title: Blueberry supplementation attenuates microglial activation in hippocampal intraocular grafts to aged hosts.
abstract: Transplantation of central nervous tissue has been proposed as a therapeutic intervention for age-related neurodegenerative diseases and stroke. However, survival of embryonic neuronal cells is hampered by detrimental factors in the aged host brain such as circulating inflammatory cytokines and oxidative stress. We have previously found that supplementation with 2% blueberry in the diet increases graft growth and neuronal survival in intraocular hippocampal grafts to aged hosts. In the present study we explored possible biochemical mechanisms for this increased survival, and we here report decreased microglial activation and astrogliosis in intraocular hippocampal grafts to middle-aged hosts fed a 2% blueberry diet. Markers for astrocytes and for activated microglial cells were both decreased long-term after grafting to blueberry-treated hosts compared with age-matched rats on a control diet. Similar findings were obtained in the host brain, with a reduction in OX-6 immunoreactive microglial cells in the hippocampus of those recipients treated with blueberry. In addition, immunoreactivity for the pro-inflammatory cytokine IL-6 was found to be significantly attenuated in intraocular grafts by the 2% blueberry diet. These studies demonstrate direct effects of blueberry upon microglial activation both during isolated conditions and in the aged host brain and suggest that this nutraceutical can attenuate age-induced inflammation.
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Willis
authors.forename: Linnea
authors.initials: L
authors.lastname: Freeman
authors.forename: Paula C
authors.initials: PC
authors.lastname: Bickford
authors.forename: E Matthew
authors.initials: EM
authors.lastname: Quintero
authors.forename: Claudia D
authors.initials: CD
authors.lastname: Umphlet
authors.forename: Alfred B
authors.initials: AB
authors.lastname: Moore
authors.forename: Laura
authors.initials: L
authors.lastname: Goetzl
authors.forename: Ann-Charlotte
authors.initials: AC
authors.lastname: Granholm
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D029798:Blueberry Plants / Q000737:chemistry*; D016380:Brain Tissue Transplantation / Q000379:methods; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism; D019587:Dietary Supplements; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006085:Graft Survival / Q000187:drug effects*; D006624:Hippocampus / Q000166:cytology* / Q000637:transplantation*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008840:Microfilament Proteins; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: C112986:AIF1 protein, human; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D000949:Histocompatibility Antigens Class II; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008840:Microfilament Proteins; D010936:Plant Extracts