Secondary progressive MS cerebrospinal fluid induces axonal degeneration in human primary neurons
Sarah Kovalev1, Gillian Ciaccio1, Annie McDermott1, Jamie Wong1, Saud Sadiq1
1Tisch Multiple Sclerosis Research Center of New York
Objective:
To investigate whether multiple sclerosis (MS) cerebrospinal fluid (CSF) induces axonal degeneration in human primary neurons.
Background:
The majority of MS patients present with relapsing-remitting multiple sclerosis (RRMS) that transitions over time to secondary progressive MS (SPMS) characterized by debilitating progression of disability. Neuropathological evidence points to accumulating neurodegeneration as one underlying cause of disease progression, however the exact pathophysiological mechanisms underlying the transition from RRMS to SPMS remain unknown. Here, we investigated whether MS CSF plays a role in the transition from RRMS to SPMS by triggering axonal degeneration.
Design/Methods:
Human primary neurons were plated on poly-L-lysine-coated chamber slides and cultured in media overnight. The following day, the neurons underwent a full media change. On day 5, the neurons were treated with 50% CSF from patients with: 1) RRMS, 2) SPMS, or 3) primary progressive MS (PPMS). Control neurons were observed with media alone. At 1-day post-treatment, human primary neurons were fixed in 4% paraformaldehyde for Tuj1 immunocytochemistry. Axonal degeneration was assessed by measuring neurite length.
Results:
Our preliminary data show that human primary neurons treated with SPMS CSF display significantly shorter average neurite lengths compared to neurons grown in media, as well as neurons incubated with CSF from either RRMS or PPMS patients.
Conclusions:
SPMS CSF, but not RRMS CSF, induces axonal degeneration of human primary neurons, suggesting that CSF factors may contribute to neurodegeneration underlying the transition from RRMS to SPMS. Future experiments will (1) aim to validate these results using CSF samples from a larger cohort of MS patients and (2) elucidate the factor(s) in SPMS CSF responsible for promoting axonal degeneration.