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Brain-derived neurotrophic factor in patients with multiple sclerosis
Paola Sarchielli1, Laura Greco, Antonio Stipa
1Neuroscience Department, University of Perugia, Policlinico Monteluce, Via E Dal Pozzo 79, 06126 Perugia, Italy. neuro@netemedia.net
Unlabelled:
The aim of the present research was to verify the production of BDNF by peripheral blood mononuclear cells (PBMCs), unstimulated and stimulated with phytohemagglutinin (PHA), anti-OKT3 Ab and myelin basic protein (MBP), in 35 patients affected by multiple sclerosis (MS), 20 with relapsing-remitting (R-R) MS and 15 with secondary progressive (SP) MS. Seven R-R MS patients were assessed during the attack, in the subsequent recovery phase and also 3 months after relapse. The production of BDNF by PBMCs was also evaluated in 20 age- and sex-matched control subjects. Levels of BDNF were also determined in CSF of both patient groups and 20 control subjects.
Results:
Levels of BDNF (pg/ml) in the supernatants of unstimulated and PHA-, anti-OKT3 Ab- and MBP-stimulated PBMCs in patients with R-R MS were significantly higher during relapse and in the recovery phase compared with values detected in the stable phase of the disease. Significantly lower BDNF values were found in unstimulated and stimulated PBMC supernatants of patients with SP MS compared to control subjects. This reduction was greater in patients with a 1-point increase in the EDSS score in the last 6 months compared with that in patients without a progression of the disability score. Reduction in the levels of BDNF was also confirmed in the CSF of SP MS patients compared with R-R MS patients assessed during a stable phase of the disease and control subjects.
Discussion:
On the basis of recent experimental findings, a neuroprotective effect of BDNF produced by inflammatory cells can be hypothesized during relapses in MS. This can favor remyelination. The reduced production of BDNF by PBMCs of patients with SP MS can contribute to the progression of demyelinating disease and axonal loss in this form.
Insights
Brain-derived neurotrophic factor (BDNF) levels are elevated during multiple sclerosis (MS) relapses but reduced in progressive MS, suggesting a role in disease activity and neuroprotection.
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Multiple Sclerosis (MS) is a chronic demyelinating disease of the central nervous system.
- Brain-Derived Neurotrophic Factor (BDNF) plays a crucial role in neuronal survival, growth, and differentiation.
- The role of BDNF in different phases and subtypes of MS requires further elucidation.
Purpose of the Study:
- To investigate BDNF production by peripheral blood mononuclear cells (PBMCs) in patients with relapsing-remitting (R-R) MS and secondary progressive (SP) MS.
- To compare BDNF levels in PBMCs and cerebrospinal fluid (CSF) between MS patients and healthy controls.
- To assess the correlation between BDNF levels and disease activity/progression in MS.
Main Methods:
- BDNF production was measured in unstimulated and stimulated PBMCs (PHA, anti-OKT3 Ab, MBP) from 35 MS patients (20 R-R MS, 15 SP MS) and 20 controls.
- PBMC stimulation assays were performed during different disease phases (relapse, recovery, stable) in R-R MS patients.
- BDNF levels were also quantified in CSF samples from both patient groups and controls.
Main Results:
- PBMC-derived BDNF levels were significantly higher during relapse and recovery phases in R-R MS patients compared to the stable phase.
- SP MS patients exhibited significantly lower BDNF levels in both unstimulated and stimulated PBMCs compared to controls.
- Reduced BDNF levels in SP MS correlated with increased disability scores (EDSS) and were also observed in their CSF compared to R-R MS and controls.
Conclusions:
- Elevated BDNF production by inflammatory cells during MS relapses may indicate a neuroprotective role and potential for remyelination.
- Diminished BDNF production in SP MS patients suggests a contribution to disease progression, including demyelination and axonal loss.
- BDNF levels in PBMCs and CSF serve as potential biomarkers for different MS disease courses.