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Intrahippocampal administration of amyloid-β(1-42) oligomers acutely impairs spatial working memory, insulin signaling, and hippocampal metabolism.
J Alzheimers Dis 2012; 30(2):413-22JA

Abstract

Increasing evidence suggests that abnormal brain accumulation of amyloid-β(1-42) (Aβ(1-42)) oligomers plays a causal role in Alzheimer's disease (AD), and in particular may cause the cognitive deficits that are the hallmark of AD. In vitro, Aβ(1-42) oligomers impair insulin signaling and suppress neural functioning. We previously showed that endogenous insulin signaling is an obligatory component of normal hippocampal function, and that disrupting this signaling led to a rapid impairment of spatial working memory, while delivery of exogenous insulin to the hippocampus enhanced both memory and metabolism; diet-induced insulin resistance both impaired spatial memory and prevented insulin from increasing metabolism or cognitive function. Hence, we tested the hypothesis that Aβ(1-42) oligomers could acutely impair hippocampal metabolic and cognitive processes in vivo in the rat. Our findings support this hypothesis: Aβ(1-42) oligomers impaired spontaneous alternation behavior while preventing the task-associated dip in hippocampal ECF glucose observed in control animals. In addition, Aβ(1-42) oligomers decreased plasma membrane translocation of the insulin-sensitive glucose transporter 4 (GluT4), and impaired insulin signaling as measured by phosphorylation of Akt. These data show in vivo that Aβ(1-42) oligomers can rapidly impair hippocampal cognitive and metabolic processes, and provide support for the hypothesis that elevated Aβ(1-42) leads to cognitive impairment via interference with hippocampal insulin signaling.

Authors+Show Affiliations

Behavioral Neuroscience, University at Albany, Albany, NY, USA. jp973156@albany.edu

Pub Type(s)

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

Language

eng

PubMed ID

22430529

Citation

Pearson-Leary, Jiah, and Ewan C. McNay. "Intrahippocampal Administration of Amyloid-β(1-42) Oligomers Acutely Impairs Spatial Working Memory, Insulin Signaling, and Hippocampal Metabolism." Journal of Alzheimer's Disease : JAD, vol. 30, no. 2, 2012, pp. 413-22.
Pearson-Leary J, McNay EC. Intrahippocampal administration of amyloid-β(1-42) oligomers acutely impairs spatial working memory, insulin signaling, and hippocampal metabolism. J Alzheimers Dis. 2012;30(2):413-22.
Pearson-Leary, J., & McNay, E. C. (2012). Intrahippocampal administration of amyloid-β(1-42) oligomers acutely impairs spatial working memory, insulin signaling, and hippocampal metabolism. Journal of Alzheimer's Disease : JAD, 30(2), pp. 413-22. doi:10.3233/JAD-2012-112192.
Pearson-Leary J, McNay EC. Intrahippocampal Administration of Amyloid-β(1-42) Oligomers Acutely Impairs Spatial Working Memory, Insulin Signaling, and Hippocampal Metabolism. J Alzheimers Dis. 2012;30(2):413-22. PubMed PMID: 22430529.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intrahippocampal administration of amyloid-β(1-42) oligomers acutely impairs spatial working memory, insulin signaling, and hippocampal metabolism. AU - Pearson-Leary,Jiah, AU - McNay,Ewan C, PY - 2012/3/21/entrez PY - 2012/3/21/pubmed PY - 2012/9/19/medline SP - 413 EP - 22 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 30 IS - 2 N2 - Increasing evidence suggests that abnormal brain accumulation of amyloid-β(1-42) (Aβ(1-42)) oligomers plays a causal role in Alzheimer's disease (AD), and in particular may cause the cognitive deficits that are the hallmark of AD. In vitro, Aβ(1-42) oligomers impair insulin signaling and suppress neural functioning. We previously showed that endogenous insulin signaling is an obligatory component of normal hippocampal function, and that disrupting this signaling led to a rapid impairment of spatial working memory, while delivery of exogenous insulin to the hippocampus enhanced both memory and metabolism; diet-induced insulin resistance both impaired spatial memory and prevented insulin from increasing metabolism or cognitive function. Hence, we tested the hypothesis that Aβ(1-42) oligomers could acutely impair hippocampal metabolic and cognitive processes in vivo in the rat. Our findings support this hypothesis: Aβ(1-42) oligomers impaired spontaneous alternation behavior while preventing the task-associated dip in hippocampal ECF glucose observed in control animals. In addition, Aβ(1-42) oligomers decreased plasma membrane translocation of the insulin-sensitive glucose transporter 4 (GluT4), and impaired insulin signaling as measured by phosphorylation of Akt. These data show in vivo that Aβ(1-42) oligomers can rapidly impair hippocampal cognitive and metabolic processes, and provide support for the hypothesis that elevated Aβ(1-42) leads to cognitive impairment via interference with hippocampal insulin signaling. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/22430529/Intrahippocampal_administration_of_amyloid_β_1_42__oligomers_acutely_impairs_spatial_working_memory_insulin_signaling_and_hippocampal_metabolism_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-2012-112192 DB - PRIME DP - Unbound Medicine ER -