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64th Annual Meeting of the German Society of Neurosurgery (DGNC)

German Society of Neurosurgery (DGNC)

26 - 29 May 2013, Düsseldorf

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Neuronal firing activity and gene expression changes in the subthalamic nucleus after transplantation of dopamine neurons in hemiparkinsonian rats

Meeting Abstract

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  • Regina Rumpel - Institute of Neuroanatomy, Hannover Medical School, Hannover, Germany
  • Mesbah Alam - Clinic of Neurosurgery, Hannover Medical School, Hannover, Germany
  • Alexander Klein - Institute of Neuroanatomy, Hannover Medical School, Hannover, Germany
  • Meltem Oezer - Institute of Neuroanatomy, Hannover Medical School, Hannover, Germany
  • Meike Wesemann - Institute of Neuroanatomy, Hannover Medical School, Hannover, Germany
  • Joachim K. Krauss - Clinic of Neurosurgery, Hannover Medical School, Hannover, Germany
  • Kerstin Schwabe - Clinic of Neurosurgery, Hannover Medical School, Hannover, Germany
  • Andreas Ratzka - Institute of Neuroanatomy, Hannover Medical School, Hannover, Germany
  • Claudia Grothe - Institute of Neuroanatomy, Hannover Medical School, Hannover, Germany

Deutsche Gesellschaft für Neurochirurgie. 64. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC). Düsseldorf, 26.-29.05.2013. Düsseldorf: German Medical Science GMS Publishing House; 2013. DocMI.04.10

doi: 10.3205/13dgnc310, urn:nbn:de:0183-13dgnc3106

Published: May 21, 2013

© 2013 Rumpel et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Objective: The loss of dopaminergic (DA) neurons in the substantia nigra pars compacta and the resulting DA depletion in the striatum lead to dysfunction of basal ganglia activity with neuronal hyperactivity in the subthalamic nucleus (STN). In Parkinson's disease (PD) patients and in 6-hydroxy dopamine (6-OHDA) lesioned rats the STN firing rate is enhanced, as well as oscillations in the β-frequency band (15–30 Hz). Intrastriatal transplantation of DA neurons has been shown to re-innervate the host brain and restore DA input.

Method: To better understand the effect of striatal transplantation of DA cells on the STN, we combined behavioral and histological findings with electrophysiological extracellular recordings, as well as qRT-PCR analyses of GABAergic and glutamatergic transporter and receptor genes.

Results: In animals, which were transplanted with cells derived from the mesencephalon of E12 rat embryos in the striatum, the rotational behavior induced by amphetamine was alleviated; further, STN neuronal firing abnormalities were improved. Interestingly, both behavioral and electrophysiological measures were dependent on the number of surviving tyrosine hydroxylase positive cells. In animals with small grafts (300–1000 cells) the recovery of drug-induced rotational behavior was 50%, while rats with large grafts (2000–6000 cells) displayed overcompensation of 116%. Only in rats with large grafts the enhanced firing rate and the coherence of β-oscillatory activity between cortex and STN decreased to the level of naive animals. Although grafted rats displayed restored expression of the GABA synthesizing enzyme Gad67 in the striatum compared to naive rats, the grafts induced a decrease in NMDA receptor subunit expression. Interestingly, the NMDA receptor subunit 2B was also less expressed in the STN, both compared to 6-OHDA-lesioned and naive rats.

Conclusions: In summary, DA grafts partially restore functional deficits and neuronal activity of STN in PD rats. However, functional recovery may be compromised by changes in receptor gene expression induced by DA grafts.