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
JF  - 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
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357721
SN  - 2073-4409
VL  - 12
IS  - 21
ER  - 
TY  - JOUR
A1  - Isaias, Ioannis U.
A1  - Marzegan, Alberto
A1  - Pezzoli, Gianni
A1  - Marotta, Giorgio
A1  - Canesi, Margherita
A1  - Biella, Gabriele E. M.
A1  - Volkmann, Jens
A1  - Cavallari, Paolo
T1  - A role for locus coeruleus in Parkinson tremor
JF  - Frontiers in Human Neuroscience
N2  - We analyzed rest tremor, one of the etiologically most elusive hallmarks of Parkinson disease(PD), in 12 consecutive PD patients during a specific task activating the locus coeruleus (LC) to investigate a putative role of noradrenaline (NA) in tremor generation and suppression. Clinical diagnosis was confirmed in all subjects by reduced dopamine reuptake transporter (DAT) binding values investigated by single photon computed tomography imaging (SPECT) with [\(^{123}\)I] N-\(\omega\)-fluoropropyl-2 \(\beta\)-carbomethoxy-3 \(\beta\)-(4-iodophenyl) tropane (FP-CIT). The intensity of tremor (i.e., the power of Electromyography [EMG] signals), but not its frequency, significantly increased during the task. In six subjects, tremor appeared selectively during the task. In a second part of the study, we retrospectively reviewed SPECT with FP-CIT data and confirmed the lack of correlation between dopaminergic loss and tremor by comparing DAT binding values of 82 PD subjects with bilateral tremor (n = 27), unilateral tremor (n = 22), and no tremor (n = 33). This study suggests a role of the LC in Parkinson tremor.
KW  - locus coeruleus
KW  - disease
KW  - basal ganglia
KW  - resting tremor
KW  - functional neuroanatomy
KW  - dopamine
KW  - norepinephrine
KW  - progression
KW  - binding
KW  - rat
KW  - noradrenalin
KW  - parkinson disease
KW  - tremor
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133955
VL  - 5
IS  - 179
ER  -