Phagocyte-mediated synapse removal in cortical neuroinflammation is promoted by local calcium accumulation.Jafari M, Schumacher AM, Snaidero N, Ullrich Gavilanes EM, Neziraj T, Kocsis-Jutka V, Engels D, Jürgens T, Wagner I, Weidinger JDF, Schmidt SS, Beltrán E, Hagan N, Woodworth L, Ofengeim D, Gans J, Wolf F, Kreutzfeldt M, Portugues R, Merkler D, Misgeld T, Kerschensteiner M.Nat Neurosci. 2021 Jan 25. doi: 10.1038/s41593-020-00780-7. Online ahead of print.
Cortical pathology contributes to chronic cognitive impairment of patients suffering from the neuroinflammatory disease multiple sclerosis (MS). How such gray matter inflammation affects neuronal structure and function is not well understood. In the present study, we use functional and structural in vivo imaging in a mouse model of cortical MS to demonstrate that bouts of cortical inflammation disrupt cortical circuit activity coincident with a widespread, but transient, loss of dendritic spines. Spines destined for removal show local calcium accumulations and are subsequently removed by invading macrophages or activated microglia. Targeting phagocyte activation with a new antagonist of the colony-stimulating factor 1 receptor prevents cortical synapse loss. Overall, our study identifies synapse loss as a key pathological feature of inflammatory gray matter lesions that is amenable to immunomodulatory therapy.
So I guess we say NSS if you block microglia you block the disease processes and therefore synapses are saved, we know this is a problem in MS
Synaptic Loss in Multiple Sclerosis Spinal Cord.Petrova N, Nutma E, Carassiti D, Rs Newman J, Amor S, Altmann DR, Baker D, Schmierer K.Ann Neurol. 2020 Sep;88(3):619-625.
Increased expression of colony-stimulating factor-1 in mouse spinal cord with experimental autoimmune encephalomyelitis correlates with microglial activation and neuronal loss.Gushchina S, Pryce G, Yip PK, Wu D, Pallier P, Giovannoni G, Baker D, Bo X.Glia. 2018 Oct;66(10):2108-2125
Hopefully BTKi can resolve this issue and maybe allow the reversal of damage to the synapses, maybe?
All without inhibiting macrophages and microglia to much from carrying out there normal duties but limit damage they may cause. This is surely a fine balance
I maybe a million miles off here, but could some sort of insuin resistance be involved in the process via not enough energy getting into the cell causing cell death. Just a thought.