The Role of Antioxidants in Cerebellar Development: A Review of Literature

Abstract

SUMMARY: Developmental pathologies may result from endogenous or xenobiotic-enhanced formation of reacting oxygen species (ROS), which oxidatively damage cellular macromolecules and/or alter signal transduction, and that the embryonic processes regulating the balance of ROS formation, oxidative DNA damage and repair, and ROS-mediated signal transduction may be important determinants of teratological risk. ROS can oxidize molecular targets such as DNA, protein, lipid in a process called oxidative stress resulting in cellular dysfunction and in utero death or teratogenicity. This review, consisting of literature search of journals and chapters in books aims at highlighting the importance of the cerebellum in controlling various motor activities in the body, as well as substances affecting cerebellar development with a view of providing an insight to the role antioxidants play in cerebellar development. It is interesting to note that the developing brain (especially the cerebellum, cerebrum and hippocampus) is highly vulnerable to the deleterious effects of ROS. Studies have shown that exposure to oxidants in the first trimester is associated with an increased risk of major congenital anomalies, as most vital organs in the body develop and some become functional within this period in offspring. Antioxidants may prevent oxidative damage in degenerative diseases including ageing, cardiovascular diseases, cancer, Alzheimer's disease, stroke and Parkinson's disease as such play a critical role in wellness and health maintenance. INTRODUCTIONThe consumption of some drugs and chemical substances at various doses could cause malformations in certain developing body organs especially when used during critical periods of development. Such malformations could reflect in the gross and microscopic appearances of affected organs in the mature organisms (Moore & Persaud, 1998). The critical stages of development at which such malformations occur in mammals correspond to the pre-natal and early postnatal lives. In the former circumstance, these substances when consumed by the mother, affect the embryos or foetus only if they cross the blood placental barrier. In the latter circumstance, the substances need to have been administered directly to the neonates or suckled in the breast milk in early post-natal life for them to affect development (Moore & Persaud).The cerebellum is a highly organized structure in which the Purkinje cells (Pc) are the sole output of the cerebellar cortex (Altman, 1969(Altman, , 1972a(Altman, , 1972b(Altman, , 1972c, and it is one of the first structure of the brain to differentiate, however, it achieves its mature configuration many months after birth (Wang & Zoghbi, 2001;Bouet et al., 2005). For this reason, the cerebellum is especially vulnerable to developmental irregularities on exposure to oxidants which generate free radicals resulting in oxidative stress (Wang & Zoghbi;Kern & Jones, 2006). Oxidative stress occurs due to an imbalance in pro-oxidant and antioxidant levels. Scientific evidence sugg...

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