HDAC6 Deficiency Has Moderate Effects on Behaviors and Parkinson’s Disease Pathology in Mice
Abstract
:1. Introduction
2. Results
2.1. The Construction Strategy and Validation of Hdac6−/− Mice
2.2. The Lack of HDAC6 Affects Animal Behaviors
2.3. The Lack of HDAC6 Does Not Affect the Contents of NE, DA and 5-HT in the Brain
2.4. HDAC6 Deficiency Slightly Alleviates the Motor Deficits Induced by MPTP
2.5. HDAC6 Deficiency Does Not Affect MPTP-Induced Changes of Monoamine Neurotransmitters in the Striatum of Mice
2.6. HDAC6 Deficiency Does Not Affect the MPTP-Induced Damages to the Nigrostriatal Pathway in Male Mice, but Attenuates the Depletion in Striatal TH Proteins in Female Mice
2.7. HDAC6 Depletion Does Not Influence MPTP-Induced Glial Activation
2.8. HDAC6 Deficiency Does Not Affect Inflammatory or Apoptotic Pathways in the Striatum of MPTP-Induced PD Mice
3. Discussion
4. Materials and Methods
4.1. Animals
4.2. MPTP Treatments of Mice
4.3. Pole Test
4.4. Rearing Test
4.5. Wire Hanging Test
4.6. Open Field Test (OFT)
4.7. Elevated Plus Maze Test (EPM)
4.8. Forced Swimming Test (FST)
4.9. High-Performance Liquid Chromatography (HPLC)
4.10. RNA Extraction and Quantitative Real-Time PCR
4.11. Protein Extraction and Western Blot
4.12. Immunofluorescence and Immunohistochemistry Staining
4.13. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
HDAC6 | Histone deacetylase 6 |
PD | Parkinson’s disease |
MPTP | 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine |
SNpc | Substantia nigra pars compacta |
PFC | Prefrontal cortex |
NAc | Nucleus accumbens |
Hip | Hippocampus |
Str | Striatum |
LBs | Lewy Bodies |
α-syn | α-synuclein |
UPS | Ubiquitin–proteasome system |
NES | Nuclear export signal |
SE14 | Ser-Glu-containing tetrapeptide |
NLS | Nuclear localization signal |
ZnF-UBP | Ubiquitin-binding zinc-finger |
Hsp90 | Heat shock proteins90 |
KO | HDAC6 deficiency |
WT | Wild-type |
OFT | Open field test |
EPM | Elevated plus maze |
FST | Forced swimming test |
TST | Tail suspension test |
5-HT | Serotonin |
5-HIAA | 5-hydroxyindoleacetic acid |
DA | Dopamine |
DOPAC | 3,4-dihydroxyphenylacetic acid |
NE | Norepinephrine |
IHC | Immunohistochemical staining |
IF | Immunofluorescence staining |
SDS-PAGE | Sodium dodecyl sulfate–polyacrylamide gel electrophoresis |
PVDF | Polyvinylidene fluoride |
Bcl-2 | B cell leukemia/lymphoma-2 |
Bax | Bcl-2-associated X |
BDNF | Brain-derived trophic factor |
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Zhao, J.; He, Y.; Duan, Y.; Ma, Y.; Dong, H.; Zhang, X.; Fang, R.; Zhang, Y.; Yu, M.; Huang, F. HDAC6 Deficiency Has Moderate Effects on Behaviors and Parkinson’s Disease Pathology in Mice. Int. J. Mol. Sci. 2023, 24, 9975. https://doi.org/10.3390/ijms24129975
Zhao J, He Y, Duan Y, Ma Y, Dong H, Zhang X, Fang R, Zhang Y, Yu M, Huang F. HDAC6 Deficiency Has Moderate Effects on Behaviors and Parkinson’s Disease Pathology in Mice. International Journal of Molecular Sciences. 2023; 24(12):9975. https://doi.org/10.3390/ijms24129975
Chicago/Turabian StyleZhao, Jiayin, Yongtao He, Yufei Duan, Yuanyuan Ma, Hongtian Dong, Xiaoshuang Zhang, Rong Fang, Yunhe Zhang, Mei Yu, and Fang Huang. 2023. "HDAC6 Deficiency Has Moderate Effects on Behaviors and Parkinson’s Disease Pathology in Mice" International Journal of Molecular Sciences 24, no. 12: 9975. https://doi.org/10.3390/ijms24129975