Exercise in an animal model of Parkinson’s disease: Motor recovery but not restoration of the nigrostriatal pathway

Churchill, Madeline J.; Pflibsen, Lacey R; Sconce, Michelle D; Moore, Cynthia; Kim, K.; Meshul, Charles K.

doi:10.1016/j.neuroscience.2017.07.031

Cited by 33 publications

(35 citation statements)

References 96 publications

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“…The MPTP and SD+MPTP groups received intraperitoneal injections of MPTP (Santa Cruz Biotechnology, Dallas, TX, USA) as described by Churchill et al (, ) for 5 days a week for 4 weeks, after 4 weeks of undergoing either sleep disruption or no sleep disruption (Figure ). The dosages of MPTP (calculated as the base, dissolved in normal saline) used in our progressive model consisted of 10 mg/kg/day (week 1, 5 d/wk), 20 mg/kg/day (week 2, 5 d/wk), 24 mg/kg/day (week 3, 5 d/wk), and 32 mg/kg/day (week 4, 5 d/wk).…”

Section: Methodsmentioning

confidence: 99%

“…The animals designated for IHC were first anesthetized with ketamine/xylazine and perfused transcardially with 6 ml of 1,000 units/ml of heparin (in 0.1 M phosphate buffer, pH 7.3), followed by 50 ml of 2.5% paraformaldehyde, 0.5% of glutaraldehyde, and 0.1% of picric acid. The brains were then cut coronally at the level of the hypothalamus and post‐fixed for 30 min in 2.5% of paraformaldehyde, 0.5% of glutaraldehyde, and 0.1% of picric acid using a microwave tissue processor (Pelco Biowave, Ted Pella Inc, Redding, CA, USA), as previously reported (Churchill et al, , ). The brains were then individually placed in scintillation vials containing 0.1 M PB at 4°C until IHC processing.…”

Section: Methodsmentioning

confidence: 99%

“…Animals from each of the four treatment groups (total n = 24) were used for IHC analysis. The fixed rostral half of the brain was sliced coronally using a vibratome (VT 1000S; Leica, Nussloch, Eisfield, Germany) at a thickness of 60 µm through the entire rostral‐caudal extent of the striatum to the level of the anterior commissure (anterior‐posterior from Bregma: +1.2 to +0.25 mm) as previously described (Churchill et al, ; Hood, Liguore, Moore, Pflibsen, & Meshul, ; Sconce, Churchill, Greene, & Meshul, ; Sconce, Churchill, Moore, & Meshul, ). The caudal half of the brain was sliced coronally at 40 µm through the entire rostral‐caudal extent of the substantia nigra pars compacta (SNpc) (anterior‐posterior from Bregma, −2.50 to −4.24 mm) and sections placed in serial order in 48‐well plates.…”

Section: Methodsmentioning

confidence: 99%

“…Six slices from each animal collected through the whole rostral‐caudal extent of the striatum and SNpc (every third slice) were used for immunolabeling with a monoclonal antibody raised against TH (Immunostar, 1:250, mouse monoclonal, #22941, AB_572268; Table ). All tissue was processed for IHC on the same day using the Biowave (Ted Pella, Redding, CA) as previously described (Churchill et al, ; Hood et al, ; Sconce, Churchill, Greene, et al, ; Sconce, Churchill, Moore, et al, ). Once processed for TH immunoreactivity (TH‐ir), the tissue was mounted onto gel‐coated slides and left to dry at room temperature overnight.…”

Section: Methodsmentioning

confidence: 99%

“…Striatal sections were coverslipped with Permount Mounting Medium (Fisher Scientific, Fair Lawn, NJ). SNpc sections were counterstained with cresyl violet (CV), as described by Churchill et al (, ), and then coverslipped similar to that of the striatal sections.…”

Section: Methodsmentioning

confidence: 99%

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Effects of sleep disruption on stress, nigrostriatal markers, and behavior in a chronic/progressive MPTP male mouse model of parkinsonism

Bohlen

Moore

et al. 2019

J of Neuroscience Research

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Sleep complaints are an early clinical symptom of neurodegenerative disorders. Patients with Parkinson's disease (PD) experience sleep disruption (SD). The objective of this study was to determine if preexisting, chronic SD leads to a greater loss of tyrosine hydroxylase (TH) within the striatum and the substantia nigra following chronic/progressive exposure with the neurotoxin, 1‐methyl‐2‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP). Male mice underwent chronic SD for 4 weeks, then injected with vehicle (VEH) or increasing doses of MPTP for 4 weeks. There was a significant decrease in the plasma corticosterone levels in the MPTP group, an increase in the SD group, and a return to the VEH levels in the SD+MPTP group. Protein expression levels for TH in the striatum (terminals) and substantia nigra pars compacta (dopamine [DA] cell counts) revealed up to a 78% and 38% decrease, respectively, in the MPTP and SD+MPTP groups compared to their relevant VEH and SD groups. DA transporter protein expression increased in the striatum in the MPTP versus VEH group and in the SN/midbrain between the SD+MPTP and the VEH group. There was a main effect of MPTP on various gait measures (e.g., braking) relative to the SD or VEH groups. In the SD+MPTP group, there were no differences compared to the VEH group. Thus, SD, prior to administration of MPTP, has effects on serum corticosterone and gait but more importantly does not potentiate greater loss of TH within the nigrostriatal pathway compared to the MPTP group, suggesting that in PD patients with SD, there is no exacerbation of the DA cell loss.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Effects of sleep disruption on stress, nigrostriatal markers, and behavior in a chronic/progressive MPTP male mouse model of parkinsonism

Bohlen

Moore

et al. 2019

J of Neuroscience Research

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Positive effects of running exercise on astrocytes in the medial prefrontal cortex in an animal model of depression

Huang

Xiao

Tang

et al. 2022

J of Comparative Neurology

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Depression is one of the most common mental illnesses and seriously affects all aspects of life. Running exercise has been suggested to prevent or alleviate the occurrence and development of depression; however, the underlying mechanisms of these effects remain unclear. Independent studies have indicated that astrocytes play essential roles and that the medial prefrontal cortex (mPFC) is an important brain region involved in the pathology underlying depression. However, it is unknown whether running exercise achieves antidepressant effects by affecting the number of astrocytes and glutamate transport function in the mPFC. Here, animal models of depression were established using chronic unpredictable stress (CUS), and depression-like behavior was assessed by the sucrose preference test. After successfully establishing the depression model, experimental animals performed running exercise. Glial fibrillary acidic protein-positive (GFAP + ) cell number in the mPFC was precisely quantified using immunohistochemical and stereological methods, and the densities of bromodeoxyuridine-positive (BrdU + ) and BrdU + /GFAP + cells in the mPFC were measured using a semiquantitative immunofluorescence assay. Changes in glutamate transporter gene expression in mPFC astrocytes were detected by mRNA sequencing and qRT-PCR. We found that running exercise reversed CUS-induced decreases in sucrose preference, increased astrocyte number and the density of newborn astrocytes, and reversed decreases in gene expression levels of GFAP, S100b, and the glutamate transporters GLT-1 and GLAST in the mPFC of CUS animals. These results suggested that changes in astrocyte number and glutamate transporter function may be potential meditators of the effects of running exercise in the treatment of depression.

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Shared cerebral metabolic pathology in non-transgenic animal models of Alzheimer's and Parkinson's disease

et al. 2020

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Parkinson's disease (PD) and Alzheimer's disease (AD) are the most common chronic neurodegenerative disorders, characterized by motoric dysfunction or cognitive decline in the early stage, respectively, but often by both symptoms in the advanced stage. Among underlying molecular pathologies that PD and AD patients have in common, more attention is recently paid to the central metabolic dysfunction presented as insulin resistant brain state (IRBS) and altered cerebral glucose metabolism, both also explored in animal models of these diseases. This review aims to compare IRBS and alterations in cerebral glucose metabolism in representative non-transgenic animal PD and AD models. The comparison is based on the selectivity of the neurotoxins which cause experimental PD and AD, towards the cellular membrane and intracellular molecular targets as well as towards the selective neurons/non-neuronal cells, and the particular brain regions. Mitochondrial damage and coexpression of insulin receptors, glucose transporter-2 and dopamine transporter on the membrane of particular neurons as well as astrocytes seem to be the key points which are further discussed in a context of alterations in insulin signalling in the brain and its interaction with dopaminergic transmission, particularly regarding the time frame of the experimental AD/ PD pathology appearance and the correlation with cognitive and motor symptoms. Such a perspective provides evidence on IRBS being a common underlying metabolic pathology and a contributor to neurodegenerative processes in representative non-transgenic animal PD and AD models, instead of being a direct cause of a particular neurodegenerative disorder.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Exercise in an animal model of Parkinson’s disease: Motor recovery but not restoration of the nigrostriatal pathway

Cited by 33 publications

References 96 publications

Effects of sleep disruption on stress, nigrostriatal markers, and behavior in a chronic/progressive MPTP male mouse model of parkinsonism

Effects of sleep disruption on stress, nigrostriatal markers, and behavior in a chronic/progressive MPTP male mouse model of parkinsonism

Positive effects of running exercise on astrocytes in the medial prefrontal cortex in an animal model of depression

Shared cerebral metabolic pathology in non-transgenic animal models of Alzheimer's and Parkinson's disease

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