scholarly journals Engaging cognitive circuits to promote motor recovery in degenerative disorders. exercise as a learning modality

2016 ◽  
Vol 52 (1) ◽  
pp. 35-51 ◽  
Author(s):  
Michael W. Jakowec ◽  
Zhou Wang ◽  
Daniel Holschneider ◽  
Jeff Beeler ◽  
Giselle M. Petzinger
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Wide Spectrum ◽  
Disease Onset ◽  
Short Review ◽  
Motor Recovery ◽  
Adult Brain ◽  
Brain Disorders ◽  
Dopamine Depletion

AbstractExercise and physical activity are fundamental components of a lifestyle essential in maintaining a healthy brain. This is primarily due to the fact that the adult brain maintains a high degree of plasticity and activity is essential for homeostasis throughout life. Plasticity is not lost even in the context of a neurodegenerative disorder, but could be maladaptive thus promoting disease onset and progression. A major breakthrough in treating brain disorders such as Parkinson’s disease is to drive neuroplasticity in a direction to improve motor and cognitive dysfunction. The purpose of this short review is to present the evidence from our laboratories that supports neuroplasticity as a potential therapeutic target in treating brain disorders. We consider that the enhancement of motor recovery in both animal models of dopamine depletion and in patients with Parkinson’s disease is optimized when cognitive circuits are engaged; in other words, the brain is engaged in a learning modality. Therefore, we propose that to be effective in treating Parkinson’s disease, physical therapy must employ both skill-based exercise (to drive specific circuits) and aerobic exercise (to drive the expression of molecules required to strengthen synaptic connections) components to select those neuronal circuits, such as the corticostriatal pathway, necessary to restore proper motor and cognitive behaviors. In the wide spectrum of different forms of exercise, learning as the fundamental modality likely links interventions used to treat patients with Parkinson’s disease and may be necessary to drive beneficial neuroplasticity resulting in symptomatic improvement and possible disease modification.

scholarly journals Peptide TFP5/TP5 derived from Cdk5 activator P35 provides neuroprotection in the MPTP model of Parkinson’s disease

2015 ◽  
Vol 26 (24) ◽  
pp. 4478-4491 ◽  
Author(s):  
BK. Binukumar ◽  
Varsha Shukla ◽  
Niranjana D. Amin ◽  
Philip Grant ◽  
M. Bhaskar ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Neuroprotective Effect ◽  
Selective Inhibition ◽  
Motor Dysfunction ◽  
Dopamine Neurons ◽  
Dopamine Depletion ◽  
Neuroprotective Effects

Parkinson’s disease (PD) is a chronic neurodegenerative disorder characterized by the loss of dopamine neurons in the substantia nigra, decreased striatal dopamine levels, and consequent extrapyramidal motor dysfunction. Recent evidence indicates that cyclin-dependent kinase 5 (Cdk5) is inappropriately activated in several neurodegenerative conditions, including PD. To date, strategies to specifically inhibit Cdk5 hyperactivity have not been successful without affecting normal Cdk5 activity. Previously we reported that TFP5 peptide has neuroprotective effects in animal models of Alzheimer’s disease. Here we show that TFP5/TP5 selective inhibition of Cdk5/p25 hyperactivation in vivo and in vitro rescues nigrostriatal dopaminergic neurodegeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP/MPP+) in a mouse model of PD. TP5 peptide treatment also blocked dopamine depletion in the striatum and improved gait dysfunction after MPTP administration. The neuroprotective effect of TFP5/TP5 peptide is also associated with marked reduction in neuroinflammation and apoptosis. Here we show selective inhibition of Cdk5/p25 ­hyperactivation by TFP5/TP5 peptide, which identifies the kinase as a potential therapeutic target to reduce neurodegeneration in Parkinson’s disease.

scholarly journals Machine Learning Prediction of Parkinson's Disease Onset and Subtype Using Germline Variants

2021 ◽  
Author(s):  
Saya R Dennis ◽  
Tanya Simuni ◽  
Yuan Luo
Keyword(s):  
Machine Learning ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Disease Onset ◽  
The United States ◽  
Machine Learning Algorithms ◽  
Progression Rate ◽  
High Importance ◽  
Germline Variants

Parkinson's Disease is the second most common neurodegenerative disorder in the United States, and is characterized by a largely irreversible worsening of motor and non-motor symptoms as the disease progresses. A prominent characteristic of the disease is its high heterogeneity in manifestation as well as the progression rate. For sporadic Parkinson's Disease, which comprises ~90% of all diagnoses, the relationship between the patient genome and disease onset or progression subtype remains largely elusive. Machine learning algorithms are increasingly adopted to study the genomics of diseases due to their ability to capture patterns within the vast feature space of the human genome that might be contributing to the phenotype of interest. In our study, we develop two machine learning models that predict the onset as well as the progression subtype of Parkinson's Disease based on subjects' germline mutations. Our best models achieved an ROC of 0.77 and 0.61 for disease onset and subtype prediction, respectively. To the best of our knowledge, our models present state-of-the-art prediction performances of PD onset and subtype solely based on the subjects' germline variants. The genes with high importance in our best-performing models were enriched for several canonical pathways related to signaling, immune system, and protein modifications, all of which have been previously associated with PD symptoms or pathogenesis. These high-importance gene sets provide us with promising candidate genes for future biomedical and clinical research.

scholarly journals Imaging of Substantia Nigra in Parkinson’s Disease: A Narrative Review

2021 ◽  
Vol 11 (6) ◽  
pp. 769
Author(s):  
Paola Feraco ◽  
Cesare Gagliardo ◽  
Giuseppe La Tona ◽  
Eleonora Bruno ◽  
Costanza D’angelo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Neurodegenerative Disorder ◽  
Wide Spectrum ◽  
Imaging Techniques ◽  
Pulse Sequences ◽  
Imaging Biomarkers ◽  
Mri Imaging ◽  
Subcortical Structures

Parkinson’s disease (PD) is a progressive neurodegenerative disorder, characterized by motor and non-motor symptoms due to the degeneration of the pars compacta of the substantia nigra (SNc) with dopaminergic denervation of the striatum. Although the diagnosis of PD is principally based on a clinical assessment, great efforts have been expended over the past two decades to evaluate reliable biomarkers for PD. Among these biomarkers, magnetic resonance imaging (MRI)-based biomarkers may play a key role. Conventional MRI sequences are considered by many in the field to have low sensitivity, while advanced pulse sequences and ultra-high-field MRI techniques have brought many advantages, particularly regarding the study of brainstem and subcortical structures. Nowadays, nigrosome imaging, neuromelanine-sensitive sequences, iron-sensitive sequences, and advanced diffusion weighted imaging techniques afford new insights to the non-invasive study of the SNc. The use of these imaging methods, alone or in combination, may also help to discriminate PD patients from control patients, in addition to discriminating atypical parkinsonian syndromes (PS). A total of 92 articles were identified from an extensive review of the literature on PubMed in order to ascertain the-state-of-the-art of MRI techniques, as applied to the study of SNc in PD patients, as well as their potential future applications as imaging biomarkers of disease. Whilst none of these MRI-imaging biomarkers could be successfully validated for routine clinical practice, in achieving high levels of accuracy and reproducibility in the diagnosis of PD, a multimodal MRI-PD protocol may assist neuroradiologists and clinicians in the early and differential diagnosis of a wide spectrum of neurodegenerative disorders.

scholarly journals Behavioral Tests in Neurotoxin-Induced Animal Models of Parkinson’s Disease

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 1007
Author(s):  
E. Maruthi Prasad ◽  
Shih-Ya Hung
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Models ◽  
Neurodegenerative Disorder ◽  
Mitochondrial Respiratory Chain ◽  
Current Treatment ◽  
Muscle Rigidity ◽  
Motor Symptoms ◽  
Dopamine Depletion ◽  
Pathologic Features

Currently, neurodegenerative diseases are a major cause of disability around the world. Parkinson’s disease (PD) is the second-leading cause of neurodegenerative disorder after Alzheimer’s disease. In PD, continuous loss of dopaminergic neurons in the substantia nigra causes dopamine depletion in the striatum, promotes the primary motor symptoms of resting tremor, bradykinesia, muscle rigidity, and postural instability. The risk factors of PD comprise environmental toxins, drugs, pesticides, brain microtrauma, focal cerebrovascular injury, aging, and hereditary defects. The pathologic features of PD include impaired protein homeostasis, mitochondrial dysfunction, nitric oxide, and neuroinflammation, but the interaction of these factors contributing to PD is not fully understood. In neurotoxin-induced PD models, neurotoxins, for instance, 6-hydroxydopamine (6-OHDA), 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-Methyl-4-phenylpyridinium (MPP+), paraquat, rotenone, and permethrin mainly impair the mitochondrial respiratory chain, activate microglia, and generate reactive oxygen species to induce autooxidation and dopaminergic neuronal apoptosis. Since no current treatment can cure PD, using a suitable PD animal model to evaluate PD motor symptoms’ treatment efficacy and identify therapeutic targets and drugs are still needed. Hence, the present review focuses on the latest scientific developments in different neurotoxin-induced PD animal models with their mechanisms of pathogenesis and evaluation methods of PD motor symptoms.

scholarly journals Olfaction and Colour Vision: What Can They Tell Us about Parkinson’s Disease?

2018 ◽  
Vol 119 (2-3) ◽  
pp. 85-96 ◽  
Author(s):  
Irene Dall’Antonia ◽  
Karel Šonka ◽  
Petr Dušek
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Colour Vision ◽  
Neurodegenerative Disorder ◽  
Disease Onset ◽  
Alpha Synuclein ◽  
Nerve Tissue ◽  
Clinical Markers ◽  
Motor Abnormalities ◽  
Non Motor Symptoms

Parkinson’s disease is a neurodegenerative disorder with the pathological accumulation of alpha synuclein in the brain and peripheral nerve tissue. Early stages of synucleinopathies, often present clinically with rapid eye movement (REM) sleep disorder (RBD). Clinical markers that indicate early progression from RBD to manifest synucleinopathies include abnormal dopamine transporter (DAT) imaging, motor and non-motor symptoms. Despite the high diagnostic strength of DAT imaging and motor abnormalities, they are not the earliest biomarkers. Non-motor signs of neurodegeneration such as colour vision and olfaction abnormalities are detectable by clinical examination as early as 20 years before disease onset. Detailed analysis of olfactory and colour vision dysfunction can provide valuable information regarding brain pathologies, further specifying clinical phenotypes, and giving clues to underlying pathophysiological mechanisms in Parkinson’s disease and related disorders.

scholarly journals Neuroprotective mechanisms of red clover and soy isoflavones in Parkinson’s disease models

2020 ◽  
Author(s):  
Aurélie de Rus Jacquet ◽  
Abeje Ambaw ◽  
Mitali Arun Tambe ◽  
Sin Ying Ma ◽  
Michael Timmers ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Trifolium Pratense ◽  
Neurodegenerative Disorder ◽  
Disease Onset ◽  
Red Clover ◽  
Antioxidant Response ◽  
Motor Dysfunction ◽  
Neuroprotective Effects ◽  
Dietary Polyphenols

AbstractParkinson’s disease (PD) is a neurodegenerative disorder characterized by nigrostriatal degeneration and the spreading of aggregated forms of the presynaptic protein α-synuclein (aSyn) throughout the brain. PD patients are currently only treated with symptomatic therapies, and strategies to slow or stop the progressive neurodegeneration underlying the disease’s motor and cognitive symptoms are greatly needed. The time between the first neurobiochemical alterations and the initial presentation of symptoms is thought to span several years, and early neuroprotective dietary interventions could delay the disease onset or slow PD progression. This study aimed at characterizing the neuroprotective effects of isoflavones, a class of dietary polyphenols found in soy products and in the medicinal plant red clover (Trifolium pratense). We found that isoflavone-rich extracts and individual isoflavones rescued the loss of dopaminergic neurons and the shortening of neurites in primary mesencephalic cultures exposed to two PD-related insults, the environmental toxin rotenone and an adenovirus encoding the A53T aSyn mutant. The extracts and individual isoflavones also activated the Nrf2-mediated antioxidant response in astrocytes via a mechanism involving inhibition of the ubiquitin-proteasome system, and they alleviated deficits in mitochondrial respiration. Furthermore, an isoflavone-enriched soy extract reduced motor dysfunction exhibited by rats lesioned with the PD-related neurotoxin 6-OHDA. These findings suggest that plant-derived isoflavones could serve as dietary supplements to delay PD onset in at-risk individuals and mitigate neurodegeneration in the brains of patients.

scholarly journals Nuclear and Mitochondrial Genome, Epigenome and Gut Microbiome: Emerging Molecular Biomarkers for Parkinson’s Disease

2021 ◽  
Vol 22 (18) ◽  
pp. 9839
Author(s):  
Gleyce Fonseca Cabral ◽  
Ana Paula Schaan ◽  
Giovanna C. Cavalcante ◽  
Camille Sena-dos-Santos ◽  
Tatiane Piedade de Souza ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Genome ◽  
Gut Microbiome ◽  
Neurodegenerative Disorder ◽  
Disease Onset ◽  
Clinical Signs ◽  
Genomic Variation ◽  
Increasing Demand ◽  
Based Medicine

Background: Parkinson’s disease (PD) is currently the second most common neurodegenerative disorder, burdening about 10 million elderly individuals worldwide. The multifactorial nature of PD poses a difficult obstacle for understanding the mechanisms involved in its onset and progression. Currently, diagnosis depends on the appearance of clinical signs, some of which are shared among various neurologic disorders, hindering early diagnosis. There are no effective tools to prevent PD onset, detect the disease in early stages or accurately report the risk of disease progression. Hence, there is an increasing demand for biomarkers that may identify disease onset and progression, as treatment-based medicine may not be the best approach for PD. Over the last few decades, the search for molecular markers to predict susceptibility, aid in accurate diagnosis and evaluate the progress of PD have intensified, but strategies aimed to improve individualized patient care have not yet been established. Conclusions: Genomic variation, regulation by epigenomic mechanisms, as well as the influence of the host gut microbiome seem to have a crucial role in the onset and progress of PD, thus are considered potential biomarkers. As such, the human nuclear and mitochondrial genome, epigenome, and the host gut microbiome might be the key elements to the rise of personalized medicine for PD patients.

scholarly journals O6E.4 Metabolome and exposome profiling: new opportunities to study risk factors for parkinson’s disease

2019 ◽  
Vol 76 (Suppl 1) ◽  
pp. A60.1-A60
Author(s):  
Susan Peters ◽  
Douglas Walker ◽  
Gary Miller ◽  
Marc Chadeau-Hyam ◽  
Paolo Vineis ◽  
...  
Keyword(s):  
Risk Factors ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
High Resolution Mass Spectrometry ◽  
Association Studies ◽  
Disease Onset ◽  
Incidence Density ◽  
Exogenous Compounds ◽  
Nested Case Control

Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease and is imposing an increasing social and economic burden in ageing populations. Although the role of environmental factors has been recognised, few established risk factors have been consistently identified. Evidence that exposure to pesticides, herbicides and metals increase PD risk is suggestive, but further research is needed to identify specific compounds that may play a causal role.Large established prospective population studies offer an important opportunity for investigating risk factors in relatively rare diseases such as PD. Within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, 734 incident PD cases have been ascertained, for whom pre-diagnostic blood has been stored. A nested case-control study will be conducted, where one control per case will be selected by incidence density sampling matched by age at recruitment, sex and study centre.Untargeted metabolomics can simultaneously characterize thousands of endogenous and exogenous compounds within a biological sample: the metabolome. Metabolome wide association studies (MWAS) have identified significant differences in the metabolomic profile of older adults with and without PD. We will employ an innovative approach combining liquid and gas phase chromatography with ultra-high-resolution mass spectrometry (LC/GC-UHRMS), to identify exogenous chemical exposures (e.g. pollutants, pesticides and medications), the exposome, in addition to the metabolome.Disease specific variability in blood metabolite compositions may signify the presence of mechanistic aberrations contributing to PD pathogenesis. The combination of metabolome and exposome profiling provides a measure of the continuum from exposure to disease. Allowing previously unavailable richness and depth for characterizing the metabolome and exposome upon which novel discoveries in PD can be made.The EPIC cohort allows us to perform a to study the metabolome and exposome well before disease onset, to eliminate possible effects of levodopa medication or disease-related processes.

scholarly journals Bipolar disorder, a precursor of Parkinson's disease?

2016 ◽  
Vol 10 (4) ◽  
pp. 361-364 ◽  
Author(s):  
Tânia M.S. Novaretti ◽  
Nathália Novaretti ◽  
Vitor Tumas
Keyword(s):  
Parkinson’S Disease ◽  
Bipolar Disorder ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Psychiatric Disorders ◽  
Neurodegenerative Disorder ◽  
Substantia Nigra Pars Compacta ◽  
Dopamine Depletion ◽  
Documented Case ◽  
Dopaminergic Dysfunction

ABSTRACT Parkinson's disease is a neurodegenerative disorder predominantly resulting from dopamine depletion in the substantia nigra pars compacta. Some psychiatric disorders may have dopaminergic dysfunction as their substrate. We describe a well-documented case of Parkinson's disease associated with Bipolar Disorder. Although there is some knowledge about the association between these diseases, little is known about its pathophysiology and correlation. We believe that among various hypotheses, many neurotransmitters are linked to this pathophysiology.

scholarly journals Valproic Acid Neuroprotection in the 6-OHDA Model of Parkinson’s Disease Is Possibly Related to Its Anti-Inflammatory and HDAC Inhibitory Properties

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
José Christian Machado Ximenes ◽  
Kelly Rose Tavares Neves ◽  
Luzia Kalyne A. M. Leal ◽  
Marta Regina Santos do Carmo ◽  
Gerly Anne de Castro Brito ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Valproic Acid ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Wide Spectrum ◽  
Temporal Cortex ◽  
Field Tests ◽  
Tnf Alpha ◽  
Potential Candidate ◽  
Anti Inflammatory

Parkinson’s disease is a neurodegenerative disorder where the main hallmark is the dopaminergic neuronal loss. Besides motor symptoms, PD also causes cognitive decline. Although current therapies focus on the restoration of dopamine levels in the striatum, prevention or disease-modifying therapies are urgently needed. Valproic acid (VA) is a wide spectrum antiepileptic drug, exerting many biochemical and physiological effects. It has been shown to inhibit histone deacetylase which seems to be associated with the drug neuroprotective action. The objectives were to study the neuroprotective properties of VA in a model of Parkinson’s disease, consisting in the unilateral striatal injection of the neurotoxin 6-OHDA. For that, male Wistar rats (250 g) were divided into the groups: sham-operated (SO), untreated 6-OHDA-lesioned, and 6-OHDA-lesioned treated with VA (25 or 50 mg/kg). Oral treatments started 24 h after the stereotaxic surgery and continued daily for 2 weeks, when the animals were subjected to behavioral evaluations (apomorphine-induced rotations and open-field tests). Then, they were sacrificed and had their mesencephalon, striatum, and hippocampus dissected for neurochemical (DA and DOPAC determinations), histological (Fluoro-Jade staining), and immunohistochemistry evaluations (TH, OX-42, GFAP, TNF-alpha, and HDAC). The results showed that VA partly reversed behavioral and neurochemical alterations observed in the untreated 6-OHDA-lesioned rats. Besides, VA also decreased neuron degeneration in the striatum and reversed the TH depletion observed in the mesencephalon of the untreated 6-OHDA groups. This neurotoxin increased the OX-42 and GFAP immunoreactivities in the mesencephalon, indicating increased microglia and astrocyte reactivities, respectively, which were reversed by VA. In addition, the immunostainings for TNF-alpha and HDAC demonstrated in the untreated 6-OHDA-lesioned rats were also decreased after VA treatments. These results were observed not only in the CA1 and CA3 subfields of the hippocampus, but also in the temporal cortex. In conclusion, we showed that VA partly reversed the behavioral, neurochemical, histological, and immunohistochemical alterations observed in the untreated 6-OHDA-lesioned animals. These effects are probably related to the drug anti-inflammatory activity and strongly suggest that VA is a potential candidate to be included in translational studies for the treatment of neurodegenerative diseases as PD.

Sign in / Sign up

Export Citation Format

Share Document