Submitted to: Nutritional Neuroscience
Publication Type: Peer reviewed journal
Publication Acceptance Date: 3/26/2008
Publication Date: 8/11/2008
Citation: Shukitt Hale, B., Lau, F.C., Carey, A.N., Galli, R.L., Spangler, E.L., Ingram, D.K., Joseph, J.A. 2008. Blueberry polyphenols attenuate kainic acid-induced decrements in cognition and alter inflammatory gene expression in rat hippocampus. Nutritional Neuroscience. 11(4):172-182. Interpretive Summary: Cognitive impairment in age-related degenerative diseases such as Alzheimer's disease may be partly due to long-term exposure and incrased susceptibility to inflammation. In the current study, we investigated whether the deleterious effects of inflammation induced by administration of kainic acid, a toxin to the brain, into the brain can be reduced by the polyphenols in blueberries altering the genes associated with inflammation. To this end, 4-month old male rats were fed a diet containing either blueberry, piroxicam (an anti-inflammatory drug)or a control diet containing neither blueberry nor piroxicam for 8 weeks before either Ringers (a solution with chemicals in the same proportion as in animal tissue) or kainic acid, was infused into the brain. Two weeks later, following behavioral testing, the rats were euthanized and RNA was extracted to analyze inflammation-related genes. Kainic acid had deleterious effects on cognitive behaviour as kainic acid injected rats on the control diet performed worse on a behavioral test compared to Ringers injected rats. The blueberry diet, and to a lesser degree, the piroxicam diet, was able to improve cognitive performance. Kainic acid increased the activation of several genes associated with inflammation. Blueberry and piroxicam supplementations were found to attenuate the kainic acid induced increase of some inflammation genes. These results indicated that blueberry polyphenols attenuate learning impairments following a brain toxin and exert anti-inflammatory actions, perhaps by the alteration of genes.
Technical Abstract: Cognitive impairment in age-related neurodegenerative diseases such as Alzheimer's disease may be partly due to long-term exposure and increased susceptibility to inflammatory insults. In the current study we investigated whether polyphenols in blueberries (BBs) can reduce the deleterious effects of inflammation induced by central administration of kainic acid (KA) by altering the expression of genes associated with inflammation. To this end, 4 month old Fischer-344 (F344) rats were fed a control, 0.015% piroxicam (PX, an NSAID) or 2% BB diet for 8 weeks before either Ringers(R)or KA was bilaterally microinfused into the hippocampus. Two weeks later, following behavioral evaluation, the rats were euthanized and total RNA from the hippocampus was extracted and used in real-time quantitative RT-PCR (qRT-PCR) to analyze the expression of inflammation-related genes. KA had deleterious effects on cognitive behavior as KA-injected rats on the control diet exhibited increased latencies to find a hidden platform in the Morris water maze (MWM) compared to R-injected rats and utilized non-spatial strategies during probe trials. The BB diet, and to a lesser degree the PX diet, was able to improve cognitive performance. Immunohistochemical analyses of OX-6 expression revealed that KA produced an inflammatory response by increasing the OX-6 positive areas in the hippocampus of KA-injected rats. KA up-regulated the expression of inflammtory cytokines IL-1beta and TNF-alpa, the neurotrophic factor IGF-1 and the transcription factor NF-kB. BB and PX supplementations were found to attenuate the KA-induced increase in the expression of IL-1beta, TNF-alpha and NF-kB, while only BB was able to augment the increased IGF-1 expression. These results indicate that BB polyphenols attenuate learning impairments following neurotxic insult and exert anti-inflammatory actions perhaps via alteration of gene expression.