scholarly journals 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

Aging ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 7660-7678 ◽  
Author(s):  
Yue Lang ◽  
Yu Li ◽  
Haojia Yu ◽  
Lulu Lin ◽  
Xingchi Chen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Mouse Model ◽  
Dopaminergic Neurons ◽  
Midbrain Dopaminergic Neurons

scholarly journals Representation of spontaneous movement by dopaminergic neurons is cell-type selective and disrupted in parkinsonism

2016 ◽  
Vol 113 (15) ◽  
pp. E2180-E2188 ◽  
Author(s):  
Paul D. Dodson ◽  
Jakob K. Dreyer ◽  
Katie A. Jennings ◽  
Emilie C. J. Syed ◽  
Richard Wade-Martins ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Dopaminergic Neuron ◽  
Striatal Dopamine ◽  
Cell Type ◽  
Spontaneous Movement ◽  
Midbrain Dopaminergic Neurons ◽  
Spontaneous Movements

Midbrain dopaminergic neurons are essential for appropriate voluntary movement, as epitomized by the cardinal motor impairments arising in Parkinson’s disease. Understanding the basis of such motor control requires understanding how the firing of different types of dopaminergic neuron relates to movement and how this activity is deciphered in target structures such as the striatum. By recording and labeling individual neurons in behaving mice, we show that the representation of brief spontaneous movements in the firing of identified midbrain dopaminergic neurons is cell-type selective. Most dopaminergic neurons in the substantia nigra pars compacta (SNc), but not in ventral tegmental area or substantia nigra pars lateralis, consistently represented the onset of spontaneous movements with a pause in their firing. Computational modeling revealed that the movement-related firing of these dopaminergic neurons can manifest as rapid and robust fluctuations in striatal dopamine concentration and receptor activity. The exact nature of the movement-related signaling in the striatum depended on the type of dopaminergic neuron providing inputs, the striatal region innervated, and the type of dopamine receptor expressed by striatal neurons. Importantly, in aged mice harboring a genetic burden relevant for human Parkinson’s disease, the precise movement-related firing of SNc dopaminergic neurons and the resultant striatal dopamine signaling were lost. These data show that distinct dopaminergic cell types differentially encode spontaneous movement and elucidate how dysregulation of their firing in early Parkinsonism can impair their effector circuits.

scholarly journals Altered Thalamocortical Signaling in a Mouse Model of Parkinson’s Disease

2020 ◽  
Author(s):  
Olivia K. Swanson ◽  
David Richard ◽  
Arianna Maffei
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Motor Cortex ◽  
Mouse Model ◽  
Dopaminergic Neurons ◽  
Primary Motor Cortex ◽  
Midbrain Dopaminergic Neurons ◽  
Cell Type Specific ◽  
Midbrain Dopamine ◽  
Motor Thalamus

AbstractActivation of the primary motor cortex (M1) is important for the execution of skilled movements and motor learning, and its dysfunction contributes to the pathophysiology of Parkinson’s disease (PD). A well accepted idea in PD research, albeit not tested experimentally, is that loss of midbrain dopamine leads to decreased activation of M1 by the motor thalamus (Mthal). Here, we report that midbrain dopamine loss reduced Mthal input in a laminar- and cell type-specific fashion and induced laminar-specific changes in intracortical synaptic transmission. As a result, M1 activation by Mthal was decreased, but M1 output was increased. Our results demonstrate that loss of midbrain dopaminergic neurons alters thalamocortical activation of M1, and provide novel insights into circuit mechanisms for motor cortex dysfunction in a mouse model of PD.

scholarly journals Therapeutic Potential of Magnetic Nanoparticle-Based Human Adipose-Derived Stem Cells in a Mouse Model of Parkinson’s Disease

2021 ◽  
Vol 22 (2) ◽  
pp. 654
Author(s):  
Ka Young Kim ◽  
Keun-A Chang
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Magnetic Nanoparticles ◽  
Substantia Nigra ◽  
Mouse Model ◽  
Magnetic Nanoparticle ◽  
Imaging System ◽  
Therapeutic Potential ◽  
Adipose Derived Stem Cells

Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra. Several treatments for PD have focused on the management of physical symptoms using dopaminergic agents. However, these treatments induce various adverse effects, including hallucinations and cognitive impairment, owing to non-targeted brain delivery, while alleviating motor symptoms. Furthermore, these therapies are not considered ultimate cures owing to limited brain self-repair and regeneration abilities. In the present study, we aimed to investigate the therapeutic potential of human adipose-derived stem cells (hASCs) using magnetic nanoparticles in a 6-hydroxydopamine (6-OHDA)-induced PD mouse model. We used the Maestro imaging system and magnetic resonance imaging (MRI) for in vivo tracking after transplantation of magnetic nanoparticle-loaded hASCs to the PD mouse model. The Maestro imaging system revealed strong hASCs signals in the brains of PD model mice. In particular, MRI revealed hASCs distribution in the substantia nigra of hASCs-injected PD mice. Behavioral evaluations, including apomorphine-induced rotation and rotarod performance, were significantly recovered in hASCs-injected 6-OHDA induced PD mice when compared with saline-treated counterparts. Herein, we investigated whether hASCs transplantation using magnetic nanoparticles recovered motor functions through targeted brain distribution in a 6-OHDA induced PD mice. These results indicate that magnetic nanoparticle-based hASCs transplantation could be a potential therapeutic strategy in PD.

Neuroprotective Effects of a GLP-2 Analogue in the MPTP Parkinson’s Disease Mouse Model

2021 ◽  
pp. 1-15
Author(s):  
Zijuan Zhang ◽  
Li Hao ◽  
Ming Shi ◽  
Ziyang Yu ◽  
Simai Shao ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Mouse Model ◽  
Neurodegenerative Disorder ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Expression Levels ◽  
Dual Agonist

Background: Glucagon-like peptide 2 (GLP-2) is a peptide hormone derived from the proglucagon gene expressed in the intestines, pancreas and brain. Some previous studies showed that GLP-2 improved aging and Alzheimer’s disease related memory impairments. Parkinson’s disease (PD) is a progressive neurodegenerative disorder, and to date, there is no particular medicine reversed PD symptoms effectively. Objective: The aim of this study was to evaluate neuroprotective effects of a GLP-2 analogue in the 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) PD mouse model. Methods: In the present study, the protease resistant Gly(2)-GLP-2 (50 nmol/kg ip.) analogue has been tested for 14 days by behavioral assessment, transmission electron microscope, immunofluorescence histochemistry, enzyme-linked immunosorbent assay and western blot in an acute PD mouse model induced by MPTP. For comparison, the incretin receptor dual agonist DA5-CH was tested in a separate group. Results: The GLP-2 analogue treatment improved the locomotor and exploratory activity of mice, and improved bradykinesia and movement imbalance of mice. Gly(2)-GLP-2 treatment also protected dopaminergic neurons and restored tyrosine hydroxylase expression levels in the substantia nigra. Gly(2)-GLP-2 furthermore reduced the inflammation response as seen in lower microglia activation, and decreased NLRP3 and interleukin-1β pro-inflammatory cytokine expression levels. In addition, the GLP-2 analogue improved MPTP-induced mitochondrial dysfunction in the substantia nigra. The protective effects were comparable to those of the dual agonist DA5-CH. Conclusion: The present results demonstrate that Gly(2)-GLP-2 can attenuate NLRP3 inflammasome-mediated inflammation and mitochondrial damage in the substantia nigra induced by MPTP, and Gly(2)-GLP-2 shows neuroprotective effects in this PD animal model.

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