Increased expression of connexin 43 in a mouse model of spinal motoneuronal loss

Abstract

Amyotrophic lateral sclerosis (ALS) is one of the most common motoneuronal disease, characterized by motoneuronal loss and progressive paralysis. Despite research efforts, ALS remains a fatal disease, with a survival of 2-5 years after disease onset. Numerous gene mutations have been correlated with both sporadic (sALS) and familiar forms of the disease, but the pathophysiological mechanisms of ALS onset and progression are still largely uncertain. However, a common profile is emerging in ALS pathological features, including misfolded protein accumulation and a cross-talk between neuroinflammatory and degenerative processes. In particular, astrocytes and microglial cells have been proposed as detrimental influencers of perineuronal microenvironment, and this role may be exerted via gap junctions (GJs)- and hemichannels (HCs)-mediated communications. Herein we investigated the role of the main astroglial GJs-forming connexin, Cx43, in human ALS and the effects of focal spinal cord motoneuronal depletion onto the resident glial cells and Cx43 levels. Our data support the hypothesis that motoneuronal depletion may affect glial activity, which in turn results in reactive Cx43 expression, further promoting neuronal suffering and degeneration.

Clobetasol promotes neuromuscular plasticity in mice after motoneuronal loss via sonic hedgehog signaling, immunomodulation and metabolic rebalancing

“…The sample size for each experiment is reported in figure legends. No statistical methods were used to predetermine sample sizes, but our sample sizes were similar to those reported in previous publications [ 15 , 18 , 48 , 56 ]. Mice were randomly assigned to experimental groups.…”

“…Behavioral impairment was evaluated by two separate observers blind to the treatment analyzing the hind limb posture and gait capability, and assigning a clinical score in accordance with the following criteria described by Albano et al [ 47 , 48 ]. Animals were sacrificed at 42 dpl by intracardial perfusion and organs, i.e.…”

Astrocytes in Amyotrophic Lateral Sclerosis

“…Communication among astrocytes is promoted by connexin-based gap junctions, such as Cx43. Abnormally high Cx43 expression in the cortical and SC astrocytes of mSOD1 mice and ALS patients is associated to astrocyte-mediated neurotoxicity (32).…”

The Multimodal MOPr/DOPr Agonist LP2 Reduces Allodynia in Chronic Constriction Injured Rats by Rescue of TGF-β1 Signalling

“…Nuclei were counterstained with DAPI (1:10.000, Invitrogen, Waltham, MA, United States) for 5 min at RT and then mounted with BrightMount mounting medium (Abcam). Digital images were acquired using a Leica DM IRB fluorescence microscope and with Leica TCS SP8 confocal microscope and profile plots for immunofluorescence images were obtained as previously described (Vicario et al, 2019a;Spitale et al, 2020). Briefly, confocal images of ipsilateral dorsal horns were analyzed using ImageJ software.…”