PMID- 20937133 OWN - NLM STAT- MEDLINE DCOM- 20101206 LR - 20211020 IS - 1742-2094 (Electronic) IS - 1742-2094 (Linking) VI - 7 DP - 2010 Oct 11 TI - Cerebrovascular expression of proteins related to inflammation, oxidative stress and neurotoxicity is altered with aging. PG - 63 LID - 10.1186/1742-2094-7-63 [doi] AB - BACKGROUND: Most neurodegenerative diseases are age-related disorders; however, how aging predisposes the brain to disease has not been adequately addressed. The objective of this study is to determine whether expression of proteins in the cerebromicrovasculature related to inflammation, oxidative stress and neurotoxicity is altered with aging. METHODS: Brain microvessels are isolated from Fischer 344 rats at 6, 12, 18 and 24 months of age. Levels of interleukin (IL)-1beta and IL-6 RNA are determined by RT-PCR and release of cytokines into the media by ELISA. Vessel conditioned media are also screened by ELISA for IL-1alpha, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha, (TNFalpha), and interferon gamma (IFNgamma). Immunofluorescent analysis of brain sections for IL-1beta and IL-6 is performed. RESULTS: Expression of IL-1beta and IL-6, both at RNA and protein levels, significantly (p < 0.01) decreases with age. Levels of MCP-1, TNFalpha, IL-1alpha, and IFNgamma are significantly (p < 0.05-0.01) lower in 24 month old rats compared to 6 month old animals. Immunofluorescent analysis of brain vessels also shows a decline in IL-1beta and IL-6 in aged rats. An increase in oxidative stress, assessed by increased carbonyl formation, as well as a decrease in the antioxidant protein manganese superoxide dismutase (MnSOD) is evident in vessels of aged animals. Finally, addition of microvessel conditioned media from aged rats to neuronal cultures evokes significant (p < 0.001) neurotoxicity. CONCLUSIONS: These data demonstrate that cerebrovascular expression of proteins related to inflammation, oxidative stress and neurotoxicity is altered with aging and suggest that the microvasculature may contribute to functional changes in the aging brain. FAU - Tripathy, Debjani AU - Tripathy D AD - Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, Texas, USA. FAU - Yin, Xiangling AU - Yin X FAU - Sanchez, Alma AU - Sanchez A FAU - Luo, Jinhua AU - Luo J FAU - Martinez, Joseph AU - Martinez J FAU - Grammas, Paula AU - Grammas P LA - eng GR - AG020569/AG/NIA NIH HHS/United States GR - AG028367/AG/NIA NIH HHS/United States GR - AG15964/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20101011 PL - England TA - J Neuroinflammation JT - Journal of neuroinflammation JID - 101222974 RN - 0 (Chemokine CCL2) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-6) RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Aging/*metabolism MH - Analysis of Variance MH - Animals MH - Blotting, Western MH - Cell Death MH - Cells, Cultured MH - Cerebral Cortex/*metabolism MH - Chemokine CCL2/genetics/metabolism MH - Enzyme-Linked Immunosorbent Assay MH - Fluorescent Antibody Technique MH - Inflammation MH - Interferon-gamma/genetics/metabolism MH - Interleukin-1beta/genetics/*metabolism MH - Interleukin-6/genetics/*metabolism MH - Male MH - Microvessels/*metabolism MH - Neurons/cytology/metabolism MH - Oxidative Stress/physiology MH - RNA, Messenger/genetics/metabolism MH - Rats MH - Rats, Inbred F344 MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tumor Necrosis Factor-alpha/genetics/metabolism PMC - PMC2965134 EDAT- 2010/10/13 06:00 MHDA- 2010/12/14 06:00 PMCR- 2010/10/11 CRDT- 2010/10/13 06:00 PHST- 2010/07/01 00:00 [received] PHST- 2010/10/11 00:00 [accepted] PHST- 2010/10/13 06:00 [entrez] PHST- 2010/10/13 06:00 [pubmed] PHST- 2010/12/14 06:00 [medline] PHST- 2010/10/11 00:00 [pmc-release] AID - 1742-2094-7-63 [pii] AID - 10.1186/1742-2094-7-63 [doi] PST - epublish SO - J Neuroinflammation. 2010 Oct 11;7:63. doi: 10.1186/1742-2094-7-63.