Connexin26 in adult rodent central nervous system: Demonstration at astrocytic gap junctions and colocalization with connexin30 and connexin43

Nagy, J.I.; Li, Xinbo; Rempel, Jeremy; Stelmack, Gerald L.; Patel, Daywin; Staines, W.A.; Yasumura, Thomas; Rash, John E.

doi:10.1002/cne.1414

Cited by 195 publications

(224 citation statements)

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“…Most of these antibodies were obtained from Invitrogen/Zymed Laboratories (Carlsbad, CA, USA), except mouse monoclonal anti-2,'3'-cyclic nucleotide 3'- (Li et al, 1998(Li et al, , 2004Nagy et al, 2001Nagy et al, ,2003aNagy et al, ,2003b. In addition, specificity of immunofluorescence labeling with anti-Cx36 39−4200 is shown in the present report.…”

Section: Light Microscope Immunohistochemistrymentioning

confidence: 54%

“…In addition, leptomeningeal cells in control replicas were identified by their anatomical location at the surface of the brain or spinal cord, close proximity to collagen fibers, presence of tight junctions, and by abundant Cx26 in their gap junctions (Nagy and Dermietzel, 2000;Mercier and Hatton, 2001;Nagy et al, 2001;Nagy et al, 2004).…”

Section: Identification Of Neurons Vs Glia In Freeze-fracture Replicasmentioning

confidence: 99%

“…In addition to coupling between LC neurons, recent studies (Alvarez-Maubecin et al, 2000;Van Bockstaele et al, 2004) suggested widespread but weak gap junctional coupling between LC neurons and astrocytes in neonatal and adult rats, including strong dye-transfer from astrocytes to some neurons. Using silver-intensified immunogold-labeling electron microscopic immunocytochemistry, they described detection of connexin32 (Cx32) and connexin26 (Cx26) protein in a very high percentage of dendro-dendritic profiles and proposed even greater abundance of these two connexins at membrane appositions between dendrites and glial cells (primarily astrocytes).While clear evidence exists for coupling between neurons in developing LC, several challenging issues remain concerning documentation of gap junctional coupling in this nucleus: 1) No ultrastructural data exist for the presence of connexin-containing membrane appositions between neurons in the LC that meet accepted criteria for designation as gap junctions (Brightman and Reese, 1969;Sotelo and Korn, 1978;Rash et al, 1998); 2) Unlike the reported expression of abundant Cx26 and Cx32 in both neurons and astrocytes in LC, all other locations in the CNS examined by freeze-fracture replica immunolabeling (FRIL) electron microscopy have revealed cell-type-specific expression of connexin proteins, with Cx32 found only in gap junctions formed by oligodendrocytes (Rash et al, 2001a;Nagy et al, 2003a;Li et al, 2004a;Kamasawa et al, 2005), Cx26 only in gap junctions formed by pia mater and by subpopulations of astrocytes [(Nagy et al, 2001[(Nagy et al, ,2003bRash et al, 2001a); also see Mercier and Hatton (2001) and Altevogt et al, (2004)], and Cx36 only in neuronal gap junctions (Rash et al, ,2001bKamasawa et al, 2006) [also see Fukuda et al (2006)]; 3) Although proposals for coupling of neurons to astrocytes based on propagation of "calcium waves" (Nedergaard, 1994) were extended to dye coupling between astrocytes and neurons in LC slice preparations (Alvarez-Maubecin et al, 2000;Van Bockstaele et al, 2004), other nongap-junctional mechanisms appear to account for initiation and propagation of calcium waves (Charles, 1994(Charles, ,1996Parpura et al, 1994;Hassinger et al, 1995); and 4) ...…”

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Identification of connexin36 in gap junctions between neurons in rodent locus coeruleus

et al. 2007

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Locus coeruleus neurons are strongly coupled during early postnatal development, and it has been proposed that these neurons are linked by extraordinarily abundant gap junctions consisting of connexin32 and connexin26, and that those same connexins abundantly link neurons to astrocytes. Based on the controversial nature of those claims, immunofluorescence imaging and freeze-fracture replica immunogold labeling were used to re-investigate the abundance and connexin composition of neuronal and glial gap junctions in developing and adult rat and mouse locus coeruleus. In early postnatal development, connexin36 and Cx43 immunofluorescent puncta were densely distributed in the locus coeruleus, whereas connexin32 and connexin26 were not detected. By freeze-fracture replica immunogold labeling, connexin36 was found in ultrastructurally-defined neuronal gap junctions, whereas connexin32 and connexin26 were not detected in neurons and only rarely detected in glia. In 28-day postnatal (adult) rat locus coeruleus, immunofluorescence labeling for connexin26 was always co-localized with the glial gap junction marker connexin43; connexin32 was associated with the oligodendrocyte marker CNPase; and connexin36 was never co-localized with connexin26, Cx32 or connexin43. Ultrastructurally, connexin36 was localized to gap junctions between neurons, whereas connexin32 was detected only in oligodendrocyte gap junctions; and Cx26 was found only rarely in astrocyte junctions but abundantly in pia mater. Thus, in developing and adult locus coeruleus, neuronal gap junctions contain connexin36 but do not contain detectable connexin32 or connexin26, suggesting that the locus coeruleus has the same cell-type specificity of connexin expression as observed ultrastructurally in other regions of the central nervous system. Moreover, in both developing and adult locus coeruleus, no evidence was found for gap junctions or connexins linking neurons with astrocytes or oligodendrocytes, indicating that neurons in this nucleus are not linked to the pan-glial syncytium by connexin32-or connexin26-containing gap junctions or by abundant free connexons composed of those connexins. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2008 July 29. Published in final edited form as:Neuroscience. In the developing mammalian central nervous system (CNS), electrical coupling between neurons is well documented by electrophysiological and dye-coupling approaches (Peinado et al., 1993;Fulton, 1995;Montoro and Yuste, 2004;Bruzzone and...

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Section: Light Microscope Immunohistochemistrymentioning

confidence: 54%

Section: Identification Of Neurons Vs Glia In Freeze-fracture Replicasmentioning

confidence: 99%

mentioning

confidence: 99%

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Identification of connexin36 in gap junctions between neurons in rodent locus coeruleus

et al. 2007

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“…33 Although still debated, 34 the presence of Cx26 was also reported in sub-population of astrocytes. 35 Oligodendrocytes are endowed with gap junctions found in almost all areas of their plasma membranes, however, they were not detected between successive layers of myelin. 36 As shown in culture and in brain slices, the coupling efficiency between oligodendrocytes is low compared to astrocytes.…”

Section: Intercellular Communication In Glia and Neuroprotectionmentioning

confidence: 99%

Glia: the fulcrum of brain diseases

et al. 2007

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Neuroglia represented by astrocytes, oligodendrocytes and microglial cells provide for numerous vital functions. Glial cells shape the micro-architecture of the brain matter; they are involved in information transfer by virtue of numerous plasmalemmal receptors and channels; they receive synaptic inputs; they are able to release 'glio'transmitters and produce long-range information exchange; finally they act as pluripotent neural precursors and some of them can even act as stem cells, which provide for adult neurogenesis. Recent advances in gliology emphasised the role of glia in the progression and handling of the insults to the nervous system. The brain pathology, is, to a very great extent, a pathology of glia, which, when falling to function properly, determines the degree of neuronal death, the outcome and the scale of neurological deficit. Glial cells are central in providing for brain homeostasis. As a result glia appears as a brain warden, and as such it is intrinsically endowed with two opposite features: it protects the nervous tissue as long as it can, but it also can rapidly assume the guise of a natural killer, trying to eliminate and seal the damaged area, to save the whole at the expense of the part. The sudden emergence of an intellect, and therefore a human being, which materialised only around a million years ago, remains the main mystery for our self-understanding. Similarly, we still do not know by which steps or transitions the human intellect emerged from the animal kingdom and where the fundamental difference between a man and an animal lies. According to the neuronal doctrine, which governs modern neuroscience since the beginning of the twentieth century, 1,2 the neurone is regarded as a basic information processing unit consisting of dendrites and axons with a unidirectional flow of information from the receiving dendrites via the integrating cell body to the terminal branches of the axon. Neuronal networks, connected through synaptic contacts, are generally considered as the substrate of our intellect.The number and size of neural cells increase with the size of the body and of the brain of mammals. This increasing quantity eventually has caused the generation of a new quality, the intellect. Rather amazingly, however, there is a relatively little difference in the morphology and physiology of neurones between humans and beasts; similarly the density of synaptic contacts in the brains of rodents and humans is more or less constant at around 1100-1300 millions/mm 3 . 3 On the contrary, evolution of the nervous system resulted in great changes in the second type of neural cells, the neuroglia. 4 Indeed, phylogenetic advance in brain complexity and capabilities coincided with a remarkable increase in the number of glial cells: in the rodent cortex the glial to neurone ratio is about 0.3 : 1, whereas in humans the same ratio is several times higher being B1.65:1, 5 while the total number of glial cells in the human brain is B10 (or even more) times larger than in lesser mammals. Astrocytes ...

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“…Gap junction channels are formed by the joining of two hemichannels (connexons) between adjacent cells each composed of hexameric protein subunits called connexins (Cx). Several connexins have been reported to be expressed by astrocytes including connexin 43 (Cx43), connexin 26 (Cx26), and connexin 30 (Cx30) (Altevogt and Paul, 2004;Dermietzel et al, 2000;Nagy et al, 2001Nagy et al, , 2003.…”

Section: Introductionmentioning

confidence: 99%

Modulation of connexin expression and gap junction communication in astrocytes by the gram‐positive bacterium S. aureus

Esen

Shuffield

Syed

et al. 2006

Glia

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Gap junctions establish direct intercellular conduits between adjacent cells and are formed by the hexameric organization of protein subunits called connexins (Cx). It is unknown whether the proinflammatory milieu that ensues during CNS infection with S. aureus, one of the main etiologic agents of brain abscess in humans, is capable of eliciting regional changes in astrocyte homocellular gap junction communication (GJC) and, by extension, influencing neuron homeostasis at sites distant from the primary focus of infection. Here we investigated the effects of S. aureus and its cell wall product peptidoglycan (PGN) on Cx43, Cx30, and Cx26 expression, the main Cx isoforms found in astrocytes. Both bacterial stimuli led to a time-dependent decrease in Cx43 and Cx30 expression; however, Cx26 levels were elevated following bacterial exposure. Functional examination of dye coupling, as revealed by single-cell microinjections of Lucifer yellow, demonstrated that both S. aureus and PGN inhibited astrocyte GJC. Inhibition of protein synthesis with cyclohexamide (CHX) revealed that S. aureus directly modulates, in part, Cx43 and Cx30 expression, whereas Cx26 levels appear to be regulated by a factor(s) that requires de novo protein production; however, CHX did not alter the inhibitory effects of S. aureus on astrocyte GJC. The p38 MAPK inhibitor SB202190 was capable of partially restoring the S. aureus-mediated decrease in astrocyte GJC to that of unstimulated cells, suggesting the involvement of p38 MAPK-dependent pathway(s). These findings could have important implications for limiting the long-term detrimental effects of abscess formation in the brain which may include seizures and cognitive deficits.

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Connexin26 in adult rodent central nervous system: Demonstration at astrocytic gap junctions and colocalization with connexin30 and connexin43

Cited by 195 publications

References 64 publications

Identification of connexin36 in gap junctions between neurons in rodent locus coeruleus

Identification of connexin36 in gap junctions between neurons in rodent locus coeruleus

Glia: the fulcrum of brain diseases

Modulation of connexin expression and gap junction communication in astrocytes by the gram‐positive bacterium S. aureus

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