Time course study of protein disulfide isomerase activity, body weight and brain volume in the striatum of male rats in neurotoxic model of Huntington disease

Background and Aim : Huntington disease (HD) is a neurodegenerative disorder characterized by unwanted choreatic movements, behavioral disturbances and dementia. Evidences indicate that dysregulation of intracellular neuronal calcium signaling plays important role in HD. Disruption of calcium concentration within the endoplasmic reticulum activates transcriptional cascades and translates proteins involved in the calcium signaling pathway. Among these proteins, Protein Disulfide Isomerase (PDI) is a peptide that is present in the luminal membrane of the endoplasmic reticulum as chaperone, which integrates the endoplasmic reticulum and protects cell survival.Methods : 3-nitropropionic acid (3-NP) injected to induce Huntington neurotoxic model. Adult male rats (250-300 g) were divided into six groups: control group and five groups that they received 3-NP (20 mg/kg ip) in 1,2,3,4 or 5 days (just once per day). At the end of treatment, brains removed and striatum of them were kept for enzyme test to assay PDI activity level. For detection of cell death coronal sections stained with Hematoxylin & Eosin and for measurement of brain volume brains were handled and cut macroscopically with brain matrix and razor into parallel sections. Slice thickness was 2 mm. Eventually Body weight measured every day. Data were analyzed using GraphPad Prism.Results : The result of this study shows that PDI enzyme activity decreased significantly only by receiving 1 dose of 3-NP. The activity of enzyme showed a greater decrease on the second day compared to the first day. The activity of the enzyme decreased with increasing toxin intake (up to day 5). During days of injection by increasing dose of 3-NP, brain volume and body weight decreased. Furthermore, striatum neurons moved gradually toward cell death.Conclusion : The results showed that five days of 3-NP injection led to decline of PDI activity. Also brain volume and body weight decreased and during these days striatum neurons moved gradually toward cell death.

Keywords:

Huntington disease , PDI , Brain volume , Body weight , Cell death