scholarly journals Histological Correlates of Neuroanatomical Changes in a Rat Model of Levodopa-Induced Dyskinesia Based on Voxel-Based Morphometry

2021 ◽  
Vol 13 ◽  
Author(s):  
Xiaoqian Zhang ◽  
Wei Chen ◽  
Yi Wu ◽  
Weiqi Zeng ◽  
Yuhao Yuan ◽  
...  
Keyword(s):  
Rat Model ◽  
Structural Changes ◽  
Piriform Cortex ◽  
Structural Mri ◽  
Cellular Level ◽  
Term Therapy ◽  
Voxel Based Morphometry ◽  
Dorsolateral Striatum ◽  
Synaptic Ultrastructure ◽  
6 Hydroxydopamine

Long-term therapy with levodopa (L-DOPA) in patients with Parkinson’s disease (PD) often triggers motor complications termed as L-DOPA-induced dyskinesia (LID). However, few studies have explored the pathogenesis of LID from the perspective of neuroanatomy. This study aimed to investigate macroscopic structural changes in a rat model of LID and the underlying histological mechanisms. First, we established the hemiparkinsonism rat model through stereotaxic injection of 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle, followed by administration of saline (PD) or L-DOPA to induce LID. Magnetic resonance imaging (MRI) and behavioral evaluations were performed at different time points. Histological analysis was conducted to assess the correlations between MRI signal changes and cellular contributors. Voxel-based morphometry (VBM) analysis revealed progressive bilateral volume reduction in the cortical and subcortical areas in PD rats compared with the sham rats. These changes were partially reversed by chronic L-DOPA administration; moreover, there was a significant volume increase mainly in the dorsolateral striatum, substantia nigra, and piriform cortex of the lesioned side compared with that of PD rats. At the striatal cellular level, glial fibrillary acidic protein-positive (GFAP+) astrocytes were significantly increased in the lesioned dorsolateral striatum of PD rats compared with the intact side and the sham group. Prolonged L-DOPA treatment further increased GFAP levels. Neither 6-OHDA damage nor L-DOPA treatment influenced the striatal expression of vascular endothelial growth factor (VEGF). Additionally, there was a considerable increase in synapse-associated proteins (SYP, PSD95, and SAP97) in the lesioned striatum of LID rats relative to the PD rats. Golgi-Cox staining analysis of the dendritic spine morphology revealed an increased density of dendritic spines after chronic L-DOPA treatment. Taken together, our findings suggest that striatal volume changes in LID rats involve astrocyte activation, enrichment of synaptic ultrastructure and signaling proteins in the ipsilateral striatum. Meanwhile, the data highlight the enormous potential of structural MRI, especially VBM analysis, in determining the morphological phenotype of rodent models of LID.

scholarly journals Structural Changes Observed in the Piriform Cortex in a Rat Model of Pre-motor Parkinson’s Disease

2018 ◽  
Vol 12 ◽  
Author(s):  
Marco Sancandi ◽  
Emma Victoria Schul ◽  
Georgia Economides ◽  
Andrew Constanti ◽  
Audrey Mercer
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rat Model ◽  
Structural Changes ◽  
Piriform Cortex

scholarly journals Characterization of the resting-state brain network topology in the 6-hydroxydopamine rat model of Parkinson’s disease

PLoS ONE ◽  
2017 ◽  
Vol 12 (3) ◽  
pp. e0172394 ◽  
Author(s):  
Robert Westphal ◽  
Camilla Simmons ◽  
Michel B. Mesquita ◽  
Tobias C. Wood ◽  
Steve C. R. Williams ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Network Topology ◽  
Rat Model ◽  
Resting State ◽  
Brain Network ◽  
6 Hydroxydopamine

Resveratrol attenuates 6-hydroxydopamine-induced oxidative damage and dopamine depletion in rat model of Parkinson's disease

2010 ◽  
Vol 1328 ◽  
pp. 139-151 ◽  
Author(s):  
Mohd.Moshahid Khan ◽  
Ajmal Ahmad ◽  
Tauheed Ishrat ◽  
M. Badruzzaman Khan ◽  
Md. Nasrul Hoda ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Oxidative Damage ◽  
Rat Model ◽  
Dopamine Depletion ◽  
6 Hydroxydopamine

The 6-hydroxydopamine Rat Model of Parkinson's Disease

10.3791/62923 ◽  
2021 ◽  
Author(s):  
Rayanne Poletti Guimarães ◽  
Danilo Leandro Ribeiro ◽  
Keila Bariotto dos Santos ◽  
Lívea Dornela Godoy ◽  
Mirella Rosine Corrêa ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rat Model ◽  
6 Hydroxydopamine

scholarly journals Extensive exploration of a novel rat model of Parkinson's disease using partial 6-hydroxydopamine lesion of dopaminergic neurons suggests new therapeutic approaches

Synapse ◽  
2018 ◽  
Vol 73 (3) ◽  
pp. e22077 ◽  
Author(s):  
Steven Vetel ◽  
Sophie Sérrière ◽  
Johnny Vercouillie ◽  
Jackie Vergote ◽  
Gabrielle Chicheri ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rat Model ◽  
Dopaminergic Neurons ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
6 Hydroxydopamine

Functional medial thickening and folding of the internal elastic lamina in coronary spasm

2011 ◽  
Vol 300 (2) ◽  
pp. H423-H430 ◽  
Author(s):  
Yasumi Uchida ◽  
Yasuto Uchida ◽  
Akimasa Matsuyama ◽  
Atsushi Koga ◽  
Yuko Maezawa ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Structural Changes ◽  
Light And Electron Microscopy ◽  
Coronary Spasm ◽  
Cellular Level ◽  
Internal Elastic Lamina ◽  
Circular Smooth Muscle ◽  
The Media ◽  
Medial Thickening ◽  
Elastic Lamina

Although there are a number of studies on vasospastic angina, the structural changes at the cellular level that occur in the coronary arterial wall during spasm are not well known. Coronary spasm was induced by brushing the coronary adventitia in nine anesthetized beagles, and structural changes in the spastic coronary segments were examined by light and electron microscopy, making comparisons with the adjacent nonspastic segments. The % diameter stenosis of the spastic segments as measured angiographically was 79.4 ± 12% (mean ± SD). Light microscopic changes in the spastic and nonspastic segments were as follows: medial thickness 1,512 vs. 392 μm ( P < 0.0001) and % diameter and % area stenoses of spastic segment 81.0% and 96.5%, respectively, indicating that spasm was induced by medial thickening. Circular smooth muscle cells (SMCs) in the media were arranged in parallel with the internal (IEL) and external (EEL) elastic lamina in nonspastic segments but radially rearranged in spastic segments. SMCs were classified by their patterns of connection to IEL into six types by electron microscopy. Of these, three contracted and pulled the IEL toward the EEL, causing folding of the IEL and waving of EEL resulting in thickening of the media and narrowing of the lumen. We conclude that coronary spasm was elicited by radial rearrangement of the medial SMCs due to their own contraction and resultant medial thickening and folding of IEL, creating a piston effect to narrow the lumen, i.e., spasm.

Mildronate as a Regulator of Protein Expression in a Rat Model of Parkinson’s Disease

Medicina ◽  
2011 ◽  
Vol 47 (10) ◽  
pp. 79 ◽  
Author(s):  
Sergejs Isajevs ◽  
Darja Isajeva ◽  
Ulrika Beitnere ◽  
Baiba Jansone ◽  
Ivars Kalvinsh ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Growth Factor ◽  
Substantia Nigra ◽  
Rat Model ◽  
Control Group ◽  
Western Blot Assay ◽  
Neural Cell Adhesion ◽  
6 Hydroxydopamine ◽  
Cardioprotective Drug

Background. Mildronate (3-[2,2,2-trimethylhydrazinium] propionate dihydrate) traditionally is a well-known cardioprotective drug. However, our recent studies convincingly demonstrated its neuroprotective properties. The aim of the present study was to evaluate the influence of mildronate on the expression of proteins that are involved in the differentiation and survival of the nigrostriatal dopaminergic neurons in the rat model of Parkinson’s disease (PD). The following biomarkers were used: heat shock protein 70 (Hsp70, a molecular chaperone), glial cell line-derived nerve growth factor (GDNF, a growth factor promoting neuronal differentiation, regeneration, and survival), and neural cell adhesion molecule (NCAM). Material and Methods. PD was modeled by 6-hydroxydopamine (6-OHDA) unilateral intrastriatal injection in rats. Mildronate was administered at doses of 10, 20, and 50 mg/kg for 2 weeks intraperitoneally before 6-OHDA injection. Rat brains were dissected on day 28 after discontinuation of mildronate injections. The expression of biomarkers was assessed immunohistochemically and by Western blot assay. Results. 6-OHDA decreased the expression of Hsp70 and GDNF in the lesioned striatum and substantia nigra, whereas in mildronate-pretreated (20 and 50 mg/kg) rats, the expression of Hsp70 and GDNF was close to the control group values. NCAM expression also was decreased by 6-OHDA in the striatum and it was totally protected by mildronate at a dose of 50 mg/kg. In contrast, in the substantia nigra, 6-OHDA increased the expression of NCAM, while mildronate pretreatment (20 and 50 mg/kg) reversed the 6-OHDA-induced overexpression of NCAM close to the control values. Conclusion. The obtained data showed that mildronate was capable to regulate the expression of proteins that play a role in the homeostasis of neuro-glial processes.

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