Topology of intrastriatal dopaminergic grafts determines functional and emotional outcome in neurotoxin-lesioned rats.
Many Parkinson's disease (PD) patients suffer from anxiety disorders, which often precede the onset of classical motor symptoms. So far, there is no evidence from randomized, placebo-controlled trials for successful treatment of anxiety in patients with PD. Grafts of fetal nigral neurons are currently explored as a restorative cell therapy for PD. In PD animal models, intrastriatal transplantations of embryonic dopaminergic neurons have been shown to ameliorate behavioral defects. In our previous study we showed that expanded and differentiated neural progenitors improved drug-induced rotation behavior and posture balance as a more complex motor task. However, it is not clear whether grafting of these cells affected spontaneous locomotor activity and anxiety-like behavior in 6-OHDA lesioned rats. Therefore, we analyzed behavior of control, lesioned, sham-transplanted, and transplanted rats using open field (OF) and elevated plus maze (EPM). After unilateral 6-OHDA lesion of the medial forebrain bundle, we observed reduced locomotor activity in the EPM (wall-rearing, entries in closed arms) in lesioned and sham-transplanted rats, which correlated with the loss of dopaminergic neurons and apomorphine-induced rotation behavior. Furthermore, anxiety-like behavior in the EPM (entries and time in open arms) was increased in lesioned and sham-transplanted rats. Although exogenous cell replacement improved apomorphine-induced rotation behavior, locomotor activity and anxiety-like behavior was not reconstituted in transplanted rats. However, we provided evidence for an interaction of locomotor activity/anxiety-like behavior with graft localization in the host striatum. These results emphasize the crucial role of graft localization for benefit of restorative cell therapy for PD.
Jungnickel
Julia
J
Hannover Medical School, Institute of Neuroanatomy, Hannover, Germany. jungnickel.julia@mh-hannover.de
Kalve
Ieva
I
Reimers
Linda
L
Nobre
André
A
Wesemann
Maike
M
Ratzka
Andreas
A
Halfer
Nina
N
Lindemann
Christoph
C
Schwabe
Kerstin
K
Töllner
Kathrin
K
Gernert
Manuela
M
Grothe
Claudia
C
D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D016380:Brain Tissue Transplantation; D003342:Corpus Striatum / Q000196:embryology / Q000378:metabolism / Q000637:transplantation*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D016332:Fetal Tissue Transplantation; D007150:Immunohistochemistry; D008474:Medial Forebrain Bundle / Q000503:physiopathology*; D009043:Motor Activity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000637:transplantation*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000196:embryology / Q000378:metabolism / Q000637:transplantation*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine