Peripheral and central neuronal ATF3 precedes CD4+ T-cell infiltration in EAE

Area of Science:

• Neuroscience
• Immunology
• Pathology

Background:

• Experimental allergic encephalomyelitis (EAE) is a model for multiple sclerosis (MS), involving T-cell mediated central nervous system (CNS) demyelination.
• EAE exhibits motor dysfunction and neuropathic pain, mirroring MS symptoms.
• Sensory neuron dysfunction may contribute to neuropathic pain in MS and EAE.

Purpose of the Study:

• To investigate the role of sensory neuron injury in EAE.
• To monitor activating transcription factor 3 (ATF3) as a marker of sensory neuron injury.
• To correlate ATF3 expression with T-cell infiltration in the CNS and sensory ganglia during EAE.

Main Methods:

• Induction of EAE in a preclinical model using myelin oligodendrocyte glycoprotein (MOG) and adjuvants.
• Monitoring of ATF3 expression in sensory neurons and T-cell infiltration (CD4+ cells) at various disease stages.
• Administration of adjuvants alone (pertussis toxin, Complete Freund's adjuvant) as controls.

Main Results:

• ATF3 induction in peripheral sensory ganglia and brainstem preceded motor deficits in EAE.
• ATF3 expression was observed before T-cell infiltration, often in adjacent, non-overlapping regions.
• Adjuvants alone induced ATF3 in sensory neurons, while T-cell infiltration required MOG.

Conclusions:

• Clinical manifestations in EAE involve not only central demyelination but also neuronal stress and pathophysiology of sensory neurons.
• ATF3 serves as an early indicator of sensory neuron injury in EAE.
• Sensory neuron dysfunction is a significant factor in EAE pathogenesis, independent of T-cell mediated demyelination.