ObjectiveToexplore the role of HIV-1 tat gene variations in AIDSdementia complex(ADC) pathogenesis.
MethodsHIV-1tat genes derived from peripheral spleen and central basal ganglia of anAIDSpatient with ADC and anAIDSpatientwithoutADC were cloned for sequence analysis. HIV-1 tat genesequence alignmentwasperformed by using CLUSTAL W andthephylogentic analysiswas conductedbyusing Neighbor-joining with MEGA4 software.All tat genes wereused to construct recombinant retroviral expressing vector MSCV-IRES-GFP/tat. The MSCV-IRES-GFP/tat was cotransfected into 293T cells with pCMV-VSV-G and pUMVC vectorsto assemble the recombinant retrovirus. After infection of gliomas U87 cells with equal amount of the recombinant retrovirus, TNF-α, and IL-1β concentrations inthe supernatant of U87 cells were determined with ELISA.
ResultsHIV-1tat genes derived from peripheral spleen and central basal ganglia ofthe AIDS patient with ADC andtheother onewithoutADCexhibited genetic variations.Tat variations and amino acid mutation sites existed mainly at Tat protein core functional area (38-47aa). All Tat proteinscould induce U87 cells to produce TNF-α and IL-1β, but thelevel of IL-1β production was different among Tatproteins derived fromtheADC patient’s spleen, basal ganglia, andthenon-ADC patient’s spleen.The level ofTat proteinsderived fromtheADC patient’s spleen,basal ganglia, andthenon-ADC patient’sspleen were obviously higher thanthat fromthe non-ADC patient’s basal ganglia.
ConclusionTat protein core functional area (38-47aa) mayserve as the key area of enhancing the secretion of IL-1β.This may be related with the neurotoxicity of HIV-1 Tat.
ObjectiveToexplore the role of HIV-1 tat gene variations in AIDSdementia complex(ADC) pathogenesis.
MethodsHIV-1tat genes derived from peripheral spleen and central basal ganglia of anAIDSpatient with ADC and anAIDSpatientwithoutADC were cloned for sequence analysis. HIV-1 tat genesequence alignmentwasperformed by using CLUSTAL W andthephylogentic analysiswas conductedbyusing Neighbor-joining with MEGA4 software.All tat genes wereused to construct recombinant retroviral expressing vector MSCV-IRES-GFP/tat. The MSCV-IRES-GFP/tat was cotransfected into 293T cells with pCMV-VSV-G and pUMVC vectorsto assemble the recombinant retrovirus. After infection of gliomas U87 cells with equal amount of the recombinant retrovirus, TNF-α, and IL-1β concentrations inthe supernatant of U87 cells were determined with ELISA.
ResultsHIV-1tat genes derived from peripheral spleen and central basal ganglia ofthe AIDS patient with ADC andtheother onewithoutADCexhibited genetic variations.Tat variations and amino acid mutation sites existed mainly at Tat protein core functional area (38-47aa). All Tat proteinscould induce U87 cells to produce TNF-α and IL-1β, but thelevel of IL-1β production was different among Tatproteins derived fromtheADC patient’s spleen, basal ganglia, andthenon-ADC patient’s spleen.The level ofTat proteinsderived fromtheADC patient’s spleen,basal ganglia, andthenon-ADC patient’sspleen were obviously higher thanthat fromthe non-ADC patient’s basal ganglia.
ConclusionTat protein core functional area (38-47aa) mayserve as the key area of enhancing the secretion of IL-1β.This may be related with the neurotoxicity of HIV-1 Tat.

In the central nervous system, Asiaticoside has been shown to attenuatein vitro neuronal damage caused by exposure toβ-amyloid.In vivo studies demonstrated that Asiaticoside could attenu-ate neurobehavioral, neurochemical and histological changes in transient focal middle cerebral artery occlusion animals. In addition, Asiaticoside showed anxiolytic effects in acute and chronic stress animals. However, its potential neuroprotective properties in glutamate-induced excito-toxicity have not been fully studied. We investigated the neuroprotective effects of Asiaticoside in primary cultured mouse cortical neurons exposed to glutamate-induced excitotoxicity invoked by N-methyl-D-aspartate. Pretreatment with Asiaticoside decreased neuronal cell loss in a con-centration-dependent manner and restored changes in expression of apoptotic-related proteins Bcl-2 and Bax. Asiaticoside pretreatment also attenuated the upregulation of NR2B expression, a subunit of N-methyl-D-aspartate receptors, but did not affect expression of NR2A subunits. Additionally, in cultured neurons, Asiaticoside significantly inhibited Ca2+ influx induced by N-methyl-D-aspartate. These experimental ifndings provide preliminary evidence that during excitotoxicity induced by N-methyl-D-aspartate exposure in cultured cortical neurons, the neu-roprotective effects of Asiaticoside are mediated through inhibition of calcium inlfux. Aside from its anti-oxidant activity, down-regulation of NR2B-containing N-methyl-D-aspartate receptors may be one of the underlying mechanisms in Asiaticoside neuroprotection.

Impaired iron homeostasis may cause damage to dopaminergic neurons and is critically involved in the pathogenesis of Parkinson’s disease. At present, very little is understood about the effect of neonatal iron intake on behavior in aging animals. Therefore, we hypothesized that increased neonatal iron intake would result in signiifcant behavior abnormalities and striatal dopamine depletion during aging, and Sirtuin 2 contributes to the age-related neurotoxicity. In the present study, we observed that neonatal iron intake (120 μg/g per day) during postnatal days 10–17 resulted in significant behavior abnormalities and striatal dopamine depletion in aging rats. Furthermore, after AK-7 (a selective Sirtuin 2 inhibitor) was injected into the substantia nigra at postnatal 540 days and 570 days (5 μg/side per day), striatal dopamine depletion was signiifcant-ly diminished and behavior abnormality was improved in aging rats with neonatal iron intake. Experimental ifndings suggest that increased neonatal iron intake may result in Parkinson’s dis-ease-like neurochemical and behavioral deifcits with aging, and inhibition of Sirtuin 2 expression may be a neuroprotective measure in Parkinson’s disease.

Changes in neurotransmitter levels in the brain play an important role in epilepsy-like attacks after pregnancy-induced preeclampsia-eclampsia. Metabotropic glutamate receptor 1 participates in the onset of lipid metabolism disorder-induced preeclampsia. Pregnant rats were fed with a high-fat diet for 20 days. Thus, these pregnant rats experienced preeclampsia-like syndromes such as tension and proteinuria. Simultaneously, metabotropic glutamate receptor 1 mRNA and protein ex-pressions were upregulated in the rat hippocampus. These findings indicate that increased sion of metabotropic glutamate receptor 1 promotes the occurrence of high-fat diet-induced preec-lampsia in pregnant rats.