Dokumentdetails
ID
doi:10.1186/s40035-022-00289-y...
Autor
Isonaka, Risa Sullivan, Patti Goldstein, David S.Langue
enEditor
BioMed Central
Kategorie
Neurology
Jahr
2022
Auflistungsdatum
08.12.2022
Schlüsselwörter
synuclein tyrosine hydroxylase norepinephrine immunofluorescence parkinson post-mortem intra-neuronal nerves = 0 times th pathophysiological increased deposition control myocardial smg α-syn pdZusammenfassung
Background Parkinson’s disease (PD) is characterized by intra-neuronal deposition of the protein α-synuclein (α-syn) and by deficiencies of the catecholamines dopamine and norepinephrine (NE) in the brain and heart.
Accumulation of α-syn in sympathetic noradrenergic nerves may provide a useful PD biomarker; however, whether α-syn buildup is pathophysiological has been unclear.
If it were, one would expect associations of intra-neuronal α-syn deposition with catecholaminergic denervation and with decreased NE contents in the same samples.
Methods We assayed immunoreactive α-syn and tyrosine hydroxylase (TH, a marker of catecholaminergic innervation) concurrently with catecholamines in coded post-mortem scalp skin, submandibular gland (SMG), and apical left ventricular myocardial tissue samples from 14 patients with autopsy-proven PD and 12 age-matched control subjects who did not have a neurodegenerative disease.
Results The PD group had increased α-syn in sympathetic noradrenergically innervated arrector pili muscles (5.7 times control, P < 0.0001), SMG (35 times control, P = 0.0011), and myocardium (11 times control, P = 0.0011).
Myocardial TH in the PD group was decreased by 65% compared to the control group ( P = 0.0008), whereas the groups did not differ in TH in either arrector pili muscles or SMG.
Similarly, myocardial NE was decreased by 92% in the PD group ( P < 0.0001), but the groups did not differ in NE in either scalp skin or SMG.
Conclusions PD entails increased α-syn in skin, SMG, and myocardial tissues.
In skin and SMG, augmented α-syn deposition in sympathetic nerves does not seem to be pathogenic.
The pathophysiological significance of intra-neuronal α-syn deposition appears to be organ-selective and prominent in the heart.
Isonaka, Risa,Sullivan, Patti,Goldstein, David S., 2022, Pathophysiological significance of increased α-synuclein deposition in sympathetic nerves in Parkinson’s disease: a post-mortem observational study, BioMed Central
Configurable Safety Tuning of Language Models with Synthetic Preference Data
data preference cst dpo configurable language safety
Affective flexibility as a developmental building block of cognitive reappraisal: An fMRI study
cognitive success affective flexibility
