Until recently, members of the connexin gene family were believed to comprise the sole molecular component forming gap junction channels in vertebrates. The recent discovery of the pannexin gene family has challenged this view, as these genes may encode for a putative second class of gap junction proteins in vertebrates. The expression of pannexin genes overlaps with those cellular networks known to exhibit a high degree of gap junctional coupling. We investigated the spatio-temporal mRNA distribution of one member of this gene family, pannexin1 (Panx1), in the brain and retina of mice using quantitative real-time polymerase chain reaction and a combination of in situ hybridization and immunohistochemistry for cellular resolution. Our results demonstrate a widespread expression of Panx1 in the brain, retina and other non-neuronal tissues. In the cortex, cerebellum and eye, Panx1 is expressed at early embryonic time points and peaks around embryonic day 18 followed by a decline towards adulthood. Most notably, Panx1 is detectable in neurons of many brain nuclei, which are known to be coupled by gap junctions as well as in previously unrecognized areas. Abundant expression was found in the adult hippocampal and neocortical pyramidal cells and interneurons, neurons of the reticular thalamus, the inferior olive, magnocellular hypothalamic neurons, midbrain and brain stem motoneurons, Purkinje cells and the retina.

Recent studies indicate that the visual system appears more frequently affected in polyglutamine diseases than expected previously. Here, we investigated retinal degenerations in adult transgenic R6/2 mice, a model for Huntington's disease (HD). Light microscopical analysis revealed retinal dystrophy all over the retina, with central areas showing major effects. Electron microscopical analysis showed strong degenerations of outer and inner photoreceptor segments, shrinkage of photoreceptor cell somata, and signs of degeneration in photoreceptor terminals in the outer plexiform layer. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling showed hints of apoptosis. Mutant huntingtin and ubiquitin were expressed in all classes of retinal neurons, the pigment epithelium, and to a minor extent in neuropil structures. For investigating possible links to functional impairments in the rod-cone pathway, expression levels of three connexins (Cx) were compared in R6/2 and wildtype mice retinae. In R6/2 mice, expression of Cx36, the major neuronal connexin in the retina, was slightly reduced in the outer plexiform layer, indicating affected photoreceptor terminals as detected at the electron microscopical level. In contrast, Cx45, a putative neuronal connexin in the retina, was remarkably reduced in the inner plexiform layer of R6/2 mice. This result corresponded to fainter signals of Cx45 mRNA as documented by in situ hybridization and to a lower level of mCx45 cDNA as obtained by polymerase chain reaction after reverse transcription, suggesting functional deficits in spatial processing of Cx45-mediated gap junction coupling due to transgene-induced retinal degenerations. Thus, it is important to clarify the meaning of visual involvement in HD.

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The contribution of alpha-synuclein accumulation in Alzheimer's disease (AD) plaques is currently a matter of scientific debate. In the present study antisera against the N- and C-terminus, the full-length protein and the central so-called non-amyloid component (NAC) domain of the alpha-synuclein protein were used to address this question in brains of cases with typical AD and of cases with the Lewy body (LB) variant of AD. In typical AD cases, none of the antisera revealed evidence for co-accumulation of alpha-synuclein with extracellular A beta peptides in plaques or in dystrophic neurites decorating the plaque core. Interestingly, cases with mixed pathology of the LB variant of AD revealed accumulation of alpha-synuclein in LBs and in dystrophic neurites of A beta plaques.

Gap junction-mediated electrical coupling contributes to synchronous oscillatory activities of neurons, and considerable progress has been made in defining the molecular composition of gap junction channels. In particular, cloning and functional expression of gap junction proteins (connexins (Cx)) from zebrafish retina have shown that this part of the brain possesses a high degree of connexin diversity that may account for differential functional properties of electrical synapses. Here, we report the cloning and functional characterization of a new connexin, designated zebrafish Cx52.6 (zfCx52.6). This connexin shows little similarity to known connexins from fish and higher vertebrates. By combining in situ hybridization with Laser Capture Microdissection and RT-PCR, we found that this novel fish connexin is expressed in horizontal cells in the inner nuclear layer of the retina. Functional expression of zfCx52.6 in neuroblastoma cells and Xenopus oocytes led to functional gap junctional channels and, in single oocytes, induced large non-junctional membrane currents indicative of the formation of hemichannels, which were inhibited in reversible fashion by raising extracellular Ca 2؉ concentrations.