Neuroprotective effects of docosahexaenoic acid against sub-acute manganese intoxication induced dopaminergic and motor disorders in mice.

Manganese (Mn) is an essential metallic trace element involved in several vital biological functions. Conversely, exposure to excessive levels of Mn induces manganism, causing neurodegeneration and symptoms similar to those seen in Parkinson's disease (PD). Docosahexaenoic acid (DHA) is a long-chain polyunsaturated fatty acid exhibiting neuroprotective properties against neurodegenerative diseases and brain injuries and is known to easily incorporate into membrane phospholipids of brain cells and meditates its corrective actions. In the present study, mice were used for a sub-acute Mn intoxication model to investigate DHA neuroprotective potential against Mn neurotoxicity. We also seek to understand the mechanism by which Mn intoxication induces these motor impairments at 30 mg/kg, by pretreatment with DHA at 200 mg/kg and assessment of changes in spontaneous locomotor behavior by open field test (OF), motor coordination using the rotarod test (RR) and strength by mean of weights test (WT). To highlight these effects on brain neurotransmission, we evaluated the tyrosine hydroxylase immunoreactivity (TH-IR) within substantia nigra compacta (SNC) and striatum (St). Results showed that Mn intoxication significantly altered motor behavior parameters including, decreased of traveled distance by 46%, decreased mean speed by 36%, reduced the ability to sustain the rotarod test to 42%; Moreover, a drop score was obtained using weights test and reflecting affected strength in Mn-intoxicated animals. Pretreatment by DHA prevents mice from Mn toxicity and maintain normal spontaneous activity, motor coordination and strength. Data also showed the ability of Mn to disrupt dopamine neurotransmission by altering tyrosine hydroxylase activity in the nigrostriatal pathway while in pretreated animals, DHA prevented this disruption. Data approved the potential neurotoxic effect of Mn as a risk factor of the Parkinsonism onset, and then demonstrated for the first time the neuroprotective and nutraceutical outcomes of DHA in the sub-acute Mn-intoxication animal model.

Crocus sativus restores dopaminergic and noradrenergic damages induced by lead in Meriones shawi: A possible link with Parkinson's disease.

Lead (Pb) is a metal element released into the atmosphere and a major source of environmental contamination. The accumulation and concentration of this metal in a food web may lead to the intoxication of the body, more precisely, the nervous system (NS). In addition, Pb-exposure can cause structural and functional disruption of the NS. Studies have shown that Pb-exposure could be a risk factor in the development of Parkinson's disease (PD). The latter is related to dopaminergic deficiency that may be triggered by genetic and environmental factors such as Pb intoxication. In this study, we have evaluated, in one hand, the neurotoxic effect of Pb (25 mg / kg B.W i.p) for three consecutive days on dopaminergic system and locomotor performance in Merione shawi. In the other hand, the possible restorative potential of C. sativus (CS) (50 mg / kg BW) by oral gavage. The immunohistochemical approach has revealed that Pb-intoxicated Meriones show a significant increase of Tyrosine Hydroxylase (TH) levels within the Substantia Nigra compacta (SNc), Ventral Tegmental Area (VTA), Locus Coeruleus (LC), Dorsal Striatum (DS) and Medial Forebrain Bundle (MFB), unlike the control meriones, a group intoxicated and treated with Crocus sativus hydroethanolic extract (CSHEE) and treated group by CSHEE. Treatment with CSHEE, has shown a real potential to prevent all Pb-induced damages. In fact, restores the TH levels by 92%, 90%, 88%, 90% and 93% in SNc, VTA, LC, DS and MFB respectively, similarly, locomotor activity dysfunction in Pb-intoxicaed meriones was reinstated by 90%. In this study, we have revealed a new pharmacological potential of Crocus sativus that can be used as a neuroprotective product for neurodegenerative disorders, especially, which implying dopaminergic and noradrenergic injuries, like PD, trigged by heavy metals.