Inhibition of Oxidative Stress during Developmental Cell Death: Cellular and Behavioral Effects

Dopamine neurons in the substantia nigra during development undergo cell death, which has been described as apoptotic (1,2), with the main apoptotic peak occurring during the perinatal period (1). Several studies have investigated the cellular mechanisms underlying the apoptosis of these neurons, but the precise mechanisms are still poorly understood. In cultured catecholamine cells, tetrahydrobiopterin (BH4) has been shown to participate in the apoptotic cell death process (3). Both dopamine and BH4 metabolism can produce reactive oxygen species, which can cause cellular damage including lipid peroxidation, which is characterized by the formation of lipid byproducts derived from the breakdown of polyunsaturated fatty acids and related esters (6). Reactive oxygen species are actively scavenged by antioxidant enzymes, such as superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx). (−)-Deprenyl is an irreversible inhibitor of monoamine oxidase-B, which has been shown to prevent apoptosis of cultured fetal dopamine neurons through its antioxidant properties (7,8). α-Tocopherol (vitamin E) is a lipophilic antioxidant that can prevent lipid peroxidation, and has been used to reduce neuronal damage induced by neurotoxic agents (9). We have previously shown that deprenyl and α-tocopherol had no protective effects against developmental apoptosis of dopamine neurons (4,5). In present report, we investigated the effects of deprenyl and α-tocopherol on levels of antioxidant enzymes, lipid oxidation, and the locomotor and learning behaviors of rats.