Dose-dependent long-term effects of Tat in the rat hippocampal formation: a design-based stereological study.
The human immunodeficiency virus type 1 (HIV-1) protein transactivator of transcription (Tat) is believed to play a critical role in mediating central nervous system (CNS) pathology in pediatric HIV-1 infection. Long-term neurotoxicity was investigated in a design-based stereology study following intrahippocampal injection of Tat on postnatal day (P)10, a time period that approximates the peak in the rats' rate of brain growth and mimics clinical HIV-1 CNS infection at labor/delivery. The goal was to examine the impact of P10 intrahippocampal Tat injection on the anatomy of the adult hippocampus (5 month) to gain a better understanding about how timing of infection influences the rate of progression of pediatric HIV-1 infection [cf. Fitting et al. (2008a) Hippocampus 18:135-147]. Male P10 Sprague-Dawley rats were bilaterally injected with vehicle or one of three different doses of Tat (5, 25, or 50 mug). Unbiased stereological estimates were used to quantify total neuron number (Nissl stain) in five major subregions of the rat hippocampus: granular layer (GL), hilus of the dentate gyrus (DGH), cornu ammonis fields (CA)2/3, CA1, and subiculum (SUB). Glial cells (astrocytes and oligodendrocytes) were quantified in the DGH and SUB. No significant reduction of neuron number was noted for any of the five hippocampal subregions, in contrast to the very prominent reductions reported when Tat was administered on P1 [Fitting et al. (2008a) Hippocampus 18:135-147]. However, for glial cells, the number of astrocytes in the DGH and SUB as well as the number of oligodendrocytes in the DGH were linear dose dependently increased as a function of dose of Tat. In conjunction with previous stereological research [Fitting et al., (2008a) Hippocampus 18:135-147], the present data suggest that variability in the progression of pediatric HIV/acquired immunodeficiency syndrome (AIDS) may be better understood with the knowledge of the factor of timing of HIV-1 CNS infection.
Fitting
Sylvia
S
Department of Psychology, University of South Carolina, Columbia, South Carolina, USA. sfitting@vcu.edu
Booze
Rosemarie M
RM
Hasselrot
Ulla
U
Mactutus
Charles F
CF
D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000821:virology*; D002452:Cell Count; D004306:Dose-Response Relationship, Immunologic; D006624:Hippocampus / Q000473:pathology / Q000821:virology*; D008297:Male; D009474:Neurons / Q000473:pathology / Q000821:virology*; D009836:Oligodendroglia / Q000473:pathology / Q000821:virology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013995:Time; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage* / Q000235:genetics
D054322:tat Gene Products, Human Immunodeficiency Virus