scholarly journals Optogenetic Stimulation of the M2 Cortex Reverts Motor Dysfunction in a Mouse Model of Parkinson's Disease

2019 ◽  
Vol 39 (17) ◽  
pp. 3234-3248 ◽  
Author(s):  
Luiz Alexandre Viana Magno ◽  
Helia Tenza-Ferrer ◽  
Mélcar Collodetti ◽  
Matheus Felipe Guimarães Aguiar ◽  
Ana Paula Carneiro Rodrigues ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Motor Dysfunction ◽  
Optogenetic Stimulation ◽  
Stimulation Of

scholarly journals Optogenetic stimulation of the pre‐Bötzinger Complex and the control of breathing in a mouse model of Parkinson's disease

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Luiz Marcelo Oliveira Santos ◽  
Nathan A Baertsch ◽  
Thiago Santos Moreira ◽  
Ana Carolina Takakura ◽  
Jan‐Marino A Ramirez
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Control Of Breathing ◽  
Optogenetic Stimulation ◽  
Bötzinger Complex ◽  
Stimulation Of

Glatiramer Acetate Reverses Motor Dysfunction and the Decrease in Tyrosine Hydroxylase Levels in a Mouse Model of Parkinson's Disease

Neuroscience ◽  
2019 ◽  
Vol 414 ◽  
pp. 8-27 ◽  
Author(s):  
Madeline J. Churchill ◽  
Mark A. Cantu ◽  
Ella A. Kasanga ◽  
Cindy Moore ◽  
Michael F. Salvatore ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Tyrosine Hydroxylase ◽  
Mouse Model ◽  
Glatiramer Acetate ◽  
Motor Dysfunction

scholarly journals Optogenetic stimulation of glutamatergic neurons in the cuneiform nucleus controls locomotor movements in a mouse model of Parkinson’s disease

2021 ◽  
Author(s):  
Maxime Fougère ◽  
Cornelis Immanuel van der Zouwen ◽  
Joël Boutin ◽  
Kloé Neszvecsko ◽  
Philippe Sarret ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Mouse Model ◽  
Brain Stimulation ◽  
Glutamatergic Neurons ◽  
Cuneiform Nucleus ◽  
Locomotor Deficits ◽  
Deep Brain ◽  
Stimulation Of

ABSTRACTIn Parkinson’s disease (PD), the loss of midbrain dopaminergic cells results in severe locomotor deficits such a gait freezing and akinesia. Growing evidence indicates that these deficits can be attributed to decreased activity in the Mesencephalic Locomotor Region (MLR), a brainstem region controlling locomotion. Clinicians are exploring deep brain stimulation of the MLR as a treatment option to improve locomotor function. The results are variable, from modest to promising. However, within the MLR, clinicians have targeted the pedunculopontine nucleus exclusively, while leaving the cuneiform nucleus unexplored. To our knowledge, the effects of cuneiform nucleus stimulation have never been determined in parkinsonian conditions in any animal model. Here, we addressed this issue in a mouse model of Parkinson’s disease based on bilateral striatal injection of 6-hydroxydopamine (6-OHDA), which damaged the nigrostriatal pathway and decreased locomotor activity. We show that selective optogenetic stimulation of glutamatergic neurons in the cuneiform nucleus in mice expressing channelrhodopsin in a Cre-dependent manner in Vglut2-positive neurons (Vglut2-ChR2-EYFP mice) increased the number of locomotor initiations, increased the time spent in locomotion, and controlled locomotor speed. Using deep learning-based movement analysis, we found that limb kinematics of optogenetic-evoked locomotion in pathological conditions were largely similar to those recorded in freely moving animals. Our work identifies the glutamatergic neurons of the cuneiform nucleus as a potentially clinically relevant target to improve locomotor activity in parkinsonian conditions. Our study should open new avenues to develop targeted stimulation of these neurons using deep brain stimulation, pharmacotherapy or optogenetics.SIGNIFICANCE STATEMENTIn Parkinson’s disease, alleviating locomotor deficits is a challenge. Clinicians are exploring deep brain stimulation of the Mesencephalic Locomotor Region, a brainstem region controlling locomotion, but results are mixed. However, the best target in this region in Parkinson’s disease remains unknown. Indeed, this region which comprises the pedunculopontine and cuneiform nuclei, contains different cell types with opposing effects on locomotor output. Here, using a mouse model where midbrain dopaminergic cells were damaged by a neurotoxin, we demonstrate that optogenetic activation of glutamatergic neurons in the cuneiform nucleus increases locomotion, controls speed, and evokes limb movements similar to those observed during spontaneous locomotion in intact animals. Our study identifies a potentially clinically relevant target to improve locomotor function in Parkinson’s disease.

scholarly journals Neutral Sphingomyelinase Behaviour in Hippocampus Neuroinflammation of MPTP-Induced Mouse Model of Parkinson’s Disease and in Embryonic Hippocampal Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Samuela Cataldi ◽  
Cataldo Arcuri ◽  
Stéphane Hunot ◽  
François-Pierre Légeron ◽  
Carmen Mecca ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Dihydroxyvitamin D3 ◽  
Neutral Sphingomyelinase ◽  
Proliferation And Apoptosis ◽  
Rigid Molecule ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide ◽  
Stimulation Of

Neutral sphingomyelinase is known to be implicated in growth arrest, differentiation, proliferation, and apoptosis. Although previous studies have reported the involvement of neutral sphingomyelinase in hippocampus physiopathology, its behavior in the hippocampus during Parkinson’s disease remains undetected. In this study, we show an upregulation of inducible nitric oxide synthase and a downregulation of neutral sphingomyelinase in the hippocampus of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP-) induced mouse model of Parkinson’s disease. Moreover, the stimulation of neutral sphingomyelinase activity with vitamin 1,25-dihydroxyvitamin D3 reduces specifically saturated fatty acid sphingomyelin by making sphingomyelin a less rigid molecule that might influence neurite plasticity. The possible biological relevance of the increase of neutral sphingomyelinase in Parkinson’s disease is discussed.

scholarly journals Temporal evolution of inflammation and neurodegeneration with alpha-synuclein propagation in Parkinson’s disease mouse model

2021 ◽  
Author(s):  
Thuy Thi Lai ◽  
Yun Joong Kim ◽  
Phuong Thi Nguyen ◽  
Young Ho Koh ◽  
Tinh Thi Nguyen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Inflammatory Response ◽  
Mouse Model ◽  
Temporal Relationship ◽  
Temporal Evolution ◽  
Inflammatory Responses ◽  
Alpha Synuclein ◽  
Motor Dysfunction ◽  
Whole Brain

Abstract Alpha-synuclein (αSyn) propagation has been determined to play a key role in the pathomechanism of Parkinson’s disease (PD), but neurodegeneration and the involvement of inflammation in its pathologic progression are yet to be well understood with regard to temporal relationship. In this study, by means of PD mouse model injected with intrastriatal αSyn preformed fibril (PFF), the temporal evolution of αSyn propagation, inflammation, and neurodegeneration was explored in the perspective of the striatum and the whole brain. In the PFF-injected striatum, inflammatory responses including the microglia and astrocyte were activated at the earliest stage and reduced with time, and the phosphorylated form of αSyn accumulation increased behind it. Thereafter, the degeneration of striatal dopaminergic neurons became significant with the conspicuity of behavior phenotype. Similar pattern of forefront eruption of inflammation and following αSyn propagation was noted in the opposite striatum, which was not injected with PFF. Meanwhile, in analyzing the whole brain, inflammatory responses were determined to have activated at the earliest stage, and the soluble αSyn expression then increased concurrently. Inflammatory response decreased afterward, and the accumulation of the insoluble form of αSyn increased behind it. Our results suggested that the inflammatory response may precede the accumulation of the pathologic form of αSyn; thereafter, the neurodegeneration and motor dysfunction followed αSyn proliferation in PD mouse model. From this model, recognizing the temporal relationship between inflammation, αSyn propagation, and neurodegeneration may be helpful in establishing PD animal model and monitoring the effect of interventional therapy.

scholarly journals Anti-Inflammatory Effects of the Novel Barbiturate Derivative MHY2699 in an MPTP-Induced Mouse Model of Parkinson’s Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1855
Author(s):  
Seulah Lee ◽  
Yeon Ji Suh ◽  
Yujeong Lee ◽  
Seonguk Yang ◽  
Dong Geun Hong ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Cell Activation ◽  
Motor Dysfunction ◽  
Dopamine Neurons ◽  
Neuroprotective Effects ◽  
Glial Cell Activation ◽  
Anti Inflammatory ◽  
Neuroprotective Treatment

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders, and is caused by the death of dopamine neurons and neuroinflammation in the striatum and substantia nigra. Furthermore, the inflammatory response in PD is closely related to glial cell activation. This study examined the neuroprotective effects of the barbiturate derivative, MHY2699 [5-(4-hydroxy 3,5-dimethoxybenzyl)-2 thioxodihydropyrimidine-4,6(1H,5H)-dione] in a mouse model of PD. MHY2699 ameliorated MPP⁺-induced astrocyte activation and ROS production in primary astrocytes and inhibited the MPP⁺-induced phosphorylation of MAPK and NF-κB. The anti-inflammatory effects of MHY2699 in protecting neurons were examined in an MPTP-induced mouse model of PD. MHY2699 inhibited MPTP-induced motor dysfunction and prevented dopaminergic neuronal death, suggesting that it attenuated neuroinflammation. Overall, MHY2699 has potential as a neuroprotective treatment for PD.

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