Category: Parkinson's Disease: Non-Motor Symptoms
Objective: To investigate the contribution of microglia in MPTP-induced loss of adrenergic neurons and impairment of cardiovascular function.
Background: Parkinson’s disease (PD) is a neurodegenerative disease, characterized by losses of dopaminergic and adrenergic neurons. These are associated with the motor and non-motor symptoms in PD patients. The non-motor syndromes, e.g. autonomic dysfunction, precede decades of motor syndrome. Microglia, the resident immune cells, are activated with the progress of PD, particularly in the autonomic nuclei in the brainstem.
Method: Transgenic CD11-DTR (diphtheria toxin receptor) mice were induced PD by i.p. injection of MPTP (10mg/kg, 4 times). Microglia were depleted by intracerebroventricular infusion of diphtheria toxin (DT; 0.5 ng/g BW/day) after MPTP treatment. Seven days post MPTP treatment, blood pressure (BP), heart rate (HR) and heart rate variability (HRV) are analyzed in anesthetized mice. Tyrosine hydroxylase (TH)-positive cells were assessed in substantial nigra pars compacta (SnPC), rostroventrolateral medulla (RVLM) and nucleus tractus solitarii (NTS). Dopamine, norepinephrine and related metabolites in the plasma and brain tissues were measured by liquid chromatography-mass spectrometry (LC-MS).
Results: Transgenic CD11-DTR (diphtheria toxin receptor) mice were induced PD by i.p. injection of MPTP (10mg/kg, 4 times). Microglia were depleted by intracerebroventricular infusion of diphtheria toxin (DT; 0.5 ng/g BW/day) after MPTP treatment. Seven days post MPTP treatment, blood pressure (BP), heart rate (HR) and heart rate variability (HRV) are analyzed in anesthetized mice. Tyrosine hydroxylase (TH)-positive cells were assessed in substantial nigra pars compacta (SnPC), rostroventrolateral medulla (RVLM) and nucleus tractus solitarii (NTS). Dopamine, norepinephrine and related metabolites in the plasma and brain tissues were measured by liquid chromatography-mass spectrometry (LC-MS).
Conclusion: Our results indicate that depletion of activated microglia significantly attenuates MPTP-induced loss of adrenergic neurons and cardiovascular function. These suggest that activated microglia aggravates MPTP-elicited damage, which may provide a therapeutic window for PD progress.
To cite this abstract in AMA style:
X. Liu, B. Wei, Q. Sun, Q. Bi, X. Shen, P. Shi. Activated microglia contribute to MPTP-induced impairment of cardiovascular function [abstract]. Mov Disord. 2020; 35 (suppl 1). https://www.mdsabstracts.org/abstract/activated-microglia-contribute-to-mptp-induced-impairment-of-cardiovascular-function/. Accessed November 22, 2024.« Back to MDS Virtual Congress 2020
MDS Abstracts - https://www.mdsabstracts.org/abstract/activated-microglia-contribute-to-mptp-induced-impairment-of-cardiovascular-function/