TY  - JOUR
AU  - Statz, Meike
AU  - Weber, Hanna
AU  - Weis, Frederike
AU  - Kober, Maria
AU  - Bathel, Henning
AU  - Plocksties, Franz
AU  - van Rienen, Ursula
AU  - Timmermann, Dirk
AU  - Storch, Alexander
AU  - Fauser, Mareike
TI  - Subthalamic nucleus deep brain stimulation induces functional deficits in norepinephrinergic neurotransmission in a Parkinson’s disease model
JO  - Brain research
VL  - 1841
SN  - 0006-8993
CY  - Amsterdam
PB  - Elsevier
M1  - DZNE-2024-00949
SP  - 149128
PY  - 2024
AB  -  Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a successful treatment option in Parkinson's disease (PD) for different motor and non-motor symptoms, but has been linked to postoperative cognitive impairment.Since both dopaminergic and norepinephrinergic neurotransmissions play important roles in symptom development, we analysed STN-DBS effects on dopamine and norepinephrine availability in different brain regions and morphological alterations of catecholaminergic neurons in the 6-hydroxydopamine PD rat model.We applied one week of continuous unilateral STN-DBS or sham stimulation, respectively, in groups of healthy and 6-hydroxydopamine-lesioned rats to quantify dopamine and norepinephrine contents in the striatum, olfactory bulb and dentate gyrus. In addition, we analysed dopaminergic cell counts in the substantia nigra pars compacta and area tegmentalis ventralis and norepinephrinergic neurons in the locus coeruleus after one and six weeks of STN-DBS.In 6-hydroxydopamine-lesioned animals, one week of STN-DBS did not alter dopamine levels, while striatal norepinephrine levels were decreased. However, neither one nor six weeks of STN-DBS altered dopaminergic neuron numbers in the midbrain or norepinephrinergic neuron counts in the locus coeruleus. Dopaminergic fibre density in the dorsal and ventral striatum also remained unchanged after six weeks of STN-DBS. In healthy animals, one week of STN-DBS resulted in increased dopamine levels in the olfactory bulb and decreased contents in the dentate gyrus, but had no effects on norepinephrine availability.STN-DBS modulates striatal norepinephrinergic neurotransmission in a PD rat model. Additional behavioural studies are required to investigate the functional impact of this finding.
KW  - Animals
KW  - Subthalamic Nucleus: metabolism
KW  - Deep Brain Stimulation: methods
KW  - Male
KW  - Oxidopamine: toxicity
KW  - Synaptic Transmission: physiology
KW  - Dopamine: metabolism
KW  - Disease Models, Animal
KW  - Norepinephrine: metabolism
KW  - Rats
KW  - Parkinson Disease: metabolism
KW  - Parkinson Disease: therapy
KW  - Dopaminergic Neurons: metabolism
KW  - Olfactory Bulb: metabolism
KW  - Rats, Sprague-Dawley
KW  - Corpus Striatum: metabolism
KW  - Dentate Gyrus: metabolism
KW  - Parkinsonian Disorders: metabolism
KW  - Parkinsonian Disorders: therapy
KW  - Parkinsonian Disorders: physiopathology
LB  - PUB:(DE-HGF)16
C6  - pmid:39053685
DO  - DOI:10.1016/j.brainres.2024.149128
UR  - https://pub.dzne.de/record/271077
ER  -