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Neurol Neurochir Pol. 2018 Aug;52(4):483-489. doi: 10.1016/j.pjnns.2018.03.006. Epub 2018 Mar 29.

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

Author information

1
Division of Neurochemistry and Neuropathology, Department of Neurology, Poznan University of Medical Sciences (PUMS), 49 Przybyszewskiego Street, 60-355 Poznan, Poland. Electronic address: akalinowskalyszczarz@ump.edu.pl.
2
Department of Neurology and Cerebrovascular Disorders, Poznan University of Medical Sciences, 34 Dojazd Street, 60-631 Poznan, Poland. Electronic address: mpawlak@ump.edu.pl.
3
Division of Neurochemistry and Neuropathology, Department of Neurology, Poznan University of Medical Sciences (PUMS), 49 Przybyszewskiego Street, 60-355 Poznan, Poland. Electronic address: aleksandra.wyciszkiewicz@gmail.com.
4
Division of Neurochemistry and Neuropathology, Department of Neurology, Poznan University of Medical Sciences (PUMS), 49 Przybyszewskiego Street, 60-355 Poznan, Poland. Electronic address: osztynowiczkr@ump.edu.pl.
5
Department of Neurology, Poznan University of Medical Sciences, 49 Przybyszewskiego Street, 60-355 Poznan, Poland. Electronic address: wkozubski@ump.edu.pl.
6
Division of Neurochemistry and Neuropathology, Department of Neurology, Poznan University of Medical Sciences (PUMS), 49 Przybyszewskiego Street, 60-355 Poznan, Poland. Electronic address: slamic@yahoo.com.

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.

KEYWORDS:

Brain-derived neurotrophic factor (BDNF); Immunomodulation; Neurotrophic factors; Neurotrophins; Relapsing-remitting multiple sclerosis (RRMS)

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