UCLA

Multiple Sclerosis (MS) is a heterogeneous disease that impacts the brain, spinal cord, and optic nerve. The etiology of MS is not completely understood, but the nature of these autoimmune inflammatory and neurodegenerative lesions has been under investigation for decades. Biological aging has been reported to be more than a significant factor associated with neurodegenerative diseases. Thalamic grey matter atrophy in MS has increasingly been demonstrated with normal aging, and a sexual dimorphism over time has been reported even at the earliest forms of the disease. The thalamus is a critical relay center, and the association of the thalamus in MS has been linked to various clinical symptoms ranging from vision loss, motor deficits, cognitive impairment, numbness, and fatigue. Using the preclinical model of MS, experimental autoimmune encephalomyelitis (EAE), we assessed the neuropathology of thalamic grey matter and spinal cord white matter in sex-matched and age-matched wild-type mice to better understand the motor disability seen in MS and EAE. The experiment with healthy controls and EAE middle age and young mice revealed significant widespread microglia activation, astrocyte activation, and synaptic loss in aged mice. This neuropathology in the MS model during aging suggests that similar neuropathology may contribute to thalamic grey matter atrophy in progressive MS. The role of biological aging witnessed in thalamic network injury in EAE and MS related symptoms is key in highlighting the manifestation of variable lesions that are influenced by biological sex and aging.