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Subthalamic nucleus but not entopeduncular nucleus deep brain stimulation enhances neurogenesis in the SVZ-olfactory bulb system of Parkinsonian rats.
Fauser, Mareike; Payonk, Jan Philipp; Weber, Hanna; Statz, Meike; Winter, Christine; Hadar, Ravit; Appali, Revathi; van Rienen, Ursula; Brandt, Moritz D; Storch, Alexander.
Affiliation
  • Fauser M; Department of Neurology, University of Rostock, Rostock, Germany.
  • Payonk JP; Institute of General Electrical Engineering, University of Rostock, Rostock, Germany.
  • Weber H; Department of Neurology, University of Rostock, Rostock, Germany.
  • Statz M; Department of Neurology, University of Rostock, Rostock, Germany.
  • Winter C; Department of Psychiatry and Neurosciences, Charité University Medicine Berlin, Berlin, Germany.
  • Hadar R; Department of Psychiatry and Neurosciences, Charité University Medicine Berlin, Berlin, Germany.
  • Appali R; Institute of General Electrical Engineering, University of Rostock, Rostock, Germany.
  • van Rienen U; Department of Ageing of Individuals and Society, University of Rostock, Rostock, Germany.
  • Brandt MD; Institute of General Electrical Engineering, University of Rostock, Rostock, Germany.
  • Storch A; Department of Ageing of Individuals and Society, University of Rostock, Rostock, Germany.
Front Cell Neurosci ; 18: 1396780, 2024.
Article in En | MEDLINE | ID: mdl-38746080
ABSTRACT

Introduction:

Deep brain stimulation (DBS) is a highly effective treatment option in Parkinson's disease. However, the underlying mechanisms of action, particularly effects on neuronal plasticity, remain enigmatic. Adult neurogenesis in the subventricular zone-olfactory bulb (SVZ-OB) axis and in the dentate gyrus (DG) has been linked to various non-motor symptoms in PD, e.g., memory deficits and olfactory dysfunction. Since DBS affects several of these non-motor symptoms, we analyzed the effects of DBS in the subthalamic nucleus (STN) and the entopeduncular nucleus (EPN) on neurogenesis in 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian rats.

Methods:

In our study, we applied five weeks of continuous bilateral STN-DBS or EPN-DBS in 6-OHDA-lesioned rats with stable dopaminergic deficits compared to 6-OHDA-lesioned rats with corresponding sham stimulation. We injected two thymidine analogs to quantify newborn neurons early after DBS onset and three weeks later. Immunohistochemistry identified newborn cells co-labeled with NeuN, TH and GABA within the OB and DG. As a putative mechanism, we simulated the electric field distribution depending on the stimulation site to analyze direct electric effects on neural stem cell proliferation.

Results:

STN-DBS persistently increased the number of newborn dopaminergic and GABAergic neurons in the OB but not in the DG, while EPN-DBS does not impact neurogenesis. These effects do not seem to be mediated via direct electric stimulation of neural stem/progenitor cells within the neurogenic niches.

Discussion:

Our data support target-specific effects of STN-DBS on adult neurogenesis, a putative modulator of non-motor symptoms in Parkinson's disease.
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Front Cell Neurosci Year: 2024 Document type: Article Affiliation country: Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Front Cell Neurosci Year: 2024 Document type: Article Affiliation country: Country of publication: