Effect of endoplasmic reticulum stress involved in manganese‑induced neurotoxicity in rats.

The aim of the present study was to probe the mechanism of apoptosis induced by endoplasmic reticulum stress (ERS) in manganese‑induced rats. A total of 60 Sprague‑Dawley rats were randomly divided into a Vehicle group, LoMag group, HiMag group, and HiMag + 4‑phenylbutyrate (PBA) group. Manganese content was measured by Inductively Coupled Plasma‑Atomic Emission Spectrometry. Pathogenic morphology, the cellular structure of the striatum and ER were observed by hematoxylin and eosin staining and electron microscopy. The TUNEL method was used to examine neuronal apoptosis in the rat striatum. The expression levels of glucose‑regulated protein 78KD (GRP78), C/EBP homologous protein (CHOP), c‑Jun N‑terminal kinase (JNK) and caspase‑12 were analyzed by western blot analysis. The results revealed that striatal manganese concentrations in the LoMag and HiMag groups were higher than that in the Vehicle group (P<0.01). Rat striatal neuronal structure and apoptotic rates in the LoMag and HiMag groups were higher than those in the Vehicle group (P<0.05). 4‑PBA treatment effectively reduced the apoptotic cell number (P<0.05). In addition, ER swelling and vacuolization in the HiMag + PBA group was reduced compared with that in the HiMag group. In addition, the protein expression levels of GRP78, CHOP, JNK and caspase‑12 in the LoMag and HiMag groups were higher than those in the Vehicle group (P<0.05). However, the expression of these four proteins was reduced by 4‑PBA treatment (P<0.05). In conclusion, 4‑PBA significantly reduced the damage and apoptosis induced by manganese exposure in rats.