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

(Z)-6-[(2-Fluorophenyliminio)methylene]2,3-dihydroxyphenolate

The title compound, C13H10FNO3, crystallizes in a zwitterionic form. The dihedral angle between the aromatic rings is 21.69 (9)degrees. O-H center dot center dot center dot O hydrogen bonds generate a centrosymmetric R-2(2)(10) dimer and the dimers are linked by O-H center dot center dot center dot O hydrogen bonds into sheets parallel to (10 (1) over bar)

(E)-4-[(4-chlorophenyl)diazenyl]-2-isopropylphenol

In the title compound, C15H15ClN2O, the aromatic rings adopt a trans configuration with respect to the N = N bond, as found for other diazene derivatives. The crystal structure is stabilized by intermolecular O - H center dot center dot center dot N hydrogen bonds, forming a polymeric chain along the c axis

Dimethyl 5-(3,4-dicyano-phenoxy)isophthalate

The crystal structure of the title compound, C18H12N2O5, is stabilized by inter-molecular C-HcO and pi-pi inter-actions

4,4 '-(4,4 '-Thiodiphenoxy)diphthalonitrile

The title compound, C28H14N4O2S, contains four aromatic rings, and the crystal structure is stabilized by pi-pi stacking

4-Diphenylmethoxyphthalonitrile

The title compound, C21H14N2O, contains three aromatic rings. The structure is stabilized by pi-pi stacking interactions

(E)-4-(p-Tolyldiazenyl)phenol

The title compound, C13H12N2O, consisting of two aromatic groups linked through a diazene bridge, exhibits trans geometry with respect to the azo double bond and deviates slightly from planarity. The crystal structure is stabilized by intermolecular O-H...N hydrogen bonds

Propyl 4-(3,4-dicyanophenoxy)benzoate

The title compound, C18H14N2O3, a phthalonitrile derivative, contains two aromatic rings, one of which carries two cyano groups. The crystal structure is stabilized by one intramolecular C-H center dot center dot center dot O and two intermolecular C-H center dot center dot center dot O hydrogen bonds

(E)-2-[(2-morpholinoethylimino)methyl]phenol

The title compound, C13H18N2O2, exists in the enol-imine tautomeric form with a strong intramolecular O-H center dot center dot center dot N hydrogen bond [O center dot center dot center dot N = 2.5795 (18) angstrom], and the morpholine ring adopts an almost perfect chair conformation

PM3 semiempirical study and its comparison with X-ray crystal structure of 4-[2-methyl-4-(4-methoxyphenylazo)] phenoxyphtalonitrile

The molecular and crystal structures of the title compound, C22H16N4O2, were determined by single crystal X-ray diffraction technique. The title compound crystallizes in monoclinic space group P1 2 (1) /n1, with a=12.7811(9) angstrom, b=8.2002(4) angstrom, c=17.8772(14) angstrom, Z=4, D (calc)=1.3112(1) g/cm(3), mu (Mo-K-alpha)=0.087 mm(-1). The structure was solved by direct methods and refined to a final R=0.056 for 1891 reflections with I > 2 sigma (I). The asymmetric unit in the crystal structure contains only one neutral molecule. The positions of nitrogen atoms in the azo groups were disordered. There is no classic hydrogen bond in the crystal structure. The molecules in the crystal structure are stacked by pi-pi stacking and one edge-to-face interactions. In order to determine conformational flexibility and crystal packing effects on the molecules, molecular energy profile of the title compound was obtained with respect to the selected torsion angle, which is varied from -180 degrees to +180 degrees in every 10 degrees via PM3 semi-empirical method