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Suppression of nuclear factor kappa B ameliorates astrogliosis but not amyloid burden in APPswe/PS1dE9 mice.
Neuroscience 2009; 161(1):53-8N

Abstract

Neuroinflammation has been linked to the pathologies of Alzheimer's disease (AD), however, its effects on beta-amyloid (Abeta) burden are unclear. This study investigated the role of nuclear factor kappa B (NF-kappaB) in regulating neuroinflammation and Abeta deposition in a transgenic mouse model of AD. The APPswe/PS1dE9 mice and their wild-type controls received either the NF-kappaB inhibitor pyrrolidine dithiocarbamate (PDTC, i.p. 50 mg/kg daily) or saline starting at 7 months of age for 5 months. Expression of cyclooxygenase-2 (COX-2), tissue necrosis factor alpha (TNFalpha) precursor protein and microtubule-associated protein 2 was determined, and astrogliosis was assessed. Hippocampal and cortical levels of Abeta(1-40) and Abeta(1-42) were measured using ELISA. PDTC treatment effectively suppressed NF-kappaB signaling in APPswe/PS1dE9 mice as evidenced by the abolishment of COX-2 and TNFalpha induction. Inhibition of NF-kappaB further attenuated astrogliosis in the transgenic AD mice, yet markedly increased cerebral Abeta(1-42) burden. Our findings suggest that NF-kappaB can mediate induction of COX-2, TNFalpha and astrogliosis in APPswe/PS1dE9 mice. Additionally, these results support the idea that neuroinflammation contributes to the clearance of Abeta.

Authors+Show Affiliations

Division of Pharmaceutical Sciences and Graduate Neuroscience Program, University of Wyoming, College of Health Sciences, Department 3375, 1000 East University Avenue, Laramie, WY 82071-3375, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

19286451

Citation

Zhang, X, et al. "Suppression of Nuclear Factor Kappa B Ameliorates Astrogliosis but Not Amyloid Burden in APPswe/PS1dE9 Mice." Neuroscience, vol. 161, no. 1, 2009, pp. 53-8.
Zhang X, Luhrs KJ, Ryff KA, et al. Suppression of nuclear factor kappa B ameliorates astrogliosis but not amyloid burden in APPswe/PS1dE9 mice. Neuroscience. 2009;161(1):53-8.
Zhang, X., Luhrs, K. J., Ryff, K. A., Malik, W. T., Driscoll, M. J., & Culver, B. (2009). Suppression of nuclear factor kappa B ameliorates astrogliosis but not amyloid burden in APPswe/PS1dE9 mice. Neuroscience, 161(1), pp. 53-8. doi:10.1016/j.neuroscience.2009.03.010.
Zhang X, et al. Suppression of Nuclear Factor Kappa B Ameliorates Astrogliosis but Not Amyloid Burden in APPswe/PS1dE9 Mice. Neuroscience. 2009 Jun 16;161(1):53-8. PubMed PMID: 19286451.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Suppression of nuclear factor kappa B ameliorates astrogliosis but not amyloid burden in APPswe/PS1dE9 mice. AU - Zhang,X, AU - Luhrs,K J, AU - Ryff,K A, AU - Malik,W T, AU - Driscoll,M J, AU - Culver,B, Y1 - 2009/03/13/ PY - 2008/10/21/received PY - 2009/03/04/revised PY - 2009/03/05/accepted PY - 2009/3/17/entrez PY - 2009/3/17/pubmed PY - 2009/9/22/medline SP - 53 EP - 8 JF - Neuroscience JO - Neuroscience VL - 161 IS - 1 N2 - Neuroinflammation has been linked to the pathologies of Alzheimer's disease (AD), however, its effects on beta-amyloid (Abeta) burden are unclear. This study investigated the role of nuclear factor kappa B (NF-kappaB) in regulating neuroinflammation and Abeta deposition in a transgenic mouse model of AD. The APPswe/PS1dE9 mice and their wild-type controls received either the NF-kappaB inhibitor pyrrolidine dithiocarbamate (PDTC, i.p. 50 mg/kg daily) or saline starting at 7 months of age for 5 months. Expression of cyclooxygenase-2 (COX-2), tissue necrosis factor alpha (TNFalpha) precursor protein and microtubule-associated protein 2 was determined, and astrogliosis was assessed. Hippocampal and cortical levels of Abeta(1-40) and Abeta(1-42) were measured using ELISA. PDTC treatment effectively suppressed NF-kappaB signaling in APPswe/PS1dE9 mice as evidenced by the abolishment of COX-2 and TNFalpha induction. Inhibition of NF-kappaB further attenuated astrogliosis in the transgenic AD mice, yet markedly increased cerebral Abeta(1-42) burden. Our findings suggest that NF-kappaB can mediate induction of COX-2, TNFalpha and astrogliosis in APPswe/PS1dE9 mice. Additionally, these results support the idea that neuroinflammation contributes to the clearance of Abeta. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/19286451/Suppression_of_nuclear_factor_kappa_B_ameliorates_astrogliosis_but_not_amyloid_burden_in_APPswe/PS1dE9_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(09)00363-7 DB - PRIME DP - Unbound Medicine ER -