Dataset Information

HOTAIR drives autophagy in midbrain dopaminergic neurons in the substantia nigra compacta in a mouse model of Parkinson's disease by elevating NPTX2 via miR-221-3p binding.

ABSTRACT: Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive cell loss, largely confined to mesencephalic dopamine neurons of the substantia nigra. This study investigated the functional relevance of the HOX transcript antisense intergenic RNA (HOTAIR)/microRNA-221-3 (miR-221-3p)/neuronal pentraxin II (NPTX2) axis in the process of dopaminergic neuron autophagy using PD mouse models. The PD mouse models were established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP), while PD cell model was constructed by pretreatment with 1-methyl-4-phenylpyridinium (MPP+). The expression of HOTAIR was then examined using RT-qPCR. In addition, the interactions between HOTAIR, miR-221-3p, and NPTX2 were detected through RIP and dual-luciferase reporter gene assays. CCK-8 assay was performed to measure cell viability, and the expression of autophagy-related genes was determined using Western blot analysis. HOTAIR was found to be significantly expressed in the substantia nigra compact tissues and MN9D cells following PD modeling. HOTAIR could bind to miR-221-3p and elevate the NPTX2 expression, which resulted in diminished cell viability and enhanced autophagy of dopaminergic neurons both in vitro and in vivo. In summary, down-regulation of HOTAIR could potentially inhibit the autophagy of dopaminergic neurons in the substantia nigra compacta in a mouse model of PD, thus saving the demise of dopaminergic neurons.

SUBMITTER: Lang Y

PROVIDER: S-EPMC7244061 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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HOTAIR drives autophagy in midbrain dopaminergic neurons in the substantia nigra compacta in a mouse model of Parkinson's disease by elevating NPTX2 <i>via</i> miR-221-3p binding.

Lang Yue Y Li Yu Y Yu Haojia H Lin Lulu L Chen Xingchi X Wang Sainan S Zhang Hui H

Aging 20200512 9

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive cell loss, largely confined to mesencephalic dopamine neurons of the substantia nigra. This study investigated the functional relevance of the HOX transcript antisense intergenic RNA (HOTAIR)/microRNA-221-3 (miR-221-3p)/neuronal pentraxin II (NPTX2) axis in the process of dopaminergic neuron autophagy using PD mouse models. The PD mouse models were established by intraperitoneal injection of 1-methyl-4-phenyl-1 ...[more]

PMID: 32396526

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Project description:The neurotoxicity of paraquat dichloride (PQ) was assessed in two inbred strains of 9- or 16-week old male C57BL/6 mice housed in two different laboratories and compared to the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). PQ was administered by intraperitoneal injections; either once (20 mg/kg) or twice (10 mg/kg) weekly for 3 weeks, while MPTP-HCl was injected 4 times on a single day (20 mg/kg/dose). Brains were collected 8, 16, 24, 48, 96 or 168 hours after the last PQ treatment, and 48 or 168 hours after MPTP treatment. Dopamine neurons in the substantia nigra pars compacta (SNpc) were identified by antibodies to tyrosine hydroxylase (TH+) and microglia were identified using Iba-1 immunoreactivity. The total number of TH+ neurons and the number of resting and activated microglia in the SNpc at 168 hours after the last dose were estimated using model- or design-based stereology, with investigators blinded to treatment. In a further analysis, a pathologist, also blinded to treatment, evaluated the SNpc and/or striatum for loss of TH+ neurons (SNpc) or terminals (striatum), cell death (as indicated by amino cupric silver uptake, TUNEL and/or caspase 3 staining) and neuroinflammation (as indicated by Iba-1 and/or GFAP staining). PQ, administered either once or twice weekly to 9- or 16-week old mice from two suppliers, had no effect on the number of TH+ neurons or microglia in the SNpc, as assessed by two groups, each blinded to treatment, using different stereological methods. PQ did not induce neuronal cell loss or degeneration in the SNpc or striatum. Additionally, there was no evidence of apoptosis, microgliosis or astrogliosis. In MPTP-treated mice, the number of TH+ neurons in the SNpc was significantly decreased and the number of activated microglia increased. Histopathological assessment found degenerating neurons/terminals in the SNpc and striatum but no evidence of apoptotic cell death. MPTP activated microglia in the SNpc and increased the number of astrocytes in the SNpc and striatum.

Dataset Information

HOTAIR drives autophagy in midbrain dopaminergic neurons in the substantia nigra compacta in a mouse model of Parkinson's disease by elevating NPTX2 via miR-221-3p binding.

Publications

HOTAIR drives autophagy in midbrain dopaminergic neurons in the substantia nigra compacta in a mouse model of Parkinson's disease by elevating NPTX2 <i>via</i> miR-221-3p binding.

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