Morphological and cellular changes within embryonic striatal grafts associated with enriched environment and involuntary exercise.
Environmental enrichment (EE) and exercise have been implicated in influencing behaviour and altering neuronal processes associated with cellular morphology in both 'normal' and injured states of the CNS. Using a rodent model of Huntington's disease, we investigated whether prolonged EE or involuntary exercise can induce morphological and cellular changes within embryonic striatal transplants. Adult rats were trained on the Staircase test--requiring fine motor control to reach and collect reward pellets--prior to being lesioned unilaterally in the dorsal neostriatum with quinolinic acid. The lesioned animals received E15 whole ganglionic eminence cell suspension grafts followed by housing in EE or standard cages. Half of the animals in standard cages received daily forced exercise on a treadmill. The grafted animals showed significant functional recovery on both the Staircase test and in drug-induced rotation. Neither the housing conditions nor the training had an impact on the behaviour, with the exception of the treadmill reducing the ipsilateral drug-induced rotation observed amongst the lesioned animals. However, the animals housed in the EE had significantly increased striatal brain-derived neurotrophic factor (BDNF) levels, and graft neurons in these animals exhibited both greater spine densities and larger cell volumes. Animals on forced exercise regime had reduced BDNF levels and grafted cells with sparser spines. The study suggests that the context of the animal can affect the plasticity of transplanted cells. Appropriately exploiting the underlying, and yet unknown, mechanisms could lead the way to improved anatomical and potentially functional integration of the graft.
Döbrössy
Máté D
MD
Brain Repair Group, School of Biosciences, Cardiff University, Museum Avenue Box 911, Cardiff CF10 3US, UK. dobrossymd@cf.ac.uk
Dunnett
Stephen B
SB
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D048430:Cell Shape / Q000502:physiology; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology* / Q000196:embryology / Q000637:transplantation*; D049229:Dendritic Spines / Q000502:physiology / Q000648:ultrastructure; D004195:Disease Models, Animal; D004780:Environment, Controlled; D005260:Female; D020233:Gait Disorders, Neurologic / Q000628:therapy; D006085:Graft Survival / Q000502:physiology*; D006816:Huntington Disease / Q000628:therapy*; D009043:Motor Activity / Q000502:physiology; D010805:Physical Conditioning, Animal / Q000502:physiology*; D010812:Physical Stimulation / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D016896:Treatment Outcome; D015854:Up-Regulation / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor