RESEARCH PAPER
Inhibition of histone deacetylase promotes
a neuroprotective mechanism in an experimental
model of Parkinson’s disease
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1 |
Department of Geriatrics, Chengdu Eighth People’s Hospital (Geriatric Hospital
of Chengdu Medical College), Chengdu, Sichuan, China |
2 |
Department of Neurosurgery, Second Affiliated Hospital of Kunming Medical
University, Kunming, Yunnan, China |
3 |
Department of Reproductive and Genetics, Second Affiliated Hospital of Kunming
Medical University, Kunming, Yunnan, China |
4 |
Talent Services Section, Chengdu Talent Service Centre for Healthcare Professionals,
Chengdu, Sichuan, China |
5 |
Department of Physical Examination, Chengdu First People’s Hospital, Chengdu,
Sichuan, China |
6 |
Department of Neurology, Second Affiliated Hospital of Kunming Medical University,
Kunming, Yunnan, China |
CORRESPONDING AUTHOR
Ying Wang
Department of Neurology, Second Affiliated Hospital of Kunming Medical University, Kunming , Yunnan , China , 650101
Tel&Fex: 0086-0871-65351281, China
Submission date: 2020-09-18
Final revision date: 2020-10-18
Acceptance date: 2020-11-07
Online publication date: 2021-03-05
KEYWORDS
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ABSTRACT
Introduction:
Therapies targeting histone deacetylase (HDAC) have gained
wider attention in the treatment of various clinical conditions. However, the
use of HDAC inhibitors in pre-clinical trials in the case of Parkinson’s disease
(PD) is very limited. In the present study, the HDAC inhibitor, entinostat, was
tested in animals induced with Parkinson’s disease experimentally.
Material and methods:
Wistar male rats (150 ±10 g) were administered
with rotenone (2 mg/kg/day, s.c.) for 21 days to induce PD, while entinostat
(20 mg/kg) was given intraperitoneally. Then, the neurological functions, PD
markers, and HDACs were analysed in the control and experimental animals.
Results:
The results demonstrated that rats that received entinostat displayed progressive motor, behavioural, and neurological function with attenuated α-synuclein and improved tyrosine-hydroxylase compared to control
cells. Moreover, the induction of PD in rats demonstrated reduced levels of
H2S, dopamine, 3, and 4-dihydroxyphenylacetic acid (DOPAC), and increased
monoamine oxidase activity in PD rats. However, the rats that received entinostat demonstrated progressive levels of dopa and DOPAC, with attenuated
levels of HDAC-2, -4, and -6 mRNA in the PD rats compared to controls. On
the other hand, elevated (p < 0.01) levels of PD marker genes such as GDF3
and NMDA2b were reduced, with a significant increase in neuroprotective
genes such as VDAC3 and CBX5 in entinostat-supplemented rats.
Conclusions:
The study results suggest that inhibition of HDAC systematically improves the neurological functions, and hence treatments, emphasizing that HDACI, as the speculated mechanism, will be a promising mode of
treatment in PD.