open access

Vol 56, No 1 (2018)
Original paper
Submitted: 2017-08-01
Accepted: 2018-03-09
Published online: 2018-03-22
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Neuronal nitric oxide synthase phosphorylation induced by docosahexaenoic acid protects dopaminergic neurons in an experimental model of Parkinson’s disease

Hande Parlak1, Ayse Ozkan1, Sayra Dilmac2, Gamze Tanriover2, Ozlem Ozsoy1, Aysel Agar1
·
Pubmed: 29577226
·
Folia Histochem Cytobiol 2018;56(1):27-37.
Affiliations
  1. Akdeniz University, Faculty of Medicine, Department of Physiology, Antalya, Turkey
  2. Akdeniz University, Faculty of Medicine, Department of Histology and Embryology, Antalya, Turkey, Antalya, Türkiye

open access

Vol 56, No 1 (2018)
ORIGINAL PAPERS
Submitted: 2017-08-01
Accepted: 2018-03-09
Published online: 2018-03-22

Abstract

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 mice
were 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 gavage
for four weeks. Motor activity of the mice was evaluated with pole, locomotor activity and rotarod tests. Caspase-3
activity, 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 and
phospho-nNOS (p-nNOS) in SN.
Results. An increased return and total down time in the MPTP group was observed in the pole test, while DHA
treatment decreased both parameters. The ambulatory activity, total distance and total locomotor activities were
decreased in the MPTP group, whereas they were increased by DHA treatment. MPTP-treated animals exhibited
shorter time on the rod test which was significantly increased by DHA treatment. DHA administration significantly
decreased 4-HNE and nitrate/nitrite levels of SN supernatants and protected the TH (+) dopaminergic
neurons of SN in the DHA + MPTP group compared to the MPTP group. DHA treatment significantly decreased
nNOS 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 increasing
nNOS serine 852 phosphorylation in the experimental mice model of PD.

Abstract

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 mice
were 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 gavage
for four weeks. Motor activity of the mice was evaluated with pole, locomotor activity and rotarod tests. Caspase-3
activity, 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 and
phospho-nNOS (p-nNOS) in SN.
Results. An increased return and total down time in the MPTP group was observed in the pole test, while DHA
treatment decreased both parameters. The ambulatory activity, total distance and total locomotor activities were
decreased in the MPTP group, whereas they were increased by DHA treatment. MPTP-treated animals exhibited
shorter time on the rod test which was significantly increased by DHA treatment. DHA administration significantly
decreased 4-HNE and nitrate/nitrite levels of SN supernatants and protected the TH (+) dopaminergic
neurons of SN in the DHA + MPTP group compared to the MPTP group. DHA treatment significantly decreased
nNOS 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 increasing
nNOS serine 852 phosphorylation in the experimental mice model of PD.

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Keywords

Parkinson’s disease; mice; protection; MPTP; DHA; nNOS phosphorylation; lipid peroxidation; caspase-3

About this article
Title

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

Journal

Folia Histochemica et Cytobiologica

Issue

Vol 56, No 1 (2018)

Article type

Original paper

Pages

27-37

Published online

2018-03-22

Page views

5012

Article views/downloads

1956

DOI

10.5603/FHC.a2018.0005

Pubmed

29577226

Bibliographic record

Folia Histochem Cytobiol 2018;56(1):27-37.

Keywords

Parkinson’s disease
mice
protection
MPTP
DHA
nNOS phosphorylation
lipid peroxidation
caspase-3

Authors

Hande Parlak
Ayse Ozkan
Sayra Dilmac
Gamze Tanriover
Ozlem Ozsoy
Aysel Agar

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