Topic: SOD1(G93A)

Perivascular macrophages (PVMs) are a group of resident myeloid cells in the central nervous system (CNS) expressing the CD206 mannose receptor. They play dual roles: clearing harmful substances in healthy states and contributing to increased blood-brain barrier (BBB) in inflammatory states. To investigate their role in Amyotrophic lateral sclerosis (ALS) pathogenesis, we depleted PVMs at the presymptomatic stage in our ALS animal model and examined the effects on disease progression and neuroinflammation.In SOD1(G93A) mutated rats, PVM depletion was achieved via clodronate-loaded liposome int

Altered neuronal excitability and synaptic inputs to motoneurons are part of the pathophysiology of Amyotrophic Lateral Sclerosis. The cAMP/PKA pathway regulates both of them but therapeutic interventions at this level are limited by the lack of knowledge about suitable pharmacological entry points. Here we used transcriptomics on microdissected and in situ motoneurons to reveal the modulation of PKA-coupled receptorome in SOD1(G93A) ALS mice, vs WT, demonstrating the dysregulation of multiple PKA-coupled GPCR, in particular on vulnerable MN, and the relative sparing of β-adrenergic. In vivo M