particular, intravenous or intraperitoneal administration of carbenoxolone (5-30 mg/kg) produced a dose-dependent and significant reduction in the clonic and tonic phases of the audiogenic seizures in GEPRs. The anticonvulsant doses were not associated with an impairment of motor coordination. The bilateral microinjection of CBX (0.001-0.50 microg/0.5 microl) into the inferior colliculi, the s…
Expression of connexin36 in the adult and developing rat brain.
2000
The distribution of connexin36 (Cx36) in the adult rat brain and retina has been analysed at the protein (immunofluorescence) and mRNA (in situ hybridization) level. Cx36 immunoreactivity, consisting primarily of round or elongated puncta, is highly enriched in specific brain regions (inferior olive and the olfactory bulb), in the retina, in the anterior pituitary and in the pineal gland, in agreement with the high levels of Cx36 mRNA in the same regions. A lower density of immunoreactive puncta can be observed in several brain regions, where only scattered subpopulations of cells express Cx36 mRNA. By combining in situ hybridization for Cx36 mRNA with immunohistochemistry for a general neu…
Deficient membrane integration of the novel p.N14D-GJB2mutant associated with non-syndromic hearing impairment
2006
Mutations in GJB2, the gene encoding for the Gap Junction protein Connexin 26 (Cx26), have been established as the major cause of hereditary, non-syndromic hearing impairment (HI). We report here the identification of a novel point mutation in GJB2, c.40A>G [p.N14D], detected in compound heterozygosity with the c.35delG mutation in two brothers with moderate non-syndromic sensorineural HI. The mother who carried one wildtype and a p.N14D allele displayed normal hearing. The mutation leads to substitution of the neutral amino acid asparagine (N) by the negatively charged aspartic acid (D) at amino acid number 14, a position that is conserved among Cx26 of different organisms and among many o…
Mild Aerobic Exercise Training Hardly Affects the Diaphragm of mdx Mice
2016
In the mdx mice model of Duchenne Muscular Dystrophy (DMD), mild endurance exercise training positively affected limb skeletal muscles, whereas few and controversial data exist on the effects of training on the diaphragm. The diaphragm was examined in mdx (C57BL/10ScSn-Dmdmdx) and wild-type (WT, C57BL/10ScSc) mice under sedentary conditions (mdx-SD, WT-SD) and during mild exercise training (mdx-EX, WT-EX). At baseline, and after 30 and 45 days (training: 5 d/wk for 6 weeks), diaphragm muscle morphology and Cx39 protein were assessed. In addition, tissue levels of the chaperonins Hsp60 and Hsp70 and the p65 subunit of nuclear factor-kB (NF-kB) were measured in diaphragm, gastrocnemius, and q…