title: Environmental enrichment affects striatal graft morphology and functional recovery.
abstract: Environmental conditions and behavioural experience can affect neuronal function and morphology. It is less well known whether such factors also influence the growth, integration and functional recovery provided by neural grafts placed within the damaged brain. Here we report on the effects of differential housing conditions on striatal graft morphology and functional recovery after striatal lesions. Rats were pretrained on a skilled bilateral forelimb task, the staircase test, and lesioned unilaterally in the lateral dorsal striatum with quinolinic acid. One group of lesioned animals was given suspension grafts of E15 whole ganglionic eminence implanted into the lesioned striatum. Following transplantation, the animals were housed either in standard cages (four per cage) or in enriched environment housing conditions (10 per cage) with tunnels, ladders and increased living space available for exploration, social interaction and play. The differentially housed animals were retested on the skilled staircase test at two separate time points. Repeated testing, environmental enrichment and transplantation positively influenced behavioural recovery. Partial recovery was observed bilaterally amongst the grafted animals in both housing conditions. Nevertheless, the grafted animals housed in the enriched environment performed significantly better in the final test compared with all of the other experimental groups. The grafts survived equally well under both housing conditions but the grafts of animals housed in the enriched environment contained larger projection neurons and were somewhat better reinnervated by dopaminergic afferents. An increased level of striatal brain-derived neurotrophic factor was observed in the control animals housed under the enriched compared with the standard conditions. The results indicate that an enriched environment can affect both graft function and graft morphology through as yet unknown mechanisms.
authors.affiliation: Brain Repair Group, School of Biosciences, Cardiff University, Museum Avenue Box 911, Cardiff CF10 3US, UK. dobrossymd@cf.ac.uk
authors.forename: Máté D
authors.initials: MD
authors.lastname: Döbrössy
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Dunnett
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000139:chemically induced / Q000628:therapy*; D016380:Brain Tissue Transplantation / Q000379:methods*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002452:Cell Count; D003714:Denervation; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004780:Environment, Controlled; D007839:Functional Laterality / Q000502:physiology; D006085:Graft Survival / Q000502:physiology*; D008297:Male; D017072:Neostriatum / Q000166:cytology / Q000502:physiology* / Q000601:surgery; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000378:metabolism; D009498:Neurotoxins; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D010750:Phosphoproteins