Behavioral and neurochemical responses derived from dopaminergic intrastriatal grafts in hemiparkinsonian rats engaged in a novel motor task

Parnit K. Bhupal, Kevin A. Anderson, Gabrielle P. Shall, Jonathan D. Lynn, Katrina S. Hoolsema, Julien Rossignol, Gary L. Dunbar, Michael I. Sandstrom

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Putative treatments derived from in vivo stem cell transplant-derived dopamine (DA) in hemiparkinsonian rats have been assessed via DA-agonist-induced rotations involving imbalanced intra-hemispheric striatal DA receptor stimulation. However, such tests obscure the natural responses of grafts to sensory stimuli, and drug-induced plasticity can modify the circuit being tested. Thus, we propose an alternative testing strategy using a novel water tank swimming apparatus. New method: Microdialysis was used to compare striatal DA levels when rats were: (1) in a rest-phase within a bowl-shaped apparatus, or (2) in an active forced-swim phase within a specially-equipped water tank. Resting-phase DA release levels were compared with active-phase levels obtained while rats were required to swim in the water-tank task. Behavioral variables such as asymmetric circling while swimming (rotations), front-limb strokes, and front-limb reaches were captured by a camera for analysis. Results and comparison with existing methods: Transplanted cells had a very modest effect on percentage of contralateral front-limb strokes, but did not reduce lesion-induced rotational asymmetry in the swim task. Neither striatal DA levels, nor their breakdown products, were significantly different between transplanted and sham-transplanted groups. Our new behavioral test eliminates the need for pharmacological stimulation, enabling simultaneous assessment of DA released in resting and active phases to explore graft control. Conclusions: Our new method allows for accurate assessments of stem cell therapy for PD as an alternative to “rotation” tests. Use of natural motivations to engage in sensory-driven motor tasks provides more accurate insights into ongoing graft-derived behavioral support.

Original languageEnglish
Pages (from-to)149-163
Number of pages15
JournalJournal of Neuroscience Methods
Volume307
DOIs
StatePublished - Sep 1 2018

Keywords

  • Drug-Induced rotation
  • Limb-Use asymmetry
  • Mesenchymal stem cells
  • Parkinson's disease
  • Stem cell therapy
  • Unilateral 6-hydroxydopamine rodent model
  • phasic/tonic dopamine release

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