Using microdialysis to monitor dopaminergic support of limb-use control following mesencephalic neurosphere transplantation in a rodent model of Parkinson's Disease

• Published in: Behavioural brain research Vol. 471; p. 115121
• Main Authors: Halfhide, Chloé, Cammarano, Tommie L., Anderson, Kevin A., Galik, Stefani M., Rossignol, Julien, Dunbar, Gary L., Sandstrom, Michael I.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05-08-2024
• Subjects: 6-OHDA; Animals; behavioral response; Corpus Striatum - metabolism; Disease Models, Animal; Dopamine - metabolism; Dopaminergic Neurons - metabolism; Dopaminergic Neurons - physiology; Extremities; Male; Mesencephalon - metabolism; Microdialysis; nomifensine; Oxidopamine - pharmacology; Parkinson Disease - metabolism; Parkinson Disease - physiopathology; Parkinson Disease - therapy; Parkinsonian Disorders - metabolism; Parkinsonian Disorders - physiopathology; Rats; Rats, Sprague-Dawley; stem cell therapy; Substantia Nigra - metabolism; transplant integration; PoB; IHC; 6-OHDA; EMSCs; LMER; BSA; DV; MSCs; SHH; HPLC; ML; PBS; DOPAC; BDNF; stem cell therapy; transplant integration; ACSF; FGF-8; nomifensine; EDTA; AP; HVA; PD; TH; microdialysis; behavioral response; HBSS; BFGF; DA
• ISSN: 0166-4328; 1872-7549; 1872-7549
• DOI: 10.1016/j.bbr.2024.115121

Controlled nigrostriatal dopamine release supports effective limb use during locomotion coordination that becomes compromised after this pathway deteriorates in Parkinson’s Disease (PD). How dopamine release relates to active ongoing behavior control remains unknown. Restoring proper release strategy appears important to successful PD treatment with transplanted dopamine-producing stem cells. This is suggested by apparently distinct behavioral support from tonic or phasic release and corresponding requirements of requisite afferent control exhibited by intact nigrostriatal neurons. Our laboratory previously demonstrated that transplanted dopaminergic cells can elicit skilled movement recovery known to depend on phasic dopamine release. However, efforts to measure this movement-related dopamine release yielded seemingly paradoxical, incongruent results. In response, here we explored whether those previous observations derived from rapid reuptake transport into either transplanted cells or residual, lesion-surviving terminals. We confirmed this using minimal reuptake blockade during intrastriatal microdialysis. After unilateral dopamine depletion, rats received transplants and were subjected to our swimming protocol. Among dopamine-depleted and transplanted rats, treatment supported restoration of limb movement symmetry. Interestingly, subsequent reuptake-restricted microdialysis confirmed distinct swimming-induced dopamine increases clearly occurred among these lesioned/transplanted subjects. Thus, phasic firing control appears to contribute to transplant-derived recovery in Parkinsonian animals.
•Nomifensine assists with observing dopamine and its breakdown using microdialysis.•Mesencephalic cells integrate in vivo without differentiation pre transplantation.•Transplant supported behavioral recovery occurs with frequent limb use and exercise.•Data shows raw dopamine increase with swimming control after transplants.•Behavioral recovery occurred over a short timeline post stem cell transplantation.