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Blueberry polyphenols attenuate kainic acid-induced decrements in cognition and alter inflammatory gene expression in rat hippocampus.
Nutr Neurosci. 2008 Aug; 11(4):172-82.NN

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 can reduce the deleterious effects of inflammation induced by central administration of kainic acid by altering the expression of genes associated with inflammation. To this end, 4-month-old male Fischer-344 (F344) rats were fed a control, 0.015% piroxicam (an NSAID) or 2% blueberry diet for 8 weeks before either Ringer's buffer or kainic acid was bilaterally micro-infused into the hippocampus. Two weeks later, following behavioral evaluation, the rats were killed 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. Kainic acid had deleterious effects on cognitive behavior as kainic acid-injected rats on the control diet exhibited increased latencies to find a hidden platform in the Morris water maze compared to Ringer's buffer-injected rats and utilized non-spatial strategies during probe trials. The blueberry diet, and to a lesser degree the piroxicam diet, was able to improve cognitive performance. Immunohistochemical analyses of OX-6 expression revealed that kainic acid produced an inflammatory response by increasing the OX-6 positive areas in the hippocampus of kainic acid-injected rats. Kainic acid up-regulated the expression of the inflammatory cytokines IL-1beta and TNF-alpha, the neurotrophic factor IGF-1, and the transcription factor NF-kappaB. Blueberry and piroxicam supplementations were found to attenuate the kainic acid-induced increase in the expression of IL-1beta, TNF-alpha, and NF-kappaB, while only blueberry was able to augment the increased IGF-1 expression. These results indicate that blueberry polyphenols attenuate learning impairments following neurotoxic insult and exert anti-inflammatory actions, perhaps via alteration of gene expression.

Authors+Show Affiliations

USDA-ARS, Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts 02111, USA. barbara.shukitthale@ars.usda.govNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

18681986

Citation

Shukitt-Hale, Barbara, et al. "Blueberry Polyphenols Attenuate Kainic Acid-induced Decrements in Cognition and Alter Inflammatory Gene Expression in Rat Hippocampus." Nutritional Neuroscience, vol. 11, no. 4, 2008, pp. 172-82.
Shukitt-Hale B, Lau FC, Carey AN, et al. Blueberry polyphenols attenuate kainic acid-induced decrements in cognition and alter inflammatory gene expression in rat hippocampus. Nutr Neurosci. 2008;11(4):172-82.
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), 172-82. https://doi.org/10.1179/147683008X301487
Shukitt-Hale B, et al. Blueberry Polyphenols Attenuate Kainic Acid-induced Decrements in Cognition and Alter Inflammatory Gene Expression in Rat Hippocampus. Nutr Neurosci. 2008;11(4):172-82. PubMed PMID: 18681986.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Blueberry polyphenols attenuate kainic acid-induced decrements in cognition and alter inflammatory gene expression in rat hippocampus. AU - Shukitt-Hale,Barbara, AU - Lau,Francis C, AU - Carey,Amanda N, AU - Galli,Rachel L, AU - Spangler,Edward L, AU - Ingram,Donald K, AU - Joseph,James A, PY - 2008/8/7/pubmed PY - 2009/1/30/medline PY - 2008/8/7/entrez SP - 172 EP - 82 JF - Nutritional neuroscience JO - Nutr Neurosci VL - 11 IS - 4 N2 - 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 can reduce the deleterious effects of inflammation induced by central administration of kainic acid by altering the expression of genes associated with inflammation. To this end, 4-month-old male Fischer-344 (F344) rats were fed a control, 0.015% piroxicam (an NSAID) or 2% blueberry diet for 8 weeks before either Ringer's buffer or kainic acid was bilaterally micro-infused into the hippocampus. Two weeks later, following behavioral evaluation, the rats were killed 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. Kainic acid had deleterious effects on cognitive behavior as kainic acid-injected rats on the control diet exhibited increased latencies to find a hidden platform in the Morris water maze compared to Ringer's buffer-injected rats and utilized non-spatial strategies during probe trials. The blueberry diet, and to a lesser degree the piroxicam diet, was able to improve cognitive performance. Immunohistochemical analyses of OX-6 expression revealed that kainic acid produced an inflammatory response by increasing the OX-6 positive areas in the hippocampus of kainic acid-injected rats. Kainic acid up-regulated the expression of the inflammatory cytokines IL-1beta and TNF-alpha, the neurotrophic factor IGF-1, and the transcription factor NF-kappaB. Blueberry and piroxicam supplementations were found to attenuate the kainic acid-induced increase in the expression of IL-1beta, TNF-alpha, and NF-kappaB, while only blueberry was able to augment the increased IGF-1 expression. These results indicate that blueberry polyphenols attenuate learning impairments following neurotoxic insult and exert anti-inflammatory actions, perhaps via alteration of gene expression. SN - 1476-8305 UR - https://www.unboundmedicine.com/medline/citation/18681986/Blueberry_polyphenols_attenuate_kainic_acid_induced_decrements_in_cognition_and_alter_inflammatory_gene_expression_in_rat_hippocampus_ L2 - https://www.tandfonline.com/doi/full/10.1179/147683008X301487 DB - PRIME DP - Unbound Medicine ER -