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Retinoic acid attenuates beta-amyloid deposition and rescues memory deficits in an Alzheimer's disease transgenic mouse model.
J Neurosci. 2008 Nov 05; 28(45):11622-34.JN

Abstract

Recent studies have revealed that disruption of vitamin A signaling observed in Alzheimer's disease (AD) leads to beta-amyloid (Abeta) accumulation and memory deficits in rodents. The aim of the present study was to evaluate the therapeutic effect of all-trans retinoic acid (ATRA), an active metabolite of vitamin A, on the neuropathology and deficits of spatial learning and memory in amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic mice, a well established AD mouse model. Here we report a robust decrease in brain Abeta deposition and tau phosphorylation in the blinded study of APP/PS1 transgenic mice treated intraperitoneally for 8 weeks with ATRA (20 mg/kg, three times weekly, initiated when the mice were 5 months old). This was accompanied by a significant decrease in the APP phosphorylation and processing. The activity of cyclin-dependent kinase 5, a major kinase involved in both APP and tau phosphorylation, was markedly downregulated by ATRA treatment. The ATRA-treated APP/PS1 mice showed decreased activation of microglia and astrocytes, attenuated neuronal degeneration, and improved spatial learning and memory compared with the vehicle-treated APP/PS1 mice. These results support ATRA as an effective therapeutic agent for the prevention and treatment of AD.

Authors+Show Affiliations

Department of Veterans Affairs Medical Center, Richmond, Virginia 23249, USA.No affiliation info availableNo affiliation info availableNo 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, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

18987198

Citation

Ding, Yun, et al. "Retinoic Acid Attenuates Beta-amyloid Deposition and Rescues Memory Deficits in an Alzheimer's Disease Transgenic Mouse Model." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 28, no. 45, 2008, pp. 11622-34.
Ding Y, Qiao A, Wang Z, et al. Retinoic acid attenuates beta-amyloid deposition and rescues memory deficits in an Alzheimer's disease transgenic mouse model. J Neurosci. 2008;28(45):11622-34.
Ding, Y., Qiao, A., Wang, Z., Goodwin, J. S., Lee, E. S., Block, M. L., Allsbrook, M., McDonald, M. P., & Fan, G. H. (2008). Retinoic acid attenuates beta-amyloid deposition and rescues memory deficits in an Alzheimer's disease transgenic mouse model. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 28(45), 11622-34. https://doi.org/10.1523/JNEUROSCI.3153-08.2008
Ding Y, et al. Retinoic Acid Attenuates Beta-amyloid Deposition and Rescues Memory Deficits in an Alzheimer's Disease Transgenic Mouse Model. J Neurosci. 2008 Nov 5;28(45):11622-34. PubMed PMID: 18987198.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Retinoic acid attenuates beta-amyloid deposition and rescues memory deficits in an Alzheimer's disease transgenic mouse model. AU - Ding,Yun, AU - Qiao,Aimin, AU - Wang,Ziqing, AU - Goodwin,J Shawn, AU - Lee,Eun-Sook, AU - Block,Michelle L, AU - Allsbrook,Matthew, AU - McDonald,Michael P, AU - Fan,Guo-Huang, PY - 2008/11/7/pubmed PY - 2009/1/1/medline PY - 2008/11/7/entrez SP - 11622 EP - 34 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J Neurosci VL - 28 IS - 45 N2 - Recent studies have revealed that disruption of vitamin A signaling observed in Alzheimer's disease (AD) leads to beta-amyloid (Abeta) accumulation and memory deficits in rodents. The aim of the present study was to evaluate the therapeutic effect of all-trans retinoic acid (ATRA), an active metabolite of vitamin A, on the neuropathology and deficits of spatial learning and memory in amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic mice, a well established AD mouse model. Here we report a robust decrease in brain Abeta deposition and tau phosphorylation in the blinded study of APP/PS1 transgenic mice treated intraperitoneally for 8 weeks with ATRA (20 mg/kg, three times weekly, initiated when the mice were 5 months old). This was accompanied by a significant decrease in the APP phosphorylation and processing. The activity of cyclin-dependent kinase 5, a major kinase involved in both APP and tau phosphorylation, was markedly downregulated by ATRA treatment. The ATRA-treated APP/PS1 mice showed decreased activation of microglia and astrocytes, attenuated neuronal degeneration, and improved spatial learning and memory compared with the vehicle-treated APP/PS1 mice. These results support ATRA as an effective therapeutic agent for the prevention and treatment of AD. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/18987198/Retinoic_acid_attenuates_beta_amyloid_deposition_and_rescues_memory_deficits_in_an_Alzheimer's_disease_transgenic_mouse_model_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=18987198 DB - PRIME DP - Unbound Medicine ER -