Cells (Oct 2023)

Brain Noradrenergic Innervation Supports the Development of Parkinson’s Tremor: A Study in a Reserpinized Rat Model

  • Nicoló Gabriele Pozzi,
  • Francesco Bolzoni,
  • Gabriele Eliseo Mario Biella,
  • Gianni Pezzoli,
  • Chi Wang Ip,
  • Jens Volkmann,
  • Paolo Cavallari,
  • Esther Asan,
  • Ioannis Ugo Isaias

DOI
https://doi.org/10.3390/cells12212529
Journal volume & issue
Vol. 12, no. 21
p. 2529

Abstract

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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/um2, p p 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.

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