Parkinson‐like early autonomic dysfunction induced by vagal application of DOPAL in rats

Abstract

Aim To understand why autonomic failures, a common non‐motor symptom of Parkinson's disease (PD), occur earlier than typical motor disorders. Methods Vagal application of DOPAL (3,4‐dihydroxyphenylacetaldehyde) to simulate PD‐like autonomic dysfunction and understand the connection between PD and cardiovascular dysfunction. Molecular and morphological approaches were employed to test the time‐dependent alternation of α‐synuclein aggregation and the ultrastructure changes in the heart and nodose (NG)/nucleus tractus solitarius (NTS). Results Blood pressure (BP) and baroreflex sensitivity of DOPAL‐treated rats were significantly reduced accompanied with a time‐dependent change in orthostatic BP, consistent with altered echocardiography and cardiomyocyte mitochondrial ultrastructure. Notably, time‐dependent and collaborated changes in Mon‐/Tri‐α‐synuclein were paralleled with morphological alternation in the NG and NTS. Conclusion These all demonstrate that early autonomic dysfunction mediated by vagal application of DOPAL highly suggests the plausible etiology of PD initiated from peripheral, rather than central site. It will provide a scientific basis for the prevention and early diagnosis of PD.

The Catecholaldehyde Hypothesis for the Pathogenesis of Catecholaminergic Neurodegeneration: What We Know and What We Do Not Know

“…A recent study involved DOPAL injection into the vagus nerve, to help understand the frequent association of autonomic failure with PD [ 137 ]. DOPAL-treated rats had evidence of baroreflex dysfunction, orthostatic hypotension, and time-dependent associated changes in αS monomers/trimers.…”

Too much for your own good: Excessive dopamine damages neurons and contributes to Parkinson's disease

“…Another notable phenotype of these mice is an increased dopamine concentration in cardiac tissue, which correlates with increased DOPAC and Cys‐dopamine. In this regard, a recent article explored the effect of DOPAL vagal injection in rats (Sun et al., 2021) and its possible association with early autonomic dysfunction, a well‐recognized non‐motor symptom of PD. DOPAL‐injected rats displayed severe changes in blood orthostatic pressure, alterations of myocardium ultrastructure, and accumulation of high‐molecular‐weight aSyn species (Sun et al., 2021).…”

“…In this regard, a recent article explored the effect of DOPAL vagal injection in rats (Sun et al., 2021) and its possible association with early autonomic dysfunction, a well‐recognized non‐motor symptom of PD. DOPAL‐injected rats displayed severe changes in blood orthostatic pressure, alterations of myocardium ultrastructure, and accumulation of high‐molecular‐weight aSyn species (Sun et al., 2021). Thus, the TH‐HI mouse model could be employed to further investigate the interplay among catecholamine dyshomeostasis, orthostatic hypotension, and aSyn aggregation in the periphery, both in PD and other disorders such as pure autonomic failure.…”

Synchronous monitoring of brain‐heart electrophysiology using heart rate variability coupled with rapid quantitative electroencephalography in orthostatic hypotension patients with α‐synucleinopathies: Rapid prediction of orthostatic hypotension and preliminary exploration of brain stimulation therapy

“…Among them, autonomic dysfunction with orthostatic hypotension (OH) as the main manifestation can cause cerebral hypoperfusion and other adverse consequences, 4,5 even affecting survival rates 6 . OH may occur before the onset of orthostatic symptoms and requires treatment 7 . Therefore, it is of great significance to discover non‐invasive identification markers to facilitate early treatment.…”