Defective mitochondrial DNA homeostasis in the substantia nigra in Parkinson disease

AbstractNeuromelanin (NM) is a dark pigment that mainly exists in neurons of the substantia nigra pars compacta (SNc). In Parkinson disease (PD) patients, NM concentration decreases gradually with degeneration and necrosis of dopamine neurons, suggesting potential use as a PD biomarker. We aimed to evaluate associations between NM concentration in in vivo SN and PD progression and different motor subtypes using NM magnetic resonance imaging (NM-MRI). Fifty-four patients with idiopathic PD were enrolled. Patients were divided into groups by subtypes with different clinical symptoms: tremor dominant (TD) group and postural instability and gait difficulty (PIGD) group. Fifteen healthy age-matched volunteers were enrolled as controls. All subjects underwent clinical assessment and NM-MRI examination. PD patients showed significantly decreased contrast-to-noise ratio (CNR) values in medial and lateral SN (P < 0.05) compared to controls. CNR values in lateral SN region decreased linearly with PD progression (P = 0.001). PIGD patients showed significant decreases in CNR mean values in lateral SN compared to TD patients (P = 0.004). Diagnostic accuracy of using lateral substantia nigra (SN) in TD and PIGD groups was 79% (sensitivity 76.5%, specificity 78.6%). NM concentration in PD patients decreases gradually during disease progression and differs significantly between PD subtypes. NM may be a reliable biomarker for PD severity and subtype identification.

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Utility of manual fractional anisotropy measurements in the management of patients with Parkinson disease: a feasibility study with a 1.5-T magnetic resonance imaging system

Acta Radiologica Open ◽

10.1177/2058460121993477 ◽

2021 ◽

Vol 10 (2) ◽

pp. 205846012199347

Author(s):

Romulo V de Oliveira ◽

João S Pereira

Keyword(s):

Diffusion Tensor Imaging ◽

Substantia Nigra ◽

Parkinson Disease ◽

Fractional Anisotropy ◽

Diffusion Tensor ◽

Neuronal Damage ◽

Magnetic Resonance Imaging System ◽

Healthy Controls ◽

Clinical Variables ◽

Severity Scores

Background Diffusion tensor imaging has emerged as a promising tool for quantitative analysis of neuronal damage in Parkinson disease, with potential value for diagnostic and prognostic evaluation. Purpose The aim of this study was to examine Parkinson disease-associated alterations in specific brain regions revealed by diffusion tensor imaging and how such alterations correlate with clinical variables. Material and Methods Diffusion tensor imaging was performed on 42 Parkinson disease patients and 20 healthy controls with a 1.5-T scanner. Manual fractional anisotropy measurements were performed for the ventral, intermediate, and dorsal portions of the substantia nigra, as well as for the cerebral peduncles, putamen, thalamus, and supplementary motor area. The correlation analysis between these measurements and the clinical variables was performed using χ2 variance and multiple linear regression. Results Compared to healthy controls, Parkinson disease patients had significantly reduced fractional anisotropy values in the substantia nigra ( P < .05). Some fractional anisotropy measurements in the substantia nigra correlated inversely with duration of Parkinson disease and Parkinson disease severity scores. Reduced fractional anisotropy values in the substantia nigra were also correlated inversely with age variable. fractional anisotropy values obtained for the right and left putamen varied significantly between males and females in both groups. Conclusion Manual fractional anisotropy measurements in the substantia nigra were confirmed to be feasible with a 1.5-T scanner. Diffusion tensor imaging data can be used as a reliable biomarker of Parkinson disease that can be used to support diagnosis, prognosis, and progression/treatment monitoring.

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Parkinson disease, substantia nigra vulnerability, and calbindin expression: Enlightening the darkness?

Movement Disorders ◽

10.1002/mds.27618 ◽

2019 ◽

Vol 34 (2) ◽

pp. 161-163 ◽

Cited By ~ 3

Author(s):

Javier Blesa ◽

Miquel Vila

Keyword(s):

Substantia Nigra ◽

Parkinson Disease

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Bursting in Substantia Nigra Pars Reticulata Neurons In Vitro: Possible Relevance for Parkinson Disease

Journal of Neurophysiology ◽

10.1152/jn.00620.2007 ◽

2007 ◽

Vol 98 (4) ◽

pp. 2311-2323 ◽

Cited By ~ 32

Author(s):

Osvaldo Ibáñez-Sandoval ◽

Luis Carrillo-Reid ◽

Elvira Galarraga ◽

Dagoberto Tapia ◽

Ernesto Mendoza ◽

...

Keyword(s):

Substantia Nigra ◽

Parkinson Disease ◽

Temporal Structure ◽

Projection Neurons ◽

Rate Model ◽

Indirect Pathway ◽

Bath Application ◽

Pattern Generators ◽

Oscillatory Model

Projection neurons of the substantia nigra reticulata (SNr) convey basal ganglia (BG) processing to thalamocortical and brain stem circuits responsible for movement. Two models try to explain pathological BG performance during Parkinson disease (PD): the rate model, which posits an overexcitation of SNr neurons due to hyperactivity in the indirect pathway and hypoactivity of the direct pathway, and the oscillatory model, which explains PD as the product of pathological pattern generators disclosed by dopamine reduction. These models are, apparently, incompatible. We tested the predictions of the rate model by increasing the excitatory drive and reducing the inhibition on SNr neurons in vitro. This was done pharmacologically with bath application of glutamate agonist N-methyl-d-aspartate and GABAA receptor blockers, respectively. Both maneuvers induced bursting behavior in SNr neurons. Therefore synaptic changes forecasted by the rate model induce the electrical behavior predicted by the oscillatory model. In addition, we found evidence that CaV3.2 Ca2+ channels are a critical step in generating the bursting firing pattern in SNr neurons. Other ion channels involved are: hyperpolarization-activated cation channels, high-voltage-activated Ca2+ channels, and Ca2+-activated K+ channels. However, although these channels shape the temporal structure of bursting, only CaV3.2 Ca2+ channels are indispensable for the initiation of the bursting pattern.

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Mitochondrial DNA variants as genetic risk factors for Parkinson disease

European Journal of Neurology ◽

10.1111/ene.13020 ◽

2016 ◽

Vol 23 (8) ◽

pp. 1289-1300 ◽

Cited By ~ 17

Author(s):

C. W. Liou ◽

J. H. Chuang ◽

J. B. Chen ◽

M. M. Tiao ◽

P. W. Wang ◽

...

Keyword(s):

Risk Factors ◽

Mitochondrial Dna ◽

Parkinson Disease ◽

Genetic Risk ◽

Genetic Risk Factors ◽

Dna Variants ◽

Mitochondrial Dna Variants

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