Involvement of brain-derived neurotrophic factor (BDNF) in MP4-induced autoimmune encephalomyelitis

Area of Science:

• Neuroscience
• Immunology
• Neuroinflammation

Background:

• The role of brain-derived neurotrophic factor (BDNF) in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), remains incompletely understood.
• BDNF is traditionally recognized for its neuroprotective functions.

Purpose of the Study:

• To investigate the impact of BDNF deficiency on the clinical course, central nervous system (CNS) histopathology, and peripheral immune responses in MP4-induced EAE.
• To elucidate BDNF's specific role in the antigen-specific immune response during EAE.

Main Methods:

• MP4-induced EAE was studied in BDNF-deficient (BDNF -/+) and wild-type (BDNF +/+) mice.
• Clinical scores, CNS inflammation, demyelination, and frequencies of T and B cells in CNS infiltrates were assessed.
• Peripheral MP4-specific T cell responses and T cell function upon mitogen stimulation were analyzed.

Main Results:

• BDNF (-/+) mice exhibited significantly less severe EAE compared to BDNF (+/+) mice, with reduced CNS inflammation and demyelination.
• Frequencies of T and B cells in CNS infiltrates were diminished in BDNF (-/+) mice.
• Peripheral MP4-specific T helper 1 (T(H)1)/T(H)17 responses were attenuated in BDNF (-/+) mice, while responses to ovalbumin were similar between groups.
• No global defect in T cell function was observed in BDNF (-/+) mice.

Conclusions:

• BDNF appears to play a role in supporting and maintaining EAE, potentially through influencing the antigen-specific immune response.
• These findings suggest BDNF's involvement in autoimmune neuroinflammation extends beyond its neuroprotective functions.
• Targeting BDNF may offer a novel therapeutic strategy for multiple sclerosis.