Neuronal nitric oxide synthase phosphorylation induced by docosahexaenoic acid protects dopaminergic neurons in an experimental model of Parkinson’s disease

Introduction. Docosahexaenoic acid (DHA) has been shown to have beneficial effects on Parkinson’s disease(PD). The aim of this study was to investigate if the DHA acts on neurons of substantia nigra (SN) by phosphorylation of neuronal nitric oxide synthase (nNOS) in an experimental mouse model of PD.Material and methods. An experimental model of PD was created by intraperitoneal injections (4 × 20 mg/kg)of the neurotoxin 1-methyl-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). Three-month-old male C57BL/6 micewere randomly divided into four groups as follows: control (C), DHA-treated (DHA), MPTP-injected (MPTP)and DHA-treated and MPTP-injected (DHA + MPTP). DHA (36 mg/kg/day) was administered daily by gavagefor four weeks. Motor activity of the mice was evaluated with pole, locomotor activity and rotarod tests. Caspase-3activity, nitrate/nitrite and 4-hydroxynonenal (4-HNE) levels were determined by spectrophotometric assays.Immunohistochemistry was used to localize and assess the expressions of tyrosine hydroxylase (TH), nNOS andphospho-nNOS (p-nNOS) in SN.Results. An increased return and total down time in the MPTP group was observed in the pole test, while DHAtreatment decreased both parameters. The ambulatory activity, total distance and total locomotor activities weredecreased in the MPTP group, whereas they were increased by DHA treatment. MPTP-treated animals exhibitedshorter time on the rod test which was significantly increased by DHA treatment. DHA administration significantlydecreased 4-HNE and nitrate/nitrite levels of SN supernatants and protected the TH (+) dopaminergicneurons of SN in the DHA + MPTP group compared to the MPTP group. DHA treatment significantly decreasednNOS and increased p-nNOS immunoreactivities in the DHA + MPTP group compared to the MPTP group.Conclusions. These results indicate that DHA treatment protects dopaminergic neurons in SN via increasingnNOS serine 852 phosphorylation in the experimental mice model of PD

Effects of excess vitamin B6 intake on cerebral cortex neurons in rat: an ultrastructural study

The aim of this study was to investigate whether excess of vitamin B6 leads to ultrastructural changes in cerebral cortex of forty-eight healthy albino rats which were included in the study. Saline solution was injected to to the control groups (CG-10, n=12 for 10 days; CG-15, n=12 for 15 days; CG-20, n=12 for 20 days). The three experimental groups (EG-10, n=12; EG-15, n=12; EG-20, n=12) were treated with 5 mg/kg vitamin B6 daily for 10 days (EG-10), 15 days (EG-15) and 20 days (EG-20). Brain tissues were prepared by glutaraldehyde-osmium tetroxide double fixation for ultrastructural analysis. No significant changes were observed in the control groups. The ultrastructural analysis revealed that the numbers of damaged mitochondria, lipofuscin granules and vacuoles were significantly higher in all the experimental groups than in the control groups (

Effects of rosmarinic acid on cognitive and biochemical alterations in ovariectomized rats treated with D-galactose

Introduction. Animal models designed to mimic certain features of Alzheimer’s disease (AD) can help us to in­crease our understanding of the underlying mechanisms of disease. Previous studies have revealed that long-term D-galactose injection combined with ovariectomy results in pathophysiologic alterations associated with AD. Thus, the aim of the present study was to investigate the effects of rosmarinic acid (RA) administration on pathological changes associated with ovariectomy and D-galactose injection, which serve as a two-insult model for AD. Material and methods. One hundred female Wistar rats were divided into five equal groups: control (C), Sham (Sh), rosmarinic acid treated (R), ovariectomized rats treated with D-galactose (OD), ovariectomized rats treated with D-galactose and rosmarinic acid (ODR) groups. D-galactose (80 mg/kg/day) was administered by i.p. injection and RA (50 mg/kg/day) was given via gavage for 60 days. Open field and Y-maze tests were used to assess locomotor activity and short-term spatial memory, respectively. Biochemical and histopathological analyses of the brain tissue were performed. Results. Open field testing showed that the locomotor activity and exploratory behavior of rats were prominent­ly impaired in the OD group as compared to the other studied groups. Similarly, Y-maze test results revealed a decrease of short-term spatial memory in the OD rats. A concomitant treatment with RA significantly restored altered locomotor activity and cognitive functions in the ODR group. Lipid peroxidation levels, cyclooxygen­ase-2 expression and prostaglandin E2 levels in the brain tissue were higher in the OD group and RA treatment inhibited these changes. AD-like histopathological alterations and amyloid b peptide (Ab) depositions were observed in the OD group. Normal cell structure and lower Ab depositions were observed in the ODR group compared with the OD group. Conclusions. RA could have the potential to prevent some psychological and biochemical alterations of brain tissue found in a rat model of AD probably by attenuating lipid peroxidation and inflammatory response

The effects of docosahexaenoic acid on glial derived neurotrophic factor and neurturin in bilateral rat model of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder marked by cell death in the Substantia nigra (SN). Docosahexaenoic acid (DHA) is the major polyunsaturated fatty acid (PUFA) in the phospholipid fraction of the brain and is required for normal cellular function. Glial cell line derived neurotrophic factor (GDNF) and neurturin (NTN) are very potent trophic factors for PD. The aim of the study was to evaluate the neuroprotective effects of GDNF and NTN by investigating their immunostaining levels after administration of DHA in a model of PD. For this reason we hypothesized that DHA administration of PD might alter GDNF, NTN expression in SN. MPTP neurotoxin that induces dopaminergic neurodegeneration was used to create the experimental Parkinsonism model. Rats were divided into; control, DHA-treated (DHA), MPTP-induced (MPTP), MPTP-induced+DHA-treated (MPTP+DHA) groups. Dopaminergic neuron numbers were clearly decreased in MPTP, but showed an increase in MPTP+DHA group. As a result of this, DHA administration protected dopaminergic neurons as shown by tyrosine hydroxylase immunohistochemistry. In the MPTP+DHA group, GDNF, NTN immunoreactions in dopaminergic neurons were higher than that of the MPTP group. In conclusion, the characterization of GDNF and NTN will certainly help elucidate the mechanism of DHA action, and lead to better strategies for the use of DHA to treat neurodegenerative diseases

effect of exogenous sulfite ingestion

Sulfites whether ingested or produced through the sulfur-containing amino acids metabolism of the animal are very active molecules and can cause cellular toxicity. Sulfite oxidase (SOX), a heme- and molybdenum containing mitochondrial enzyme, prevents mammalian cells from adverse effects of sulfite toxicity by metabolizing sulfite to sulfate. The present study was aimed to investigate effect of sulfite on the N-methyl-(D)-aspartate (NMDA) receptor (NMDAR) NR2A and NR2B subunits in hippocampus of normal and SOX-deficient rats. Rats were divided into four groups; (1) control group, which was given rat chow and tap water ad libitum (C), (2) sulfite group, treated with sulfite (25 mg/kg) in drinking water and commercial rat chow ad libitum (S), (3) SOX-deficient group, maintained on high-W/Mo-deficient regimen to produce SOX deficiency (D), and (4) SOX-deficient + sulfite group (DS), prepared as those in the third group and were afterwards given sulfite (25 mg/kg) additionally. Whole treatment schedule were continued for 6 weeks. Sulfite treatment caused a decrease of NR2A and NR2B subunits of the NMDAR in hippocampus of rats in S and DS groups. Interestingly, similar decrement was observed in D group, probably due to increased endogen sulfite production. In summary, the results indicated that feeding sulfite to the rats may cause down-regulation of NMDARs by degrading NR2A and NR2B subunits of it, which may be considered as a neuro-compensatory mechanism

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. (Folia Histochemica et Cytobiologica 2012, Vol. 50, No. 2, 228-238)WoSScopu

The effects of docosahexaenoic acid on glial derived neurotrophic factor and neurturin in bilateral rat model of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder marked by cell death in the Substantia nigra (SN). Docosahexaenoic acid (DHA) is the major polyunsaturated fatty acid (PUFA) in the phospholipid fraction of the brain and is required for normal cellular function. Glial cell line derived neurotrophic factor (GDNF) and neurturin (NTN) are very potent trophic factors for PD. The aim of the study was to evaluate the neuroprotective effects of GDNF and NTN by investigating their immunostaining levels after administration of DHA in a model of PD. For this reason we hypothesized that DHA administration of PD might alter GDNF, NTN expression in SN. MPTP neurotoxin that induces dopaminergic neurodegeneration was used to create the experimental Parkinsonism model. Rats were divided into; control, DHA-treated (DHA), MPTP-induced (MPTP), MPTP-induced+DHA-treated (MPTP+DHA) groups. Dopaminergic neuron numbers were clearly decreased in MPTP, but showed an increase in MPTP+DHA group. As a result of this, DHA administration protected dopaminergic neurons as shown by tyrosine hydroxylase immunohistochemistry. In the MPTP+DHA group, GDNF, NTN immunoreactions in dopaminergic neurons were higher than that of the MPTP group. In conclusion, the characterization of GDNF and NTN will certainly help elucidate the mechanism of DHA action, and lead to better strategies for the use of DHA to treat neurodegenerative diseases