Microglia may compensate for dopaminergic neuron loss in experimental Parkinsonism through selective elimination of glutamatergic synapses from the subthalamic nucleus

Glia ◽  
2017 ◽  
Vol 65 (11) ◽  
pp. 1833-1847 ◽  
Author(s):  
Hitomi Aono ◽  
Mohammed Emamussalehin Choudhury ◽  
Hiromi Higaki ◽  
Kazuya Miyanishi ◽  
Yuka Kigami ◽  
...  
Keyword(s):  
Subthalamic Nucleus ◽  
Dopaminergic Neuron ◽  
Glutamatergic Synapses ◽  
Neuron Loss ◽  
Experimental Parkinsonism ◽  
Selective Elimination ◽  
Dopaminergic Neuron Loss

scholarly journals Norepinephrine depleting toxin DSP-4 and LPS alter gut microbiota and induce neurotoxicity in α-synuclein mutant mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sheng Song ◽  
Jie Liu ◽  
Feng Zhang ◽  
Jau-Shyong Hong
Keyword(s):  
Gene Expression ◽  
Gut Microbiota ◽  
Dopaminergic Neuron ◽  
Critical Role ◽  
Genetic Mutation ◽  
Clinical Findings ◽  
Translocator Protein ◽  
Substantia Nigra Pars Compacta ◽  
Neuron Loss ◽  
Dopaminergic Neuron Loss

Abstract This study examined the genetic mutation and toxicant exposure in producing gut microbiota alteration and neurotoxicity. Homozygous α-synuclein mutant (SNCA) mice that overexpress human A53T protein and littermate wild-type mice received a single injection of LPS (2 mg/kg) or a selective norepinephrine depleting toxin DSP-4 (50 mg/kg), then the motor activity, dopaminergic neuron loss, colon gene expression and gut microbiome were examined 13 months later. LPS and DSP-4 decreased rotarod and wirehang activity, reduced dopaminergic neurons in substantia nigra pars compacta (SNpc), and SNCA mice were more vulnerable. SNCA mice had 1,000-fold higher human SNCA mRNA expression in the gut, and twofold higher gut expression of NADPH oxidase (NOX2) and translocator protein (TSPO). LPS further increased expression of TSPO and IL-6 in SNCA mice. Both LPS and DSP-4 caused microbiome alterations, and SNCA mice were more susceptible. The altered colon microbiome approximated clinical findings in PD patients, characterized by increased abundance of Verrucomicrobiaceae, and decreased abundance of Prevotellaceae, as evidenced by qPCR with 16S rRNA primers. The Firmicutes/Bacteroidetes ratio was increased by LPS in SNCA mice. This study demonstrated a critical role of α-synuclein and toxins interactions in producing gut microbiota disruption, aberrant gut pro-inflammatory gene expression, and dopaminergic neuron loss.

scholarly journals Microbiome changes: an indicator of Parkinson’s disease?

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Caroline Haikal ◽  
Qian-Qian Chen ◽  
Jia-Yi Li
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gut Microbiome ◽  
Dopaminergic Neuron ◽  
Alpha Synuclein ◽  
Neuron Loss ◽  
The Future ◽  
Dopaminergic Neuron Loss

AbstractParkinson’s disease is characterized by dopaminergic neuron loss and intracellular inclusions composed mainly of alpha synuclein (α-syn), but the mechanism of pathogenesis is still obscure. In recent years, more attention has been given to the gut as a key player in the initiation and progression of PD pathology. Several studies characterizing changes in the microbiome, particularly the gut microbiome, have been conducted. Although many studies found a decrease in the bacterial family Prevotellaceae and in butyrate-producing bacterial genera such as Roseburia and Faecalibacteria, and an increase in the genera Akkermansia many of the studies reported contradictory findings. In this review, we highlight the findings from the different studies and reflect on the future of microbiome studies in PD research.

Risk factors for dopaminergic neuron loss in human α-synuclein transgenic mice

2004 ◽  
Vol 19 (4) ◽  
pp. 845-854 ◽  
Author(s):  
M. J. Thiruchelvam ◽  
J. M. Powers ◽  
D. A. Cory-Slechta ◽  
E. K. Richfield
Keyword(s):  
Risk Factors ◽  
Transgenic Mice ◽  
Dopaminergic Neuron ◽  
Neuron Loss ◽  
Dopaminergic Neuron Loss

scholarly journals Rapamycin activation of 4E-BP prevents parkinsonian dopaminergic neuron loss

2009 ◽  
Vol 12 (9) ◽  
pp. 1129-1135 ◽  
Author(s):  
Luke S Tain ◽  
Heather Mortiboys ◽  
Ran N Tao ◽  
Elena Ziviani ◽  
Oliver Bandmann ◽  
...  
Keyword(s):  
Dopaminergic Neuron ◽  
Neuron Loss ◽  
Dopaminergic Neuron Loss

scholarly journals Autophagic Impairment Contributes to Systemic Inflammation-Induced Dopaminergic Neuron Loss in the Midbrain

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e70472 ◽  
Author(s):  
Hui-Fen Zheng ◽  
Ya-Ping Yang ◽  
Li-Fang Hu ◽  
Mei-Xia Wang ◽  
Fen Wang ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
Dopaminergic Neuron ◽  
Neuron Loss ◽  
Dopaminergic Neuron Loss
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