Abstract
Astrocytes are glial cells organized in dynamic and structured networks in the brain. These plastic networks, involving key proteins such as connexin 43 (Cx43), are engaged in fine neuronal tuning and have recently been considered as emerging therapeutic targets in central nervous system disorders. We developed and validated a new application of the manganese-enhanced magnetic resonance imaging (MEMRI) technique allowing in vivo investigations of astrocyte-neuron interactions through quantification of brain Cx43 functional activity. The proof of concept has been achieved by quantification of MEMRI signals in brain after either local astrocyte-specific Cx43 knockdown with shRNA or systemic administration of Cx43 blockers. Unilateral hippocampal Cx43 genetical silencing was associated with an ipsilateral local increase of MEMRI signal. Furthermore, Cx43 blockers also enhanced MEMRI signal responses in hippocampus. Altogether, these data reveal the MEMRI technique as a tool for quantitative imaging of in vivo Cx43-dependent function in astrocytes under physiological and pathological conditions.
Highlights
Data accumulated over the last decades mainly point out a role for glial cells in providing neurons with metabolic, structural and trophic support[1]
Selective silencing of astrocyte connexin 43 (Cx43) expression in the mouse hippocampus
Data from this study present a new application of manganese-enhanced magnetic resonance imaging (MEMRI) to investigate the functional activity of cerebral astroglial Cx43 in vivo, and to determine the effects of pharmacological blockers of astroglial Cxs in the mouse brain
Summary
Data accumulated over the last decades mainly point out a role for glial cells in providing neurons with metabolic, structural and trophic support[1]. Recent data have shown that astrocytes are key non-neuronal cells involved in active signaling contributing to brain functions, as they notably regulate sleep-wake cycle, cognition[2] and behavior[3]. In vivo brain imaging of the interactions between astrocytes and neurons is still challenging. We developed and validated a new application of the MEMRI technique allowing the direct in vivo investigation of astrocyte-neuron interactions through quantification of hippocampus Cx43 functional activity. To this goal, we used in vivo administration of recombinant lentivirus targeting Cx43 expression and systemic treatments with known connexin modulators in mice
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