Journal of Neuroimmune Pharmacology

, Volume 7, Issue 2, pp 388–400

Suppression of Immunodeficiency Virus-Associated Neural Damage by the p75 Neurotrophin Receptor Ligand, LM11A-31, in an In Vitro Feline Model

  • Rick B. Meeker
  • Winona Poulton
  • Wen-hai Feng
  • Lola Hudson
  • Frank M. Longo
ORIGINAL ARTICLE

Abstract

Feline immunodeficiency virus (FIV) infection like human immunodeficiency virus (HIV), produces systemic and central nervous system disease in its natural host, the domestic cat, that parallels the pathogenesis seen in HIV-infected humans. The ability to culture feline nervous system tissue affords the unique opportunity to directly examine interactions of infectious virus with CNS cells for the development of models and treatments that can then be translated to a natural infectious model. To explore the therapeutic potential of a new p75 neurotrophin receptor ligand, LM11A-31, we evaluated neuronal survival, neuronal damage and calcium homeostasis in cultured feline neurons following inoculation with FIV. FIV resulted in the gradual appearance of dendritic beading, pruning of processes and shrinkage of neuronal perikarya in the neurons. Astrocytes developed a more activated appearance and there was an enhanced accumulation of microglia, particularly at longer times post-inoculation. Addition of 10 nM LM11A-31, to the cultures greatly reduced or eliminated the neuronal pathology as well as the FIV effects on astrocytes and microglia. LM11A-31 also, prevented the development of delayed calcium deregulation in feline neurons exposed to conditioned medium from FIV treated macrophages. The suppression of calcium accumulation prevented the development of foci of calcium accumulation and beading in the dendrites. FIV replication was unaffected by LM11A-31. The strong neuroprotection afforded by LM11A-31 in an infectious in vitro model indicates that LM11A-31 may have excellent potential for the treatment of HIV-associated neurodegeneration.

Keywords

Dementia Encephalitis Inflammation Therapy HIV FIV 

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Rick B. Meeker
    • 1
  • Winona Poulton
    • 1
    • 2
  • Wen-hai Feng
    • 1
    • 3
  • Lola Hudson
    • 4
  • Frank M. Longo
    • 5
  1. 1.Department of NeurologyUniversity of North CarolinaChapel HillUSA
  2. 2.Research Triangle InstituteResearch Triangle ParkUSA
  3. 3.State Key Laboratories for AgrotechnobiologyChina Agricultural UniversityBeijingChina
  4. 4.Department of Molecular Biomedical Sciences, College of Veterinary MedicineNorth Carolina State UniversityRaleighUSA
  5. 5.Department of Neurology and Neurological SciencesStanford University School of MedicineStanfordUSA

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