The Developing Cerebellum as a Target for Toxic Substances: Protective Role of Antioxidants.

Cerebellar development begins during the late embryological period and continues to undergo organizational changes long after birth. The cerebellum is particularly susceptible to developmental abnormalities on exposure to oxidants and free radicals, thus leading to oxidative stress. Oxidative stress occurs when there is an imbalance between reactive oxygen species generation and antioxidant defences which may disrupt signalling pathways, leading to cerebellar anomalies and dysfunction. In this regard, this review assesses current research underlining the importance of the cerebellum, provides an update on substances affecting cerebellar development and highlights some promising antioxidants that may play a role in attenuating toxicity in the developing cerebellum. To accomplish this, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) system was employed and key scientific databases such as Science Direct, PubMed, Scopus, Web of Science and Google Scholar were searched to explore and collect information on the cerebellum and the role of antioxidants during its development. Originally, 109 articles were obtained but 22 articles which met the inclusion criteria were selected for the review. These findings provide an updated compilation of antioxidants capable of attenuating oxidative damage in the developing cerebellum, thus allowing future interdisciplinary studies in the form of clinical applications for screening and possible development of novel therapeutic agents from the identified products.

Attenuation of Endoplasmic Reticulum Stress, Impaired Calcium Homeostasis, and Altered Bioenergetic Functions in MPP+-Exposed SH-SY5Y Cells Pretreated with Rutin.

Parkinson's disease (PD) is a common neurodegenerative disorder that affects approximately 1% of the population over the age of 65 years. While treatment options for PD are limited, reports show that plant-derived bioactive compounds such as rutin possess numerous pharmacological benefits, including antioxidant and antiapoptotic activities. This study aimed to investigate the potential role of rutin in MPP+-treated SH-SY5Y neuroblastoma cells, an established cell model of PD. Our findings reveal increased concentrations of Ca2+ and endoplasmic reticulum (ER) stress as well as impaired mitochondrial membrane potential and bioenergetic status in SH-SY5Y cells treated with MPP+ only. This is demonstrated by a significant reduction in the expression levels of BiP, significantly reduced basal respiration, maximal respiration, and spare respiratory capacity as well as a significant increase in the expression levels of CHOP; however, these effects were significantly attenuated following pretreatment with rutin. Also, rutin significantly improved basal and compensatory glycolysis as a response to an impaired oxidative phosphorylation system triggered by MPP+, characterized by deficient ATP production. In conclusion, our findings provide the first evidence on the ability of rutin to maintain Ca2+ homeostasis, inhibit ER stress, and protect the mitochondria in MPP+-treated SH-SY5Y cells.