Cellular and Synaptic Dysfunctions in Parkinson’s Disease: Stepping Out of the Striatum

Cells, Journal Year: 2019, Volume and Issue: 8(9), P. 1005 - 1005

Published: Aug. 29, 2019

The basal ganglia (BG) are a collection of interconnected subcortical nuclei that participate in great variety functions, ranging from motor programming and execution to procedural learning, cognition, emotions. This network is also the region primarily affected by degeneration midbrain dopaminergic neurons localized substantia nigra pars compacta (SNc). causes cellular synaptic dysfunctions BG network, which responsible for appearance symptoms Parkinson’s disease. Dopamine (DA) modulation consequences its loss on striatal microcircuit have been extensively studied, because discrete nature DA innervation other nuclei, action outside striatum has considered negligible. However, there growing body evidence supporting functional extrastriatal both excitability transmission. In this review, relevance normal pathological conditions will be discussed.

Language: Английский

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Contribution of the Cerebellum and the Basal Ganglia to Language Production: Speech, Word Fluency, and Sentence Construction—Evidence from Pathology

The Cerebellum, Journal Year: 2020, Volume and Issue: 20(2), P. 282 - 294

Published: Oct. 29, 2020

Abstract Evidence reported in recent decades increasingly confirms that both the cerebellum and basal ganglia, which are primarily involved movement control, also have a significant role vast range of cognitive affective functions. from pathology indicates disorders some aspects language production follow damage or respectively i.e., speech, word fluency, sentence construction, identifiable neuropsychological profiles most manifestations can be specifically attributed to dysfunctions mechanisms supported by one other these structures. The ganglia reciprocally interconnected. Thus, it is plausible observed when involves structures could remote effects abnormal activity other. However, purely clinical-neuropsychological perspective, primary network difficult disentangle. Functional neuroimaging non-invasive brain stimulation techniques likely represent indispensable support for achieving this goal.

Language: Английский

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Parvalbumin⁺and Npas1⁺Pallidal Neurons Have Distinct Circuit Topology and Function

Journal of Neuroscience, Journal Year: 2020, Volume and Issue: 40(41), P. 7855 - 7876

Published: Aug. 31, 2020

The external globus pallidus (GPe) is a critical node within the basal ganglia circuit. Phasic changes in activity of GPe neurons during movement and their alterations Parkinson's disease (PD) argue that important motor control. Parvalbumin-positive (PV + ) Npas1 are two principal neuron classes GPe. distinct electrophysiological properties axonal projection patterns these serve different roles regulating output. However, causal relationship between remains to be established. Here, by using optogenetic approaches mice (both males females), we showed PV promoted suppressed locomotion, respectively. Moreover, under synaptic influences from subthalamic nucleus (STN). Additionally, found selective weakening STN inputs chronic 6-hydroxydopamine lesion model PD. This finding reinforces idea reciprocally connected GPe–STN network plays key role symptomatology thus provides basis for future circuit-based therapies. SIGNIFICANCE STATEMENT pallidum key, yet an understudied component ganglia. Neural goes awry neurologic diseases, such as disease. While this strongly argues control, it has been difficult establish pallidal function/dysfunction. was part because cellular complexity pallidum. types have opposing In addition, described differences influence. Importantly, our research new insights into circuit mechanisms explain hypokinetic features

Language: Английский

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Cortical disinhibition in Parkinson’s disease

Brain, Journal Year: 2020, Volume and Issue: 143(11), P. 3408 - 3421

Published: July 31, 2020

In Parkinson's disease, striatal dopamine depletion produces profound alterations in the neural activity of cortico-basal ganglia motor loop, leading to dysfunctional output and parkinsonism. A key regulator is balance between excitation inhibition primary cortex, which can be assessed humans with transcranial magnetic stimulation techniques. Despite decades research, functional state cortical disease remains uncertain. Towards resolving this issue, we applied paired-pulse protocols 166 patients (57 levodopa-naïve, 50 non-dyskinetic, 59 dyskinetic) 40 healthy controls (age-matched levodopa-naïve group). All were studied OFF medication. analyses performed fully automatic procedures avoid confirmation bias, systematically considered excluded several potential confounding factors such as age, gender, resting threshold, EMG background amplitude evoked elicited by single-pulse test stimuli. Our results show that short-interval intracortical decreased compared controls. This reduction was obtained relatively low-intensity conditioning stimuli (80% threshold) not associated any significant increase facilitation or same stimuli, supporting involvement inhibitory circuits. Short-interval similarly reduced non-dyskinetic dyskinetic patients. Importantly, control subjects also on less affected side (n = 145), even de novo drug-naïve whom minimally symptomatic (lateralized Unified Disease Rating Scale part III 0 1, n 23). These suggest disinhibition a very early, possibly prodromal feature disease.

Language: Английский

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Sphingolipids in neuroinflammation: a potential target for diagnosis and therapy

BMB Reports, Journal Year: 2020, Volume and Issue: 53(1), P. 28 - 34

Published: Jan. 31, 2020

Sphingolipids are ubiquitous building blocks of eukaryotic cell membranes that function as signaling molecules for regulating a diverse range cellular processes, including proliferation, growth, survival, immune-cell trafficking, vascular and epithelial integrity, inflammation. Recently, several studies have highlighted the pivotal role sphingolipids in neuroinflammatory regulation. multiple functions, induction expression various inflammatory mediators regulation neuroinflammation by directly effecting cells central nervous system. Accumulating evidence points to sphingolipid engagement disorders, Alzheimer's Parkinson's diseases. Abnormal alterations, which involves an increase ceramide decrease sphingosine kinase, observed during disease. These trends early disease development, thus highlight potential new therapeutic diagnostic target [BMB Reports 2020; 53(1): 28-34].

Language: Английский

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