Aberrant cortical neurogenesis in a pediatric neuroAIDS model: neurotrophic effects of growth hormone.
OBJECTIVE
To study the effects of HIV-1 and feline immunodeficiency virus (FIV) on neural stem cell viability, together with the neurotrophic properties of growth hormone (GH) in models of pediatric neuroAIDS.


METHODS
Mouse neural stem cells were infected in vitro with a Sindbis virus vector (SIN-HIVenv) expressing the envelope protein from the brain-derived HIV-1 strain JR-FL using a vector expressing enhanced green fluorescent protein (SIN-EGFP) as control. Cell survival and alterations in expression of neural stem cell markers upon GH treatment was assessed. Neonatal cats were infected with a neurovirulent FIV strain and 6 weeks after infection treated with GH for 6 weeks. Twelve weeks post-infection, neural progenitor cell marker expression, neuronal loss and neuroinflammation in brain were examined using real time reverse transcription-PCR and immunohistochemical analyses.


RESULTS
HIV-1 envelope expression in neural stem cells reduced nestin expression (P < 0.05) and induced cell death (P < 0.001), which was blocked by GH. In the frontal cortex of FIV-infected cats neuroinflammation, loss of differentiated neurons (P < 0.01) and aberrant neuronal progenitor cell gene expression (P < 0.05) were observed. FIV envelope expression was detected in neural progenitor and monocytoid cells. GH treatment of FIV-infected animals induced insulin-like growth factor-1 expression in neurons (P < 0.01), enhanced neuronal survival (P < 0.01) and increased nestin expression (P < 0.05). Moreover, improved neurobehavioral performance (P < 0.01) and immunological status (P < 0.001) were observed, among GH-treated animals infected with FIV.


CONCLUSIONS
GH protects neural stem cells that are susceptible to lentivirus-mediated injury. Thus, GH may be a potential treatment for pediatric neuroAIDS because of its neurotrophic actions.
van Marle
Guido
G
Department of Microbiology and Infectious Diseases, University of Calgary, Calgary AB, Canada.
Antony
Joseph M
JM
Silva
Claudia
C
Sullivan
Andrea
A
Power
Christopher
C
D015526:AIDS Dementia Complex / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D002415:Cats; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016181:Feline Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000473:pathology; D015752:Genes, env; D013006:Growth Hormone / Q000627:therapeutic use*; D016089:Immunodeficiency Virus, Feline; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D064231:Nestin; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D013234:Stem Cells / Q000187:drug effects / Q000473:pathology*
D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D013006:Growth Hormone