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

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 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.

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