Different profiles of apoptosis and activation in children with progressive or static HIV-related encephalopathy

Article type: Research Article

Authors: Blanco, Almudena | Nardacci, Roberta | Del Nonno, Franca | Callea, Francesco | Francalanci, Paola | Piacentini, Mauro^; | Fernández, Ma Ángeles Muñoz^;

Affiliations: Department of Laboratorio Inmuno-Biología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain | National Institute for Infectious Diseases IRCCS "L. Spallanzani", Rome, Italy | Department of Pathology, Children's Hospital Bambino Gesù, Rome, Italy | Department of Biology, University of Rome "Tor Vergata", Rome, Italy | CIBER de Bioquímica, Biomateriales y Nanomedicina, Instituto Salud Carlos III, Zaragoza, Spain

Note: [] Correspondence: Dr. Ma Ángeles Muñoz Fernández, Laboratorio Inmuno-Biología Molecular, Hospital General Universitario Gregorio Marañón, 28007, Madrid, Spain. Tel.: +34 91 5868565; Fax: +34 91 586 8018; E-mail: [email protected]

Abstract: To analyze neurodegeneration in brain cortex samples from human immunodeficiency virus (HIV)-vertically-infected children diagnosed with progressive or static HIV-encephalopathy. We performed a descriptive retrospective and cross-sectional study on 15 HIV-infected children. Eight children were diagnosed with progressive-encephalopathy (EP) and seven with static-EP. Autopsy samples of the frontal cortex from the 15 children were studied. Apoptotic analysis was performed by an assay, which detects apoptotic cells by labeling the fragmentation of DNA by TdT – mediated dUTP nick end labeling (TUNEL) assay. The presence of phosphorylated p53 (p53Ser46P) indicates the beginning of the cell death process. Glial fibrillary acidic protein a marker for glial cells, and p53Ser46P were detected by immunohistochemical assays. All samples from the 15 HIV-infected children showed positive results using TUNEL and showed an increase in p53Ser46P. However, the number of apoptotic cells was higher in samples from children with progressive-EP and was comprised of a higher number of dying neurons than dying glial cells. In contrast, glial cells were more affected in children with static-EP. We observed gliosis (abnormal proliferation of astrocytes in damaged areas of the brain) in all samples, but in the static-EP samples, gliosis was observed in areas close to blood vessels, and it was more pronounced than in progressive-EP samples. Our results suggest that depending whether the diagnosis is progressive-EP or static-EP, neural affliction activates programmed cell death in brain tissue of HIV-infected children. Moreover, there are differences in the type of cellular population affected as well as in the level of glial cell activation.

Keywords: Children, HIV-encephalopathy, central nervous system, apoptosis, p53, glial activation

DOI: 10.3233/JPI-2009-0207

Journal: Journal of Pediatric Infectious Diseases, vol. 4, no. 4, pp. 367-373, 2009