Docosahexaenoic acid provides protective mechanism in bilaterally MPTP-lesioned rat model of Parkinson's disease.

Docosahexaenoic acid (DHA), a major polyunsaturated fatty acid (PUFA) in the phospholipid fraction of the brain, is essential for normal cellular function. Neurodegenerative disorders such as Parkinson's disease (PD) often exhibit significant declines in PUFAs. The aim of this study was to observe the effects of DHA supplementation in an experimental rat model of PD created with '1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine' (MPTP). Adult male Wistar rats were divided into four groups: (1) Control; (2) DHA-treated; (3) MPTP-induced; and (4) MPTP-induced + DHA-treated. Motor activity was investigated using the 'vertical pole' and 'vertical wire' tests. The dopaminergic lesion was determined by immunohistochemical analysis for tyrosine hydroxylase (TH)-immunopositive cells in substantia nigra (SN). Immunoreactivities of Bcl-2, Akt and phosphorylated-Akt (p-Akt) in SN were evaluated by immunohistochemistry. MPTP-induced animals exhibited decreased locomotor activity, motor coordination and loss of equilibrium. Diminished Parkinsonism symptoms and decreased dopaminergic neuron death were detected in the MPTP-induced + DHA-treated group compared to the MPTP-induced group. Moderate decreases in Akt staining were found in the MPTP-induced and MPTP-induced + DHA-treated groups compared to controls. p-Akt immunoreactivity decreased dramatically in the MPTP-induced group compared to the control; however, it was increased in the MPTP-induced + DHA-treated group compared to the MPTP-induced group. The staining intensity for Bcl-2 decreased prominently in the MPTP-induced group compared to the control, while it was stronger in the MPTP-induced + DHA-treated group compared to the MPTP-induced group. In conclusion, DHA significantly protects dopaminergic neurons against cell death in an experimental PD model. Akt/p-Akt and Bcl-2 pathways are related to this protective effect of DHA in experimental PD.

Beneficial effects of docosahexaenoic acid on active avoidance performance in 1K-1C hypertensive rats.

The present study evaluated the role of chronic docosahexaenoic acid (DHA) supplementation on active avoidance learning task performance in experimental hypertension. Male Wistar rats were randomly divided into five experimental groups as follows: control, sham, DHA treated, 1K-1C hypertensive, and 1K-1C hypertensive+DHA treated. Hypertension was induced in 1K-1C rats via placing a silver clip (0.20-mm ID) around the left renal artery following a right uninephrectomy. DHA (36 mg/kg/day) was given to the treatment groups for 60 days by gastric gavage. Arterial blood pressure was measured by using the tail-cuff method. Active avoidance responses were determined by an automated shuttle-box. In brain (cerebrum) and hippocampus tissues, thiobarbituric acid reactive substances (TBARS) and nitrite levels were measured by fluorometric methods. DHA supplementation decreased blood pressure in hypertensive rats. Data from active avoidance training indicated that performance of active avoidance learning tasks were significantly impaired in 1K-1C hypertensive rats, but was completely restored by DHA supplementation. Increased cerebrum TBARS levels in 1K-1C rats were abolished by DHA administration. Cerebrum nitrite levels were lower in the DHA, 1K-1C and 1K-1C+DHA treated groups compared to controls. Hippocampus nitrite levels were lower in DHA treated and 1K-1C hypertensive rats compared to controls and higher in 1K-1C+DHA treated rats compared to the 1K-1C group. Our data indicates that DHA supplementation improves the performance of active avoidance learning tasks which is impaired in experimental hypertension. These affirmative changes might be due to a DHA-induced decrease in lipid peroxidation which may in turn limit the consumption of nitric oxide (NO) which promotes active avoidance learning.

The role of docosahexaenoic acid on visual evoked potentials in one kidney-one clip hypertension.

PURPOSE: To investigate the effects of polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) on visual evoked potentials (VEPs) in a one kidney-one clip (1K-1C) hypertension model in rats. METHODS: Five experimental groups were formed: a control group, a sham group, a group supplemented with DHA, a 1K-1C group, and a 1K-1C + DHA group. The DHA groups were treated for 60 days. In the 1K-1C groups, the right kidney was removed and a silver clip with a 0.2-mm gap was placed on the left renal artery. RESULTS: The DHA-supplemented rats had lower blood pressure than their respective controls (p < 0.01). The increased brain and retina thiobarbituric acid reactive substances (TBARS) levels in hypertensive rats were abolished by DHA administration. The brain nitrite levels were lower in the DHA, 1K-1C and 1K-1C + DHA groups compared with the control group (p < 0.01), and the retina nitrite level was higher in the 1K-1C + DHA group compared with the DHA and 1K-1C groups (p < 0.01). There was an improvement of P(2), N(2) and P(3) components following DHA supplementation in 1K-1C hypertensive rats compared with the 1K-1C group. CONCLUSION: The present study suggests that DHA supplementation has the potential to prevent VEP changes caused by an experimental model of hypertension. This state might be related to the lipid peroxidation lowering effect of DHA.