Amelioration of Motor Performance and Nigrostriatal Dopamine Cell Volume Using a Novel Far-Infrared Ceramic Blanket in an A53T Alpha-Synuclein Transgenic Parkinson’s Disease Mouse Model DOI Creative Commons
Frederick Robert Carrick, Luis Sebástian Alexis Valerio, Kimio Sugaya

et al.

Current Issues in Molecular Biology, Journal Year: 2023, Volume and Issue: 45(12), P. 9823 - 9837

Published: Dec. 6, 2023

We had attended a Parkinson’s Disease (PD) patient for non-healing wound who reported marked decrease in his hand tremor and freezing of gait when was exposed to ceramic far-field infrared (cFIR) blanket. PD is the most frequent motor disorder second neurodegenerative disease after Alzheimer’s (AD). The tremor, rigidity, slowness movement associated with affect up 10 million people throughout world, major contributing factor pathogenesis accumulation propagation pathological α-synuclein (α-Syn) death dopaminergic cells Nigrostriatal system. Efforts slow or stop its spreading have resulted development use drug replacement therapy. Unfortunately, there loss about 70–80% substantia nigral neurons patients by time they are diagnosed PD, various drugs provide only temporary relief their symptoms. There limitations treating many conventional medications, necessitating combination pharmaceutical non-pharmacological therapy as an essential adjunct better address health welfare patients. used male adult A53T alpha-synuclein transgenic mice far-infrared Motor activity assessed using rotarod apparatus, mouse brains were examined quantify fluorescence intensities immunostained samples. significantly shorter stay on rotating bar than wild-type (B6C3H). performance improved cFIR well B6C3H healthy wild cFIR. significant statistical substantive increase cellular composition Striatum nigra cFIR-treated mice. Improvement seen increases cell volume striatum treatment.

Language: Английский

Parkinson’s Disease: Cells Succumbing to Lifelong Dopamine-Related Oxidative Stress and Other Bioenergetic Challenges DOI Open Access
Hirohisa Watanabe, Johannes M. Dijkstra, Toshiharu Nagatsu

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2009 - 2009

Published: Feb. 7, 2024

The core pathological event in Parkinson’s disease (PD) is the specific dying of dopamine (DA) neurons substantia nigra pars compacta (SNc). reasons why SNc DA are especially vulnerable and idiopathic PD has only been found humans still puzzling. two main underlying factors neuron vulnerability appear related to high production, namely (i) toxic effects cytoplasmic metabolism (ii) continuous cytosolic Ca2+ oscillations absence Ca2+-buffer protein calbindin. Both cause oxidative stress by producing highly reactive quinones increasing intra-mitochondrial concentrations, respectively. High expression human cell bodies suggested abundant presence DA-derived pigment neuromelanin, which not such abundance other species associated with toxicity at higher levels. created their production system, despite fact that SN does use unusually amounts energy, explains sensitive various genetic environmental create mitochondrial damage thereby promote PD. Aging increases multiple risk for PD, and, a large extent, accelerated aging. To prevent neurodegeneration, possible approaches discussed here (1) reducing accumulation, (2) blocking oscillations, (3) providing bioenergetic support.

Language: Английский

Citations

9
Unraveling the Interplay of Dopamine, Carbon Monoxide, and Heme Oxygenase in Neuromodulation and Cognition DOI Creative Commons
Nicola Bauer, Dongning Liu,

TanPhat Nguyen

et al.

ACS Chemical Neuroscience, Journal Year: 2024, Volume and Issue: 15(3), P. 400 - 407

Published: Jan. 12, 2024

The dopaminergic system plays important roles in neuromodulation, including prominent complex neurological functions such as cognition, reward, motivation, and memory. Understandably, the highly nature of physiological means that their regulation is intertwined with other signaling pathways, has been demonstrated by numerous studies. Contrary to its public perception being poisonous at all concentrations, carbon monoxide (CO) produced endogenously from heme degradation oxygenase (HO) part process red blood cell turnover. Physiological concentrations CO can reach high micromolar ranges hemoglobin bound form. Low-dose shown therapeutic effects animal models, traumatic brain injury via engaging various hemoprotein targets. As such, HO–CO axis offer beneficial organ protection, anti-inflammation, neuroprotection, among many others. Further, a large number publications have interactions CO, HO, system. In this review, we critically examine experimental evidence holistic fashion context possible dopamine–HO–CO axis. We hope Perspective will stimulate additional investigations into molecular connectivity related open doors development novel therapeutics impact

Language: Английский

Citations

6
Moving to a non-dopaminergic approach for the treatment of OFF fluctuations in Parkinson’s disease DOI Creative Commons
Stuart Isaacson,

Peter Jenner

Clinical Parkinsonism & Related Disorders, Journal Year: 2025, Volume and Issue: unknown, P. 100303 - 100303

Published: Jan. 1, 2025

Language: Английский

Citations

0
Levodopa treatment: impacts and mechanisms throughout Parkinson’s disease progression DOI Creative Commons
Peter Riederer,

Sabrina Strobel,

Toshiharu Nagatsu

et al.

Journal of Neural Transmission, Journal Year: 2025, Volume and Issue: unknown

Published: April 11, 2025

Abstract Treatment with levodopa, a precursor of dopamine (DA), to compensate for the loss endogenous DA in Parkinson’s disease (PD), has been success story over 50 years. However, late stages PD, progressive degeneration dopaminergic neurons and ongoing reduction concentrations make it increasingly difficult maintain normal-like function. Typically, higher doses levodopa are required, fluctuations striatal concentrations—reflecting timing pattern administrations—become more pronounced. These can include highs that induce involuntary movements (levodopa-induced dyskinesia, LID) or lows result insufficient suppression PD symptoms (“OFF” phases). The enhanced primarily arise from buffering capacity, resulting neurons, an increased reliance on levodopa-derived release as “false neurotransmitter” by serotonergic neurons. In many patients, LID OFF-phases be alleviated modifying therapy provide continuous delivery using additional medications, such monoamine oxidase-B (MAO-B) inhibitors, amantadine, receptor agonists. Understanding challenges faced also requires considering striatum is characterized not only but neuroplastic adaptations PD-induced degenerations other neural populations. This review provides broad overview use treating focus underlying science encountered disease.

Language: Английский

Citations

0
A journey through cannabidiol in Parkinson’s disease DOI
Elaine Aparecida Del Bel,

Nubia Barros-Pereira,

Rafaela Ponciano de Moraes

et al.

International review of neurobiology, Journal Year: 2024, Volume and Issue: unknown, P. 65 - 93

Published: Jan. 1, 2024

Language: Английский

Citations

3
Chemogenetic Control of Striatal Astrocytes Improves Parkinsonian Motor Deficits in Mice DOI Creative Commons

Wesley R. Evans,

Sindhuja S. Baskar,

Angelica Vellore

et al.

Glia, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

ABSTRACT Parkinson's disease (PD) is characterized by the degeneration of dopaminergic nigrostriatal inputs, which causes striatal network dysfunction and leads to pronounced motor deficits. Recent evidence highlights astrocytes as a potential local source for neuromodulation. There substantial norepinephrine‐mediated recruitment cortical astrocyte activity during movement locomotion. However, it unclear how in striatum, region devoid norepinephrine neuromodulatory respond Moreover, remains unknown dopamine loss affects whether regulates behavioral deficits PD. We addressed these questions performing astrocyte‐specific calcium recordings manipulations using vivo fiber photometry chemogenetics. find that locomotion elicits over slower timescale than neurons. Acute pharmacological blockade receptors only moderately reduced locomotion‐related activity. Yet, unilateral depletion significantly attenuated responses. Chemogenetic stimulation G i ‐coupled partially improved this functional deficit dopamine‐lesioned mice. In parallel, chemogenetic manipulation restored asymmetrical open‐field exploratory behavior. Together, our results establish novel role signaling modulating function PD highlight non‐neuronal targets therapeutics.

Language: Английский

Citations

0
Longitudinal Dynamics of Clinical and Neurophysiological Changes in Parkinson's Disease: A 4.5-Year Cohort Study DOI

Estefanía Santana‐Román,

Isaac Pérez-Segura, Oscar Arias‐Carrión

et al.

Published: May 7, 2025

Abstract Parkinson's disease (PD) is characterized by progressive motor and non-motor symptoms, yet the longitudinal interplay between clinical progression neurophysiological alterations remains underexplored. In this four-and-a-half-year study, we assessed 22 individuals with PD using Movement Disorder Society–Unified Disease Rating Scale (MDS-UPDRS) transcranial magnetic stimulation (TMS) to evaluate cortical excitability. We analyzed changes in resting threshold (rMT) silent period (CSP) across stages examined impact of COVID-19 pandemic on progression. observed significant function excitability deterioration over time, CSP exhibiting potential as a biomarker These were more pronounced advanced during post-pandemic period, underscoring susceptibility patients environmental stressors. No sex-related differences found or measures. Our findings highlight TMS monitoring suggest that integrating assessments into routine practice may enhance patient management. Longitudinal biomarkers could provide insights trajectory inform therapeutic interventions.

Language: Английский

Citations

0
Early synaptic dysfunction of striatal parvalbumin interneurons in a mouse model of Parkinson’s disease DOI Creative Commons

Quansheng He,

Xiaowen Zhang, Hongyu Yang

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(11), P. 111253 - 111253

Published: Oct. 24, 2024

Language: Английский

Citations

0
Functional activation of dorsal striatum astrocytes improves movement deficits in hemi-parkinsonian mice DOI Creative Commons

Wesley R. Evans,

Sindhuja S. Baskar,

Castro E Costa Ana Raquel

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 2, 2024

Summary Parkinson’s disease (PD) is characterized by the degeneration of dopaminergic nigrostriatal inputs, which causes striatal network dysfunction and leads to pronounced motor deficits. Recent evidence highlights astrocytes as a potential local source modulation. However, it remains unknown how dopamine loss affects astrocyte activity whether regulates behavioral deficits in PD. We addressed these questions performing astrocyte-specific calcium recordings manipulations using vivo fiber photometry chemogenetics. find that locomotion elicits over slower timescale than neurons. Unilateral depletion reduced locomotion-related responses. Chemogenetic activation facilitated activity, improved asymmetrical open field exploratory behavior lesioned mice. Together, our results establish novel role for functional signaling modulating function PD highlight non-neuronal targets therapeutics.

Language: Английский

Citations

0
Dopaminergic Dependency of Cholinergic Pallidal Neurons DOI

Janintzitzic López-Niño,

Montserrat Padilla‐Orozco,

Aidán Ortega

et al.

Neuroscience, Journal Year: 2023, Volume and Issue: 528, P. 12 - 25

Published: Aug. 1, 2023

Language: Английский

Citations

0