Semaphorin4A causes loss of mature oligodendrocytes and demyelination in vivo

Brian Chiou, Elizabeth Neely, Asha Kallianpur, James Connor

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Inappropriate contact between the immune system and the central nervous system is thought to be a cause of demyelination. We previously reported the ability of the class IV semaphorin, Semaphorin4A (Sema4A), to induce apoptosis in human oligodendrocytes; however, these results have yet to be translated to an in vivo setting. Importantly, HIV-associated neurocognitive disorder remains a significant complication for patients on combined anti-retroviral therapy, with white matter damage seen on MRI. Methods: Human cerebrospinal fluid and serum was assayed for Sema4A using a Sema4A-specific ELISA. Wild-type mice were injected with Sema4A via stereotaxic infusion. Data was assessed for significance using unpaired t tests, comparing the corpus callosum of PBS-injected mice versus Sema4A-injected mice. Results: Here, we demonstrate elevated levels of Sema4A in the cerebrospinal fluid and serum of people with HIV infection. Furthermore, we demonstrate that direct injection of Sema4A into the corpus callosum of mice results in loss of myelin architecture and decreased myelin, concomitant with apoptosis of mature myelinating oligodendrocytes. Sema4A injection also causes increased activation of microglia. Conclusions: Taken together, our data further establish Sema4A as a potentially significant mediator of demyelinating diseases and a direct connection between the immune system and oligodendrocytes.

Original languageEnglish (US)
Article number28
JournalJournal of Neuroinflammation
Volume16
Issue number1
DOIs
StatePublished - Feb 8 2019

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Oligodendroglia
Demyelinating Diseases
Corpus Callosum
Myelin Sheath
Cerebrospinal Fluid
Immune System
Apoptosis
Injections
Aptitude
Microglia
Serum
HIV Infections
Central Nervous System
Enzyme-Linked Immunosorbent Assay
HIV
Therapeutics

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Immunology
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Chiou, Brian ; Neely, Elizabeth ; Kallianpur, Asha ; Connor, James. / Semaphorin4A causes loss of mature oligodendrocytes and demyelination in vivo. In: Journal of Neuroinflammation. 2019 ; Vol. 16, No. 1.
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Semaphorin4A causes loss of mature oligodendrocytes and demyelination in vivo. / Chiou, Brian; Neely, Elizabeth; Kallianpur, Asha; Connor, James.

In: Journal of Neuroinflammation, Vol. 16, No. 1, 28, 08.02.2019.

Research output: Contribution to journalArticle

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