Immune-cell BDNF expression in treatment-naïve relapsing-remitting multiple sclerosis patients and following one year of immunomodulation therapy

Abstract

Although neurons are the main source of neurotrophins in the healthy brain, neurotrophins can also be expressed in the immune system. We have previously shown that in relapsing-remitting multiple sclerosis (RRMS) lower immune-cell neurotrophin levels are associated with brain atrophy and cognitive impairment. The aim of the present study was to assess if immune-cell neurotrophin expression is impaired in MS as compared with the healthy controls, and to describe if these levels change in treatment-naïve RRMS patients, following one year of immunomodulation. Fifty treatment-naïve RRMS patients were assessed at baseline and after one year of immunomodulation (beta-interferons/glatiramer acetate). The control group included 39 healthy subjects matched according to age and gender. Peripheral blood mononuclear cells (PBMCs) were isolated from heparinized blood using Ficoll-Histopaque gradient. The levels of brain-derived-neurotrophic-factor (BDNF), beta-nerve-growth-factor (beta-NGF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5) were measured in PBMC lysates with ELISA. BDNF levels were significantly lower in MS than in the healthy controls (median 613 vs. 1657pg/mg protein, p<0.001). After one year of immunomodulation, BDNF expression did not change significantly (p=0.06) on the group level. In 70% of patients there was no increase in BDNF level, and in 30% it increased. We observed no differences between treatment groups. Other neurotrophins were detected in a minority of MS samples (as opposed to the controls). To conclude, we have shown that immune-cell production of neurotrophins is impaired in MS patients. In our MS cohort standard immunomodulation failed to restore normal BDNF levels in PBMCs within one year of therapy.

Expression Analysis of BDNF Gene and BDNF-AS Long Noncoding RNA in Whole Blood Samples of Multiple Sclerosis Patients: Not Always a Negative Correlation between Them

“…Again, for BDNF-AS none of patients' subgroups showed significance even subgroup of females ˂30 years old (3-fold change). This is well in line with Lindquist and Kalinowska-Łyszczarz works who found no quantitative change in BDNF protein in freshly isolated peripheral blood mononuclear cells (PBMCs) of MS patients, 27,28 and in contrast to those exhibiting significant changes. 19,22 One of the most straightforward explanations for this might be different sample sizes and heterogeneity of MS that, in part, contributes to these results.…”

Serum level of brain-derived neurotrophic factor in patients with relapsing–remitting multiple sclerosis: a potential biomarker for disease activity

“…In contrast to our results, many studies found that BDNF levels in MS patients were significantly lower than those in the healthy control group [16][17][18]. The low BDNF secretion from immune cells of MS patients may be related to reduced neuroprotection [19].…”

The Bu Shen Yi Sui Formula Promotes Axonal Regeneration via Regulating the Neurotrophic Factor BDNF/TrkB and the Downstream PI3K/Akt Signaling Pathway

“…Furthermore, BDNF has neuroprotective effects through regulating the downstream transcription factor cAMP-response element binding protein (CREB) (De Santi et al, 2009). Clinical observation found low levels of BDNF expression in MS patients (Kalinowska-Łyszczarz et al, 2018). Experimental studies also found decreased expression of BDNF in the brain and spinal cord in mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS (Wang et al, 2014).…”