Gulay Hacioglu

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

Parkinsons 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.

The influence and the mechanism of docosahexaenoic acid on a mouse model of Parkinson's disease.

This study aimed to investigate the effects of docosahexaenoic acid (DHA) on the oxidative stress that occurs in an experimental mouse model of Parkinsons disease (PD). An experimental model of PD was created by four intraperitoneal injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (4 × 20 mg/kg, at 12h intervals). Docosahexaenoic acid was given daily by gavage for 4 weeks (36 mg/kg/day). The motor activity of the mice was evaluated via the pole test, and the dopaminergic lesion was determined by immunohistochemical analysis for tyrosine hydroxylase (TH)-immunopositive cells. The activity of antioxidant enzymes in the brain were determined by spectrophotometric assays and the concentration of thiobarbituric acid-reactive substances (TBARS) were measured as an index of oxidative damage. The number of apoptotic dopaminergic cells significantly increased in MPTP-treated mice compared to controls. Although DHA significantly diminished the number of cell deaths in MPTP-treated mice, it did not improve the decreased motor activity observed in the experimental PD model. Docosahexaenoic acid significantly diminished the amount of cell death in the MPTP+DHA group as compared to the MPTP group. TBARS levels in the brain were significantly increased following MPTP treatment. Glutathione peroxidase (GPx) and catalase (CAT) activities of brain were unaltered in all groups. The activity of brain superoxide dismutase (SOD) was decreased in the MPTP-treated group compared to the control group, but DHA treatment did not have an effect on SOD activity in the MPTP+DHA group. Our current data show that DHA treatment exerts neuroprotective actions on an experimental mouse model of PD. There was a decrease tendency in brain lipid oxidation of MPTP mice but it did not significantly.

The effect of different hypertension models on active avoidance learning

This study tested the effects of different hypertension models on active avoidance learning in rats. Three-month-old male Wistar rats were divided randomly into six groups as follows: control (C), sham operated (sham), two kidney-one clip (2K-1C), one kidney-one clip (1K-1C), deoxycorticosterone-salt (DOCA), and N-omega-nitro-L-arginine-methyl ester (L-NAME) groups. Mean arterial blood pressures were significantly higher in four hypertensive groups compared with control and sham groups. The active avoidance training results indicated that hypertension state is associated with learning impairment. Thiobarbituric acid-reactive substances (TBARS) were determined as an indicator of lipid peroxidation in brain and hippocampus. Additionally, brain and hippocampus nitrite levels were studied.

THE EFFECT OF DIFFERENT HYPERTENSION MODELS ON VISUAL EVOKED POTENTIALS

Even though there is an abundance of information about the complications of hypertension, studies of its influence on visual evoked potentials (VEPs) are rare. In previous studies, it was pointed out that hypertension induces changes on VEPs. However, it has not yet been clarified which models of hypertension are more effective on VEPs. The aim of this study was to investigate this subject in rats. Animals were divided equally into six groups: control group (C), sham operated (Sham), two kidney-one clip (2K-1C), one kidney-one clip (lK-lC), deoxycorticosterone-salt (DOCA), and N-omega-nitro-L-arginine-methyl ester (L-NAME) groups. Mean arterial pressure was significantly higher in four hypertensive groups compared with control and sham groups, but there were no significant differences either among hypertensive groups or between sham and control groups. At the end of the experimental period, flash visual evoked potentials were recorded. The mean latencies of P1, N1, P2, N2, and P3 components were significantly prolonged in all hypertensive groups compared with the control and sham groups. The mean latencies of all VEPs components in the L-NAME group were longer than in the other hypertensive groups. Thiobarbituric acid-reactive substances (TBARS) were determined as an indicator of lipid peroxidation. Our data showed that hypertension caused a significant increase of lipid peroxidation in brain and retinal tissues. Additionally, plasma renin activity (PRA) was highest in the 2K-1C group and lowest in the DOCA group.

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 relationship between oxidative stress markers and visual evoked potentials in different hypertension models

OBJECTIVE We aimed to define the influence of different hypertension models on lipid peroxidation markers [conjugated dienes (CD) and thiobarbituric acid-reactive substances (TBARS)], antioxidant protection [paraoxonase-1 (PON1) activity] and visual evoked potential (VEP) changes in rats. METHODS The study was designed as four different hypertension models. Rats (n=84) were divided equally into six groups: Control group (C), Sham operated (Sham), Two kidney-one clip (2K-1C), One kidney-one clip (1K-1C), Deoxycorticosterone acetate (DOCA) and N-omega-nitro-L-arginine-methyl ester (L-NAME). Brain TBARS, serum lipids (total and lipoprotein bound cholesterols and triglycerides) CD and TBARS levels and PON1 activity were assayed. Comparisons were performed using ANOVA or Wilcoxon/Kruskal-Wallis tests. Pearson correlation and linear regression analysis were used to evaluate associations of independent predictors with hypertension. RESULTS Mean arterial pressure, brain and serum lipid peroxidation markers, VEP latencies were significantly higher in four hypertensive groups compared with control and sham groups (p<0.05). Compared with controls, PON1 activity was decreased in DOCA, 1K1C and L-NAME groups (p<0.05). Serum PON1 activity was negatively correlated with lipid peroxidation markers and VEPs. In terms of VEPs records linear regression analysis showed that changes in N2 (B=1.51±0.34; p<0.001), P1 (B=-1.71±0.28; p<0.001), P3 (B=0.54±0.14; p<0.001), serum TBARS levels (B=0.94±0.24; p<0.001) and PON1 activity (B=0.05±0.02; p<0.01) were independently associated with elevated blood pressure. CONCLUSION Lipid peroxidation measured in serum and brain was associated with increased electrophysiological alterations recorded as VEPs. This study might suggest that serum PON1 activity may be protective against brain and serum lipid peroxidation as well as electrophysiological alterations in the brain in different hypertension models.

The effect of sodium metabisulphite on active avoidance performance in hypercholesterolemic rats.

The purpose of this study was to investigate the effects of hypercholesterolemia and sulphite on active avoidance learning. Male Wistar rats were divided into eight groups as follows: Control (C), Sulphite (S), Vitamin E (E), Sulphite + Vitamin E (SE), Hypercholesterolemia (H), Hypercholesterolemia + Sulphite (HS), Hypercholesterolemia + Vitamin E (HE), and Hypercholesterolemia + Sulphite + Vitamin E (HSE). At the end of the experimental period, the serum cholesterol level (mean ± SD) was significantly higher in H group (111.5 ± 11.11 mg dL−1) as compared to C group (63.5 ± 4.9 mg dL−1). Levels of thiobarbituric acid reactive substances (TBARS) were increased in HS group as compared to C, H, and S groups. Vitamin E reduced TBARS levels in HSE group compared with HS group. Active avoidance results indicated that hypercholesterolemia was associated with learning impairment. Our data clearly revealed that the combination of hypercholesterolemia and sulphite results in exaggerated impairment of active avoidance. Vitamin E improved active avoidance in HSE group compared with HS group. Therefore, the synergistic effect of hypercholesterolemia and sulphite may be associated with a considerable health risk.

ROLE OF NITRIC OXIDE ON AGE-DEPENDENT ALTERATIONS: INVESTIGATION OF ELECTROPHYSIOLOGIC AND BIOCHEMICAL PARAMETERS

In this experiment 40 young (3 months) and 40 middle-age (12 months) Wistar rats were used as subjects. These animals were assigned to eight groups as: young control (YC), middle-age control (MC), young + L-arginine (YA), middle-age + L-arginine (MA), young + L-NAME (YN), middle-age + L-NAME (MN), young + vitamin E (YE), and middle-age + vitamin E (ME). While physiological solution was administered to control groups, 160 mg/kg/day L-arginine, 10 mg/kg/day L-NAME, and 25 mg/kg/day vitamin E were injected into the experimental groups. After eight weeks of treatment, visual-evoked potentials (VEPs) were recorded, and thiobarbituric acid reactive substances (TBARS) and nitrite levels were determined in all experimental groups. It was observed that brain TBARS and nitrite levels increased significantly with age. There were also significant increments in the brain TBARS levels of YN and MN groups with respect to their controls. Although brain TBARS levels in YA, MA, YE, and ME groups were found to be increased compared with their corresponding controls, they didn t reach statistically significant levels. Brain nitrite level was found to be significantly decreased in the MN group, but increased in the MA group compared with the MC group. However, vitamin E caused a significant decrement in brain nitrite levels of YE and ME groups with respect to their control groups. P1 in the YN group and P1, P2, and N2 components in the MN group were delayed with respect to their corresponding controls, yet there were no significant changes between other groups. Data obtained from amplitudes showed that P2N2 and N2P3 amplitudes were decreased significantly in MN and ME groups with respect to the MC group. However, there were no important changes in amplitudes of other groups.

The effect of sodium metabisulfite on visual evoked potentials in rats with hypercholesterolemia

This study aimed to investigate the effects of hypercholesterolemia on visual evoked potentials (VEPs) and sulfite additional effects. Rats were assigned as follows: control (C), sulfite (S), hypercholesterolemia (H), vitamin E (E), sulfite + vitamin E (SE), hypercholesterolemia + sulfite (HS), hypercholesterolemia + vitamin E (HE), and hypercholesterolemia + sulfite + vitamin E (HSE). Hypercholesterolemic diet led significant increase in plasma cholesterol levels of rats. Brain thiobarbituric acid reactive substances (TBARS) levels were significantly increased in S, E, SE, HE and HSE groups compared with C. TBARS levels were increased in HE and HSE groups as compared to HS group. Nitrite levels were decreased in S, SE, H, HS and HSE groups compared with C. Nitrite level was notably increased in the HE group compared with H group. Sulfite exposure prolonged N1 and P3 latencies of VEP in group S compared with C. Prolonged VEP latencies by sulfite were significantly decreased by vitamin E in SE group. Cholesterol rich diet increased VEP latencies in comparison with control latencies. Sulfite gave rise to an additional increase in P3 latency in HS group compared with H group. Vitamin E-treated animals had notably shortened latencies of VEP components in HE and HSE groups according to the H and HS groups, respectively.