Effects of AdR-siPTEN on learning capability, memory and extracellular signal-regulated kinase expression in hippocampus of rats with vascular dementia
AbstractThis study investigated the effects of a recombinant adenovirus, AdR-siPTEN, on learning capability, memory and extracellular signal-regulated kinase (ERK) expression in the hippocampus of rats with
vascular dementia (VD). VD was introduced via permanent bilateral common carotid artery ligation (2-VO) in rats. AdR-siPTEN recombinant adenovirus and unrelated control adenovirus AdRFP were independently injected into the hippocampus of VD rats. Four weeks later, Morris water maze test was performed to detect the cognition of rats. Hematoxylin and eosin (HE) and Nissl staining were used to observe cellular morphous and neuronal damage in the hippocampus CA1 region. The mRNA and
protein expression of a phosphatase and tensin homolog deleted on chromosome 10 (PTEN), phosphatidylinositol 3-kinase (PI3K), ERK and cAMP response element-binding (CREB) were detected by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry, respectively. PTEN expression was reduced apparently in hippocampus after RNAi intervation in the AdR-siPTEN
group (P<0.05). Compared with the AdRFP group, rats in the AdR-siPTEN group had significantly shorter escape latency to the invisible platform (except on the first day of test) (P<0.05); and more neurons with regular shape and/or Nissl bodies in hippocampus were observed in the AdR-siPTEN group, suggesting attenuated neuronal damage and degeneration. Additionally, the expression of PI3K, ERK and CREB in hippocampus CA1 region of AdR-siPTEN treatment group was markedly higher than that in the AdRFP group (P < 0.05). However, compared with the normal group, the expression of PI3K, ERK and CREB was dramatically decreased in the AdRFP group (P < 0.05). AdR-siPTEN may improve
the cognition of VD rats, attenuate neuronal damage and promote expression of ERK and CREB, leading to the protective effects on neuronal synaptic plasticity in VD rats. These results suggest that PTEN down-regulation may exert potential therapeutic effects on VD.