PubMed Health⌕ Search

Biomedical subjects

B Nadarajah

Publications and source records attributed to B Nadarajah.

5 recordsLinked to original sources

Gap junction-mediated communication in the developing and adult cerebral cortex.

Recent cell biological and electrophysiological studies have shown that gap junctional coupling and the proteins that mediate this form of communication are present in the developing cerebral cortex from early in corticogenesis to the later stage of neuronal circuit formation. We have used electron microscopy to visualize gap junctions in the developing rat cerebral cortex, and studied the expression patterns and cellular localizations of connexin26 (Cx26; beta 2), Cx32 (beta 1) and Cx43 (alpha 1), which take part in their formation. We found that these connexins are expressed differentially during development, and their patterns of expression are correlated with important developmental events such as cell proliferation, migration and formation of cortical neuronal circuits. We also observed that gap junctions and their constituent connexins were abundant in the adult cerebral cortex. Junctions were predominantly between glial cells or between neurons and glia. The frequency and distribution of gap junctions varied in different regions of the adult cortex, possibly reflecting differences in the cellular and functional organization of these cortical areas.

Animals↗

Basic FGF increases communication between cells of the developing neocortex.

We have found that basic fibroblast growth factor (bFGF), applied to cortical progenitor cells in vitro, produces an increase in the expression of the gap junction protein connexin (Cx) 43 and in the mRNA encoding Cx 43. This effect was evident in both proliferating and nonproliferating cells. The elevated levels of mRNA suggest that bFGF is likely to exert its effect by upregulating the rate of transcription of the Cx 43 gene. We have further shown that the increase in Cx 43 expression is mediated through the receptor tyrosine kinase pathway and is associated with enhanced intercellular dye-coupling mediated by gap junctions. These results suggest that gap junction channels provide a direct conduit for mitogens released in response to bFGF to effectively regulate proliferation during corticogenesis.

Animals↗

Differential expression of connexins during neocortical development and neuronal circuit formation.

Gap junctions are membrane channels that mediate the direct passage of ions and molecules between adjacent cells. Recent tracer coupling and optical recording studies have revealed the presence of gap junction-mediated communication between neurons during neocortical development. We have visualized gap junctions in the developing rat cerebral cortex with electron microscopy and studied the pattern of expression and cellular localization of connexins 26, 32, and 43 that take part in their formation. We found that these connexins (Cxs) are expressed differentially during development, and their patterns of expression are correlated with important developmental events such as cell proliferation, migration, and formation of cortical neuronal circuits. Specifically, we observed that the developmental profile of Cx 26 during the first 3 weeks of postnatal life matched closely the development of neuronal coupling, suggesting that coupled neurons use this gap junction protein during circuit formation in the cortex. The subsequent diminution of Cx 26 was mirrored by an increase in Cx 32 immunoreactivity, which became pronounced at the late stages of cortical maturation. In contrast, Cx 43 was localized in the cortex throughout the period of development. Its localization in radial glial fibers closely associated with migrating neurons suggests that this Cx may be involved in neuronal migration.

Animals↗

Gap junctions in the adult cerebral cortex: regional differences in their distribution and cellular expression of connexins.

Gap junctions are membrane channels that mediate electrical and metabolic coupling between adjacent cells. Immunocytochemical analysis by using a panel of anti-connexin antibodies, as well as electron microscopy of thin sections and freeze-fracture replicas, has shown that gap junctions and their constituent proteins are abundant in the cerebral cortex of the adult rat. Their frequency and distribution vary in different cortical regions, which may reflect differences in the cellular and functional organization of these areas of the cortex. Gap junctions were identified between glial cells and, less frequently, between neuronal elements. Heterologous junctions were also identified between astrocytes and oligodendrocytes and between neurons and glia; the latter category included abundant junctions between astrocytic processes and neurons. Double-antibody labelling experiments in tissue sections and in acutely dissociated cells showed that connexin 32 was expressed in neurons and oligodendrocytes, whereas connexin 43, widely believed to be expressed only in astrocytes, was also localized in a population of cortical neurons. These results show that gap junctions can provide a major nonsynaptic means of communication between cortical cell types.

Animals↗

The effect of pralidoxime chloride in the assay of acetylcholinesterase using 5,5'-dithio-bis(2-nitrobenzoic acid) (Ellman's reagent).

Pralidoxime chloride (PAM) hydrolyzes acetylthiocholine, the substrate used in the assay of red cell cholinesterase. The thiocholine that is produced forms a yellow complex when Ellman's reagent is used in the assay. This was tested in blood samples of patients who were treated with PAM after organophosphorus (OP) poisoning and after the observation of an immediate increase in absorption of light at 412 nm.

Acetylcholinesterase↗