TY - JOUR
T1 - Behavioral and neurochemical responses derived from dopaminergic intrastriatal grafts in hemiparkinsonian rats engaged in a novel motor task
AU - Bhupal, Parnit K.
AU - Anderson, Kevin A.
AU - Shall, Gabrielle P.
AU - Lynn, Jonathan D.
AU - Hoolsema, Katrina S.
AU - Rossignol, Julien
AU - Dunbar, Gary L.
AU - Sandstrom, Michael I.
N1 - Funding Information:
This research was funded by The Field Neurosciences Institute , the John G. Kulhavi Professorship of Neuroscience , and Central Michigan University’s College of Humanities and Social and Behavioral Sciences .
Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/9/1
Y1 - 2018/9/1
N2 - 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.
AB - 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.
KW - Drug-Induced rotation
KW - Limb-Use asymmetry
KW - Mesenchymal stem cells
KW - Parkinson's disease
KW - Stem cell therapy
KW - Unilateral 6-hydroxydopamine rodent model
KW - phasic/tonic dopamine release
UR - http://www.scopus.com/inward/record.url?scp=85049599333&partnerID=8YFLogxK
U2 - 10.1016/j.jneumeth.2018.06.005
DO - 10.1016/j.jneumeth.2018.06.005
M3 - Article
C2 - 29924980
AN - SCOPUS:85049599333
VL - 307
SP - 149
EP - 163
JO - Journal of Neuroscience Methods
JF - Journal of Neuroscience Methods
SN - 0165-0270
ER -