Alpha-synuclein-induced nigrostriatal degeneration and pramipexole treatment disrupt frontostriatal plasticity DOI Creative Commons
Marianne Benoit‐Marand, Sarah Chevalier, Mélina Decourt

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: March 14, 2024

Abstract Parkinson’s disease is characterized by the degeneration of substantia nigra pars compacta (SNc) dopaminergic neurons, leading to motor and cognitive symptoms. Numerous cellular molecular adaptations following neurodegeneration or dopamine replacement therapy (DRT) have been described in networks but little known regarding associative basal ganglia loops. This study investigated contributions nigrostriatal pramipexole (PPX) on neuronal activity orbitofrontal cortex (OFC), frontostriatal plasticity markers synaptic plasticity. Bilateral was induced viral-mediated expression human mutated alpha-synuclein SNc. Juxtacellular recordings were performed anesthetized rats evaluate OFC. Recordings dorsomedial striatum (DMS) spike probability response OFC stimulation measured before after a high frequency (HFS). Post-mortem analysis included stereological assessment nigral neurodegeneration, BDNF TrkB protein levels. Nigrostriatal led altered firing patterns neurons that restored PPX. HFS an increased DMS, while loss had opposite effect. PPX decreased control failed counteract effect neurodegeneration. These alterations associated with levels DMS. demonstrates both contribute alter fronstostriatal transmission, precluding adequate information processing loops as gateway for development non-motor symptoms side-effects DRT.

Language: Английский

Recent advances in nanotechnology for Parkinson’s disease: diagnosis, treatment, and future perspectives DOI Creative Commons
Virendra Kumar Yadav, Seshathiri Dhanasekaran, Nisha Choudhary

et al.

Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 12

Published: Jan. 22, 2025

Parkinson’s disease is a progressive neurodegenerative that destroys substantia nigra dopaminergic neurons, causing tremors, bradykinesia, rigidity, and postural instability. Current treatment approaches primarily focus on symptom management, employing pharmacological, non-pharmacological, surgical methods. However, these treatments often result in fluctuating symptoms, side effects, progression. Here, the authors have reviewed emerging field of nanomedicine as promising path for treatment, emphasizing its potential to overcome limitations traditional therapies. Nanomedicine utilizes nanoparticles targeted drug delivery, leveraging their small size high surface area volume ratio cross blood-brain barrier deliver therapeutic agents directly affected brain regions. Various nanoparticles, including lipid-based, polymeric, metallic, carbon-based, shown treatment. Additionally, nanocarrier systems like liposomes, nanogels, dendrimers, solid lipid offer controlled sustained release agents, enhancing bioavailability reducing effects. This review provides insights into pathophysiology disease, highlighting mechanisms neurodegeneration, role alpha-synuclein, disruption pathways. It further discusses application gene therapy conjunction with interventions.

Language: Английский

Citations

2
Emerging biophysical techniques for probing synaptic transmission in neurodegenerative disorders DOI
Mayur B. Kale, Nitu L. Wankhede, Ashok Kumar Bishoyi

et al.

Neuroscience, Journal Year: 2024, Volume and Issue: 565, P. 63 - 79

Published: Nov. 26, 2024

Language: Английский

Citations

6
Calbindin and Girk2/Aldh1a1 define resilient vs vulnerable dopaminergic neurons in a primate Parkinson’s disease model DOI Creative Commons

Natalia López‐González del Rey,

Nagore Hernández-Pinedo, Maria Christina Carrillo

et al.

npj Parkinson s Disease, Journal Year: 2024, Volume and Issue: 10(1)

Published: Sept. 2, 2024

The differential vulnerability of dopaminergic neurons the substantia nigra pars compacta (SNc) is a critical and unresolved question in Parkinson´s disease. Studies mice show diverse susceptibility subpopulations nigral to various toxic agents. In primate midbrain, molecular phenotypes their are poorly characterized. We performed detailed histological study determine anatomical distribution different within identified midbrain selective control MPTP-treated monkeys. ventral tier SNc (nigrosome), rich Aldh1a1 Girk2 intermingled, whereas calbindin marker that best identifies most resilient located dorsal tegmental area, recapitulating well-defined dorsoventral axis degeneration neurons. particular, loss Aldh1a1+ was observed parallel progressive development parkinsonism. were main population vulnerable nigrostriatal-projecting neurons, while Aldh1a1- giving rise nigropallidal projections remained relatively preserved. Moreover, bundles entwined dendrites with long trajectories extending towards reticulata emerged from clusters colocalized dense cannabinoid receptor 1 afferent fibers likely representing part striatonigral projection affected human disorders, including conclusion, can be by using Girk2. Further studies needed define afferent/efferent patterns these

Language: Английский

Citations

4
State-dependent modulation of spiny projection neurons controls levodopa-induced dyskinesia in a mouse model of Parkinson's disease DOI Creative Commons
Shenyu Zhai, Qiaoling Cui,

David L. Wokosin

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

In the later stages of Parkinson's disease (PD), patients often manifest levodopa-induced dyskinesia (LID), compromising their quality life. The pathophysiology underlying LID is poorly understood, and treatment options are limited. To move toward filling this gap, intrinsic synaptic changes in striatal spiny projection neurons (SPNs) triggered by sustained elevation dopamine (DA) during were characterized using electrophysiological, pharmacological, molecular behavioral approaches. Our studies revealed that excitability functional corticostriatal connectivity SPNs dyskinetic mice oscillate between on- off-states a cell- state-specific manner. Although levodopa, these rapid oscillations SPN properties depended on both dopaminergic cholinergic signaling. mouse PD model, disrupting M1 muscarinic receptor signaling specifically iSPNs or deleting its downstream partner CalDAG-GEFI blunted oscillation connectivity, enhanced beneficial effects levodopa attenuated severity.

Language: Английский

Citations

0
Neurobiological mechanism of music improving gait disorder in patients with Parkinson’s disease: a mini review DOI Creative Commons
Lingzhi Huang, Qi‐Jun Zhi

Frontiers in Neurology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 3, 2025

Walking ability is essential for human survival and health. Its basic rhythm mainly generated by the central pattern generator of spinal cord. The rhythmic stimulation music to auditory center affects cerebral cortex other higher nerve centers, acts on generator. By means entrainment, can produce walking synchronized with rhythm, control muscle tension, then regulate gait. Basal ganglia dysfunction main cause abnormal gait in patients Parkinson's disease. Music therapy provides external stimulation, recruits neural networks bypass basal synchronizes rhythms both time space through auditory-motor networks, helping promote improvement patterns

Language: Английский

Citations

0
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
Aberrant functional connectome gradient and its neurotransmitter basis in Parkinson's disease DOI Creative Commons
Tao Guo, Cheng Zhou, Jiaqi Wen

et al.

Neurobiology of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 106821 - 106821

Published: Jan. 1, 2025

Language: Английский

Citations

0
Dopamine depletion weakens direct pathway modulation of SNr neurons DOI Creative Commons
Asier Aristieta, John E. Parker, Ya Gao

et al.

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 196, P. 106512 - 106512

Published: April 24, 2024

Neurons in the substantia nigra reticulata (SNr) transmit information about basal ganglia output to dozens of brain regions thalamocortical and brainstem motor networks. Activity SNr neurons is regulated by convergent input from upstream nuclei, including GABAergic inputs striatum external globus pallidus (GPe). convey direct pathway, while GPe indirect pathway. Chronic loss dopamine, as occurs Parkinson's disease, disrupts balance pathway at level striatum, but question how dopamine affects propagation along these pathways outside less well understood. Using a combination vivo slice electrophysiology, we find that depletion selectively weakens pathway's influence over neural activity due changes decay kinetics GABA-mediated synaptic currents. signaling was not affected, resulting an inversion normal inhibitory control through SNr. These results highlight contribution cellular mechanisms impact responses disease.

Language: Английский

Citations

3
Tonic dendritic GABA release by substantia nigra dopaminergic neurons DOI Open Access
DeNard V. Simmons, Oscar Andrés Moreno-Ramos, Divya Raj

et al.

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

Published: March 30, 2024

Abstract Recent studies have demonstrated the importance of extrastriatal dopamine release in emergence network dysfunction underlying motor deficits Parkinson’s disease (PD). To better characterize actions on substantia nigra pars reticulata (SNr) GABAergic neurons, optogenetic and electrophysiological tools were used ex vivo mouse brain slices to monitor synaptic transmission arising from globus pallidus externa (GPe) neurons. As predicted by previous work, activation D2 receptors (D2Rs) suppressed GABA evoked stimulation GPe axons. However, D2R also a tonic, A receptor-mediated inhibition SNr spiking. D2R-mediated tonic led roughly 30% increase spiking rate. Chemogenetic terminals or excitation astrocytes did not affect SNr. In contrast, chemogenetic dopaminergic neurons knocking down expression aldehyde dehydrogenase 1A1 (ALDH1A1) blunted signaling. Antagonizing D1 striatonigral modestly increased Lastly, progressive model PD targeting was lost. Taken together, these observations suggest that are co-released dendrites ALDH1A1-expressing course through The co-release transmitters could serve promote movement making less responsive phasic activity indirect pathway circuitry lowering basal rates.

Language: Английский

Citations

1
Alpha-synuclein-induced nigrostriatal degeneration and pramipexole treatment disrupt frontostriatal plasticity DOI Open Access
Sarah Chevalier, Mélina Decourt, Maureen Francheteau

et al.

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

Published: Feb. 21, 2024

ABSTRACT BACKGROUND Parkinson’s disease is characterized by the degeneration of substantia nigra pars compacta (SN c ) dopaminergic neurons, leading to motor and cognitive symptoms. Numerous cellular molecular adaptations due degenerative process or dopamine replacement therapy (DRT) have been described in networks but little known regarding associative basal ganglia loops. OBJECTIVE To investigate contributions nigrostriatal pramipexole (PPX) on neuronal activity orbitofrontal cortex (OFC), frontostriatal plasticity markers synaptic plasticity. METHODS Bilateral was induced viral-mediated overexpression human mutated alpha-synuclein SNc. Juxtacellular recordings were performed anesthetized rats evaluate OFC. Recordings dorsomedial striatum (DMS) spike probability response OFC stimulation measured before after a high frequency (HFS). Post-mortem analysis included stereological assessment nigral neurodegeneration, BDNF TrkB levels. RESULTS Nigrostriatal neurodegeneration led altered firing patterns neurons that restored PPX. HFS an increased DMS, while loss had opposite effect. PPX decreased following control failed counteract effect neurodegeneration. These alterations associated with levels TrkB. CONCLUSIONS Both concur alter fronstostriatal transmission, precluding adequate information processing loops as gateway for development non-motor symptoms side-effects DRT.

Language: Английский

Citations

0