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NEUROLOGY / EXPERIMENTAL RESEARCH
Inhibition of histone deacetylase promotes a neuroprotective mechanism in an experimental model of Parkinson’s disease
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
Submission date: 2020-09-18
Final revision date: 2020-10-18
Acceptance date: 2020-11-07
Online publication date: 2021-03-05
Corresponding author
Ying Wang
Department of Neurology, Second Affiliated Hospital of Kunming Medical University, Kunming , Yunnan , China , 650101 Tel&Fex: 0086-0871-65351281, China
Department of Neurology, Second Affiliated Hospital of Kunming Medical University, Kunming , Yunnan , China , 650101 Tel&Fex: 0086-0871-65351281, China
Arch Med Sci 2024;20(2):664-674
KEYWORDS
TOPICS
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.
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.
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