TY  - JOUR
A1  - Pozzi, Nicoló Gabriele
A1  - Bolzoni, Francesco
A1  - Biella, Gabriele Eliseo Mario
A1  - Pezzoli, Gianni
A1  - Ip, Chi Wang
A1  - Volkmann, Jens
A1  - Cavallari, Paolo
A1  - Asan, Esther
A1  - Isaias, Ioannis Ugo
T1  - Brain noradrenergic innervation supports the development of Parkinson’s tremor: a study in a reserpinized rat model
T2  - Cells
N2  - The pathophysiology of tremor in Parkinson’s disease (PD) is evolving towards a complex alteration to monoaminergic innervation, and increasing evidence suggests a key role of the locus coeruleus noradrenergic system (LC-NA). However, the difficulties in imaging LC-NA in patients challenge its direct investigation. To this end, we studied the development of tremor in a reserpinized rat model of PD, with or without a selective lesioning of LC-NA innervation with the neurotoxin DSP-4. Eight male rats (Sprague Dawley) received DSP-4 (50 mg/kg) two weeks prior to reserpine injection (10 mg/kg) (DR-group), while seven male animals received only reserpine treatment (R-group). Tremor, rigidity, hypokinesia, postural flexion and postural immobility were scored before and after 20, 40, 60, 80, 120 and 180 min of reserpine injection. Tremor was assessed visually and with accelerometers. The injection of DSP-4 induced a severe reduction in LC-NA terminal axons (DR-group: 0.024 ± 0.01 vs. R-group: 0.27 ± 0.04 axons/um\(^2\), p < 0.001) and was associated with significantly less tremor, as compared to the R-group (peak tremor score, DR-group: 0.5 ± 0.8 vs. R-group: 1.6 ± 0.5; p < 0.01). Kinematic measurement confirmed the clinical data (tremor consistency (% of tremor during 180 s recording), DR-group: 37.9 ± 35.8 vs. R-group: 69.3 ± 29.6; p < 0.05). Akinetic–rigid symptoms did not differ between the DR- and R-groups. Our results provide preliminary causal evidence for a critical role of LC-NA innervation in the development of PD tremor and foster the development of targeted therapies for PD patients.
KW  - Parkinson’s disease
KW  - tremor
KW  - locus coeruleus
KW  - noradrenaline
KW  - reserpinized rat model
Y1  - 2023
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/35772
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-357721
SN  - 2073-4409
VL  - 12
IS  - 21
ER  -