Characterization of a new low‐dose 6‐hydroxydopamine model of Parkinson's disease in rat

Gadelha-Filho

Oxidative Medicine and Cellular Longevity

et al. 2017

Parkinson's disease (PD), a progressive neurological pathology, presents motor and nonmotor impairments. The objectives were to support data on exercise benefits to PD. Male Wistar rats were distributed into sham-operated (SO) and 6-OHDA-lesioned, both groups without and with exercise. The animals were subjected to treadmill exercises (14 days), 24 h after the stereotaxic surgery and striatal 6-OHDA injection. Those from no-exercise groups stayed on the treadmill for the same period and, afterwards, were subjected to behavioral tests and euthanized for neurochemical and immunohistochemical assays. The data, analyzed by ANOVA and Tukey post hoc test, were considered significant for p < 0.05. The results showed behavioral change improvements in the 6-OHDA group, after the treadmill exercise, evaluated by apomorphine rotational behavior, open field, and rota rod tests. The exercise reduced striatal dopaminergic neuronal loss and decreased the oxidative stress. In addition, significant increases in BDNF contents and in immunoreactive cells to TH and DAT were also observed, in striata of the 6-OHDA group with exercise, relatively to those with no exercise. We conclude that exercise improves behavior and dopaminergic neurotransmission in 6-OHDA-lesioned animals. The increased oxidative stress and decreased BDNF contents were also reversed, emphasizing the importance of exercise for the PD management.

Section: Methodsmentioning

confidence: 99%

The Treadmill Exercise Protects against Dopaminergic Neuron Loss and Brain Oxidative Stress in Parkinsonian Rats

Gadelha-Filho

Oxidative Medicine and Cellular Longevity

et al. 2017

“…Stereology, however, is timeconsuming and often requires a specialized microscope and software for efficient and unbiased counting. New computational methods have enhanced counting, e.g., implementing MatLab in calculations provide similar results as obtained with the optical fractionator unbiased counting (Penttinen et al, 2016). However, this still requires manual labor, and newer methods aim to automatize counting.…”

Section: Quantification Of Dopaminergic Neurites and Cell Bodiesmentioning

confidence: 98%

“…These parameters have since been further optimized by others for further stability (Heuer, Smith, Lelos, Lane, & Dunnett, 2012;Penttinen et al, 2016). Comparing various dosing regimens, needles, and injection sites, we have found that the most reliable partial lesion and behavioral effect, analyzed by TH staining and drug-induced rotations, was obtained by injecting 3 × 2 μg of 6-OHDA into three regions of the striatum of rats (Penttinen et al, 2016). This low-dose model produces consistent lesions, and therefore, reduces the number of animals needed for experiments.…”

Section: Of 33mentioning

confidence: 99%

“…The advantages of the unilateral striatal 6-OHDA model, however, are that it replicates the degeneration of the nigrostriatal tract and this effect is quite reproducible and well-tolerated by the animals (Penttinen et al, 2016). The effects on locomotion can also be quantified reliably so it is very useful in screening for new therapeutics aimed at restoring or protecting the mesencephalic dopamine system (Penttinen, Parkkinen, Voutilainen, et al, 2018;Voutilainen et al, 2017).…”

Section: Of 33mentioning

confidence: 99%

See 1 more Smart Citation

Back and to the Future: From Neurotoxin‐Induced to Human Parkinson's Disease Models

et al. 2020

Self Cite

Parkinson's disease (PD) is an age‐related neurodegenerative disorder characterized by motor symptoms such as tremor, slowness of movement, rigidity, and postural instability, as well as non‐motor features like sleep disturbances, loss of ability to smell, depression, constipation, and pain. Motor symptoms are caused by depletion of dopamine in the striatum due to the progressive loss of dopamine neurons in the substantia nigra pars compacta. Approximately 10% of PD cases are familial arising from genetic mutations in α‐synuclein, LRRK2, DJ‐1, PINK1, parkin, and several other proteins. The majority of PD cases are, however, idiopathic, i.e., having no clear etiology. PD is characterized by progressive accumulation of insoluble inclusions, known as Lewy bodies, mostly composed of α‐synuclein and membrane components. The cause of PD is currently attributed to cellular proteostasis deregulation and mitochondrial dysfunction, which are likely interdependent. In addition, neuroinflammation is present in brains of PD patients, but whether it is the cause or consequence of neurodegeneration remains to be studied. Rodents do not develop PD or PD‐like motor symptoms spontaneously; however, neurotoxins, genetic mutations, viral vector‐mediated transgene expression and, recently, injections of misfolded α‐synuclein have been successfully utilized to model certain aspects of the disease. Here, we critically review the advantages and drawbacks of rodent PD models and discuss approaches to advance pre‐clinical PD research towards successful disease‐modifying therapy. © 2020 The Authors.

“…In the current study, we first counted the number of astrocytes by FindMyCell, Ilastik, custom thresholdbased script 20 and ImageJ in randomly selected sections from the brains of control and morphine-treated animals described by Jokinen 26 . Thus, we compared the performance of FindMyCells to semi-automated tools based on both machine-learning principles and manual thresholding.…”

Section: Introductionmentioning

confidence: 99%

A deep convolutional neural network approach for astrocyte detection

Suleymanova

Balassa

Tripathi

et al. 2017

Preprint

Self Cite

Astrocytes are involved in brain pathologies such as trauma or stroke, neurodegenerative disorders like Alzheimer's and Parkinson's disease, chronic pain, and many others. Determining cell density and timing of morphological and biochemical changes is important for a proper understanding of the role of astrocytes in physiological and pathological conditions. One of the most important of such analyses is astrocytes count within a complex tissue environment in microscopy images. The most widely used approaches for the quantification of microscopy images data are either manual stereological cell counting or semi-automatic segmentation techniques. Detecting astrocytes automatically is a highly challenging computational task, for which we currently lack efficient image analysis tools. In this study, we developed a fast and fully automated software that assesses the number of astrocytes using Deep Convolutional Neural Networks (DCNN). The method highly outperforms state-of-the-art image analysis and machine learning methods and provides detection accuracy and precision comparable to that of human experts. Additionally, the runtime of cell detection is significantly less than other three analyzed computational methods, and it is faster than human observers by orders of magnitude. We applied DCNN-based method to examine the number of astrocytes in different brain regions of rats with opioid-induced hyperalgesia/tolerance (OIH/OIT) as morphine tolerance is believed to activate glial cells in the brain. We observed strong positive correlation between manual cell detection and DCNN-based analysis method for counting astrocytes in the brains of experimental animals.