RESUMEN
OBJECTIVES: Cassava (Manihot esculenta Crantz) contains cyanogenic glycosides (linamarin and lotaustralin) that have been associated with neurological disorders in humans and rats. In basal ganglia, the dopaminergic neurons of substantia nigra pars compacta (SNpc) show high cytotoxic susceptibility; therefore, the chronic consumption of cassava (CCC) could induce neurodegeneration in SNpc. In this study we examine the impact of CCC on the integrity of the nigrostriatal system, including apoptosis and microgliosis. MATERIALS AND METHODS: Male Wistar rats were administered cassava juice daily (3.57 g/kg and 28.56 g/kg, per os) or linamarin (0.15 mg/ml, IP), and its effects were evaluated in rota-rod and swim tests at days 7, 14, 21, 28, and 35 of administration. In SNpc, oxidative/nitrosative stress was determined by malondialdehyde/4-hydroxyalkenals (MDA-4-HAD) and nitrite contents. Tyrosine hydroxylase immunoreactivity (TH-IR) was evaluated in SNpc, neostriatum (NE), and nucleus accumbens (NA). Apoptosis and microgliosis were determined by active-caspase-3 (C3) and CD11b/c (OX42) expression in the medial region of SNpc. RESULTS: Chronic administration of cassava juice, or linamarin, increased motor impairment. The rats that received 28.56 g/kg cassava showed increased MDA-4-HAD content in SNpc and nitrite levels in NE with respect to controls. Significant loss of TH-IR in SNpc, NE, and NA was not found. The 28.56 g/kg cassava administration produced dopaminergic atrophy and microgliosis, whereas linamarin induced hypertrophy and C3-related apoptosis in SNpc. CONCLUSION: CCC induces cellular stress on dopaminergic neurons, which could contribute to motor impairment in the rat.
RESUMEN
OBJECTIVES: Parkinson's disease (PD) is characterized by motor and cognitive dysfunctions. The progressive degeneration of dopamine-producing neurons that are present in the substantia nigra pars compacta (SNpc) has been the main focus of study and PD therapies since ages. MATERIALS AND METHODS: In this manuscript, a systematic revision of experimental and clinical evidence of PD-associated cell process was conducted. RESULTS: Classically, the damage in the dopaminergic neuronal circuits of SNpc is favored by reactive oxidative/nitrosative stress, leading to cell death. Interestingly, the therapy for PD has only focused on avoiding the symptom progression but not in finding a complete reversion of the disease. Recent evidence suggests that the renin-angiotensin system imbalance and neuroinflammation are the main keys in the progression of experimental PD. CONCLUSION: The progression of neurodegeneration in SNpc is due to the complex interaction of multiple processes. In this review, we analyzed the main contribution of four cellular processes and discussed in the perspective of novel experimental approaches.
