2. Academic Validation
  3. Roflumilast: Modulating neuroinflammation and improving motor function and depressive symptoms in multiple sclerosis

Roflumilast: Modulating neuroinflammation and improving motor function and depressive symptoms in multiple sclerosis

  • J Affect Disord. 2024 Jan 12:S0165-0327(23)01543-4. doi: 10.1016/j.jad.2023.12.074.
Zhaowei Wang 1,  Yanxin Zhang 2,  Jiaqing Chai 2,  Yingying Wu 2,  Weiying Zhang 2,  Zhijun Zhang 3
Affiliations

Affiliations

  • 1 Department of Neurology, Affiliated Zhongda Hospital, Research Institution of Neuropsychiatry, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China; Department of Neurology, Shaoxing People's Hospital, 568 Zhonxin Bei Road, Shaoxing City, Zhejiang Province 312000, China.
  • 2 Department of Neurology, Shaoxing People's Hospital, 568 Zhonxin Bei Road, Shaoxing City, Zhejiang Province 312000, China.
  • 3 Department of Neurology, Affiliated Zhongda Hospital, Research Institution of Neuropsychiatry, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China; Shenzhen Key Laboratory of Precision Diagnosis and Treatment of Depression, Department of Mental Health and Public Health, Faculty of Life and Health Sciences, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China. Electronic address: janemengzhang@vip.163.com.
PMID: 38220100 DOI: 10.1016/j.jad.2023.12.074
Abstract

Background: Multiple sclerosis (MS) is an autoimmune disease causing central nervous system demyelination, often associated with depression. Current treatments for MS do not effectively address both physical disability and depression. Roflumilast, a phosphodiesterase-4 inhibitor with anti-inflammatory properties, has shown promise for autoimmune diseases.

Methods: We used an experimental autoimmune encephalomyelitis (EAE) rat model to study roflumilast's effects. Motor dysfunction and depression symptoms were assessed, and histopathological analysis evaluated its anti-inflammatory properties. Flow cytometry examined the drug's impact on brain microglia. TNF-α, IL-1β, and IL-6 levels in hippocampal tissue were assessed using ELISA kits.

Results: Roflumilast improved motor dysfunction and depression symptoms in EAE rats. Histopathological analysis revealed reduced inflammation, demyelination, and axonal loss in the spinal cord. Roflumilast suppressed microglial cell activation and conversion to pro-inflammatory M1-type cells. Flow cytometry showed roflumilast inhibited inflammatory marker expression in microglia and their activation in the hippocampus. IL-6 was identified as a roflumilast target for suppressing hippocampal inflammation.

Limitations: This study used an animal model and did not assess long-term or potential side effects of roflumilast treatment.

Conclusions: Roflumilast holds promise as a treatment for depression and motor impairment in MS. Its anti-inflammatory properties, reducing inflammation and inhibiting microglial activation, suggest its potential for MS therapy. However, further research is needed to evaluate long-term effects and safety in MS patients.

Keywords

Depression; Hippocampus; IL-6; Microglia; Multiple sclerosis; Roflumilast.

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