MPTP-Induced Impairment of Cardiovascular Function.

Publication date: Mar 20, 2020

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the accumulation of Lewy bodies and loss of dopaminergic neurons in the substantia nigra pars compacta (SNpC). MPTP is widely used to generate murine PD model. In addition to classical motor disorders, PD patients usually have non-motor symptoms related to autonomic impairment, which precedes decades before the motor dysfunction. This study’s objective is to examine the effects of MPTP on noradrenergic neurons in the hindbrain, thereby on the cardiovascular function in mice. Adult mice received 10 mg/kg/day of MPTP (4 consecutive days) to generate PD model. Systolic blood pressure was measured by tail cuff system in conscious mice, and baroreflex sensitivity was evaluated by heart rate alteration in response to a transient increase or decrease in blood pressure induced by intravenous infusion of phenylalanine (PE) or sodium nitroprusside (SNP) in anesthetized condition, respectively. Baseline heart rate and heart rate variability were analyzed in both sham and MPTP-treated mice. Dopamine, norepinephrine, and related metabolites in the plasma and brain tissues including SNpC, locus coeruleus (LC), rostroventrolateral medulla (RVLM), and nucleus tractus solitarii (NTS) were measured by liquid chromatography-mass spectrometry (LC-MS). Tyrosine hydroxylase-positive (TH) neurons in above nuclei were quantified by immunoreactivities. We found that in addition to the loss of TH neurons in SNpC, MPTP treatment induced a dramatic reduction of TH cell counts in the LC, RVLM, and NTS. These are associated with significant decreases of dopamine, norepinephrine, and epinephrine in above nuclei. Meanwhile, MPTP induced a lasting effect of baroreflex desensitization, tachycardia, and decreased heart rate variability compared to the sham mice. Notably, MPTP treatment elevated sympathetic outflow and suppressed parasympathetic tonicity according to the heart rate power spectrum analysis. Our results indicate that the loss of TH neurons in the brainstem by MPTP treatment led to impaired autonomic cardiovascular function. These results suggest that MPTP treatment can be used to study the autonomic dysfunction in murine model.

Liu, X., Wei, B., Bi, Q., Sun, Q., Li, L., He, J., Weng, Y., Zhang, S., Mao, G., Bao, Y., Wan, S., Shen, X.Z., Yan, J., and Shi, P. MPTP-Induced Impairment of Cardiovascular Function. 24432. 2020 Neurotox Res.

Concepts Keywords
Autonomic MS
Autonomic Dysfunction Dysfunction
Baroreflex PD neurodegenerative disorder
Blood Pressure Decades motor dysfunction
Brain Baroreflex desensitization tachycardia
Brainstem Motor disorders
Cardiovascular Intravenous infusion
Desensitization Branches of biology
Dopamine Brain
Dopaminergic Neuroscience
Epinephrine Cardiovascular physiology
Heart Rate Reflexes
Heart Rate Variability Catecholamines
Hindbrain Basal ganglia
Immunoreactivities Midbrain
Intravenous Infusion Baroreflex
Lewy Bodies MPTP
Locus Coeruleus Substantia nigra
Mass Spectrometry Norepinephrine
Medulla SNP
Mice
MPTP
Murine
Neurodegenerative Disorder
Neurons
Noradrenergic
Norepinephrine
Nuclei
Nucleus Tractus Solitarii
Outflow
Parasympathetic
Parkinson
Phenylalanine
Plasma
SNP
Sodium Nitroprusside
Spectrum Analysis
Tachycardia
Tonicity
Tyrosine Hydroxylase

Semantics

Type Source Name
disease MESH neurodegenerative disorder
disease MESH motor disorders
drug DRUGBANK L-Phenylalanine
drug DRUGBANK Dopamine
drug DRUGBANK Norepinephrine
drug DRUGBANK L-Tyrosine
drug DRUGBANK Epinephrine
disease MESH tachycardia

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