Dynamic expression of Cx47 in mouse brain development and in the cuprizone model of myelin plasticity

Abstract

The study shows the dynamic expression of connexin47 (Cx47) in oligodendrocytes and myelin of mice, either in myelinogenesis occurring in early development or in an experimental model of new-myelinogenesis of adult mice. Cx47 first appeared in the embryonic mouse brain at E10.5 successively the expression increased, principally in regions populated by developing oligodendrocytes. The expression declined postnatally toward adulthood and immunoreactivity was restricted to a few specific areas, such as the corpus callosum, the striatum, the cerebellum, and the spinal cord. Since the expression of Cx47 in developing oligodendrocytes preceded those of Cx32 and Cx29, a role of Cx47 in myelinogenesis was postulated. This hypothesis was tested in a model of re-myelination, which principally involved the corpus callosum, occurring in adult mice by treatment with cuprizone. Cx47 was upregulated during demyelination and recovered during the remyelination phase. During demyelination, Cx47 was first over-expressed in the corpus callosum and later, when the myelin virtually disappeared in the injured areas, Cx47 was expressed in astrocytes located inside and closely around the demyelinated areas. The remyelination of injured areas occurred after stopping the administration of cuprizone and continued to complete recovery. In this period the expression of Cx47 shifted from astrocytes to newly-formed myelin. Thus, Cx47 exhibits in this model a transient and de novo expression in astrocytes with a topographic segregation in the injured areas, only when oligodendrocytes and the myelin were most severely affected. Taken as a whole the evidence suggests that Cx47 play a key role in myelination.

Oligodendroglia: metabolic supporters of neurons

“…This finding is not surprising given that oligodendrocytes are damaged in MS plaques, whereas astrocytes become more reactive. In the EAE mouse model, connexin expression is quite dynamic: Cx43, Cx47, and Cx32 were severely reduced within demyelinated lesions, but increased in remyelinating regions (98); similar observations were made in the cuprizone mouse model (100). As discussed earlier, loss of astrocyte Cx43/Cx30 suppresses oligodendrocyte maturation, and loss of astrocyte Cx43 inhibits OPC proliferation (76,85).…”

Connexin-based channels contribute to metabolic pathways in the oligodendroglial lineage

“…During brain development, oligodendroglial-specific Cx47 and Cx32 are detected at embryonic stages, whereas Cx29 appears at P0. Cx47 expression increases successively in regions populated with developing oligodendroglia and declines from early postnatal stage to adulthood (Parenti et al, 2010). Here, we used OPC cultures to further demonstrate the dynamic expression pattern of connexins during oligodendroglial development in vitro, suggesting a role for connexin-based channels in this process (Li et al, 2014).…”

“…For instance, connexin 43 (Cx43, also known as GJA1) and connexin 30 (Cx30, also known as GJB6) are mainly expressed in astrocytes (Ransom and Giaume, 2013), whereas Cx47, Cx32 and Cx29 (also known as GJC2, GJB1 and GJC3, respectively) are present in oligodendroglial cells (Parenti et al, 2010;Theis et al, 2005). Recently, pathological changes of oligodendroglia or demyelination found in transgenic mice with different subsets of connexins (i.e.…”

Oxidative stress markers at birth: Analyses of a neonatal population

“…Hsp60 determination by ELISA was performed in a subset of 19 randomized serum samples as described (Rizzo et al, 2012;Parenti et al, 2010), and a commercial kit (Hsp60 human EIA kit, Enzo Life Science, Cat No. ADI-EKS-600, Enzo Life Science AG, Lausen, Switzerland).…”