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Genetic reductions of beta-site amyloid precursor protein-cleaving enzyme 1 and amyloid-beta ameliorate impairment of conditioned taste aversion memory in 5XFAD Alzheimer's disease model mice.
Eur J Neurosci 2010; 31(1):110-8EJ

Abstract

Although transgenic mouse models of Alzheimer's disease (AD) recapitulate amyloid-beta (Abeta)-related pathologies and cognitive impairments, previous studies have mainly evaluated their hippocampus-dependent memory dysfunctions using behavioral tasks such as the water maze and fear conditioning. However, multiple memory systems become impaired in AD as the disease progresses and it is important to test whether other forms of memory are affected in AD models. This study was designed to use conditioned taste aversion (CTA) and contextual fear conditioning paradigms to compare the phenotypes of hippocampus-independent and -dependent memory functions, respectively, in 5XFAD amyloid precursor protein/presenilin-1 transgenic mice that harbor five familial AD mutations. Although both types of memory were significantly impaired in 5XFAD mice, the onset of CTA memory deficits (approximately 9 months of age) was delayed compared with that of contextual memory deficits (approximately 6 months of age). Furthermore, 5XFAD mice that were genetically engineered to have reduced levels of beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) (BACE1(+/-).5XFAD) exhibited improved CTA memory, which was equivalent to the performance of wild-type controls. Importantly, elevated levels of cerebral beta-secretase-cleaved C-terminal fragment (C99) and Abeta peptides in 5XFAD mice were significantly reduced in BACE1(+/-).5XFAD mice. Furthermore, Abeta deposition in the insular cortex and basolateral amygdala, two brain regions that are critically involved in CTA performance, was also reduced in BACE1(+/-).5XFAD compared with 5XFAD mice. Our findings indicate that the CTA paradigm is useful for evaluating a hippocampus-independent form of memory defect in AD model mice, which is sensitive to rescue by partial reductions of the beta-secretase BACE1 and consequently of cerebral Abeta.

Authors+Show Affiliations

Center for Dementia Research, Nathan Kline Institute, New York University School of Medicine, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20092558

Citation

Devi, Latha, and Masuo Ohno. "Genetic Reductions of Beta-site Amyloid Precursor Protein-cleaving Enzyme 1 and Amyloid-beta Ameliorate Impairment of Conditioned Taste Aversion Memory in 5XFAD Alzheimer's Disease Model Mice." The European Journal of Neuroscience, vol. 31, no. 1, 2010, pp. 110-8.
Devi L, Ohno M. Genetic reductions of beta-site amyloid precursor protein-cleaving enzyme 1 and amyloid-beta ameliorate impairment of conditioned taste aversion memory in 5XFAD Alzheimer's disease model mice. Eur J Neurosci. 2010;31(1):110-8.
Devi, L., & Ohno, M. (2010). Genetic reductions of beta-site amyloid precursor protein-cleaving enzyme 1 and amyloid-beta ameliorate impairment of conditioned taste aversion memory in 5XFAD Alzheimer's disease model mice. The European Journal of Neuroscience, 31(1), pp. 110-8. doi:10.1111/j.1460-9568.2009.07031.x.
Devi L, Ohno M. Genetic Reductions of Beta-site Amyloid Precursor Protein-cleaving Enzyme 1 and Amyloid-beta Ameliorate Impairment of Conditioned Taste Aversion Memory in 5XFAD Alzheimer's Disease Model Mice. Eur J Neurosci. 2010;31(1):110-8. PubMed PMID: 20092558.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic reductions of beta-site amyloid precursor protein-cleaving enzyme 1 and amyloid-beta ameliorate impairment of conditioned taste aversion memory in 5XFAD Alzheimer's disease model mice. AU - Devi,Latha, AU - Ohno,Masuo, Y1 - 2009/12/21/ PY - 2010/1/23/entrez PY - 2010/1/23/pubmed PY - 2010/4/17/medline SP - 110 EP - 8 JF - The European journal of neuroscience JO - Eur. J. Neurosci. VL - 31 IS - 1 N2 - Although transgenic mouse models of Alzheimer's disease (AD) recapitulate amyloid-beta (Abeta)-related pathologies and cognitive impairments, previous studies have mainly evaluated their hippocampus-dependent memory dysfunctions using behavioral tasks such as the water maze and fear conditioning. However, multiple memory systems become impaired in AD as the disease progresses and it is important to test whether other forms of memory are affected in AD models. This study was designed to use conditioned taste aversion (CTA) and contextual fear conditioning paradigms to compare the phenotypes of hippocampus-independent and -dependent memory functions, respectively, in 5XFAD amyloid precursor protein/presenilin-1 transgenic mice that harbor five familial AD mutations. Although both types of memory were significantly impaired in 5XFAD mice, the onset of CTA memory deficits (approximately 9 months of age) was delayed compared with that of contextual memory deficits (approximately 6 months of age). Furthermore, 5XFAD mice that were genetically engineered to have reduced levels of beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) (BACE1(+/-).5XFAD) exhibited improved CTA memory, which was equivalent to the performance of wild-type controls. Importantly, elevated levels of cerebral beta-secretase-cleaved C-terminal fragment (C99) and Abeta peptides in 5XFAD mice were significantly reduced in BACE1(+/-).5XFAD mice. Furthermore, Abeta deposition in the insular cortex and basolateral amygdala, two brain regions that are critically involved in CTA performance, was also reduced in BACE1(+/-).5XFAD compared with 5XFAD mice. Our findings indicate that the CTA paradigm is useful for evaluating a hippocampus-independent form of memory defect in AD model mice, which is sensitive to rescue by partial reductions of the beta-secretase BACE1 and consequently of cerebral Abeta. SN - 1460-9568 UR - https://www.unboundmedicine.com/medline/citation/20092558/Genetic_reductions_of_beta_site_amyloid_precursor_protein_cleaving_enzyme_1_and_amyloid_beta_ameliorate_impairment_of_conditioned_taste_aversion_memory_in_5XFAD_Alzheimer's_disease_model_mice_ L2 - https://doi.org/10.1111/j.1460-9568.2009.07031.x DB - PRIME DP - Unbound Medicine ER -