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.

DESIGN AND 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.

CONCLUSION: 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.

Medienart:

Artikel

Erscheinungsjahr:

2005

Erschienen:

2005

Enthalten in:

Zur Gesamtaufnahme - volume:19

Enthalten in:

AIDS (London, England) - 19(2005), 16 vom: 04. Nov., Seite 1781-91

Sprache:

Englisch

Beteiligte Personen:

van Marle, Guido [VerfasserIn]
Antony, Joseph M [VerfasserIn]
Silva, Claudia [VerfasserIn]
Sullivan, Andrea [VerfasserIn]
Power, Christopher [VerfasserIn]

Themen:

9002-72-6
Growth Hormone
Intermediate Filament Proteins
Journal Article
Nerve Tissue Proteins
Nes protein, mouse
Nestin
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 13.06.2006

Date Revised 18.07.2019

published: Print

Citation Status MEDLINE

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM158374428