| Age-dependent changes in noradrenergic locus coeruleus system in wild-type and APP23 transgenic mice. | |
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MedLine Citation:
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PMID: 19631722 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Alzheimer's disease (AD), a neurodegenerative disorder, is characterized by the loss of neurons in specific regions of the CNS including the locus coeruleus (LC), the major noradrenergic locus in the CNS. Several animal models of AD have been developed that exhibit some of the pathophysiological changes in the CNS that are observed in AD patients. The purpose of this study was to determine if the integrity of the LC noradrenergic system is altered in the amyloid precursor protein 23 (APP23) mouse model of AD at the age of 3, 6 and 12 months through quantification of tyrosine hydroxylase (TH) mRNA expression. Despite a previous study suggesting alterations in the noradrenergic transmission system of APP23 mice, the current study failed to show altered TH-positive neuronal numbers or expression in LC noradrenergic neurons of APP23 mice versus wild-type (WT) littermates. However, the present study did demonstrate an age-dependent effect on TH mRNA expression. Both the number of TH-containing neurons and the amount of TH-positive grains/neuron significantly increased between the age of 3 and 6 months with no difference between 6 and 12 months. These observations indicate that any study comparing the noradrenergic system between WT (C57Bl/6) and experimental mice must strictly choose the age to be tested and limit age differences between control and experimental groups to the absolute minimum. More importantly, when long-term therapeutic interventions targeting the noradrenergic system are applied to mouse models, and related parameters are studied longitudinally, care should be taken to distinguish between potential therapeutic and strain-specific developmental or age-related alterations. |
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Authors:
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Patricia Szot; Debby Van Dam; Sylvia S White; Allyn Franklin; Matthias Staufenbiel; Peter Paul De Deyn |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2009-07-23 |
Journal Detail:
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Title: Neuroscience letters Volume: 463 ISSN: 1872-7972 ISO Abbreviation: Neurosci. Lett. Publication Date: 2009 Sep |
Date Detail:
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Created Date: 2009-08-11 Completed Date: 2009-10-23 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7600130 Medline TA: Neurosci Lett Country: Ireland |
Other Details:
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Languages: eng Pagination: 93-7 Citation Subset: IM |
Affiliation:
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Northwest Network for Mental Illness Research, Education, and Clinical Center, Veterans Administration Puget Sound Health Care System, and Department of Psychiatry and Behavioral Science, University of Washington, Seattle 98195, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aging
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metabolism* Amyloid beta-Protein Precursor / genetics* Animals Locus Coeruleus / cytology, metabolism* Male Mice Mice, Inbred C57BL Mice, Transgenic Neurons / cytology, enzymology Norepinephrine / metabolism* RNA, Messenger / biosynthesis Tyrosine 3-Monooxygenase / biosynthesis, genetics |
| Chemical | |
Reg. No./Substance:
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0/Amyloid beta-Protein Precursor; 0/RNA, Messenger; 51-41-2/Norepinephrine; EC 1.14.16.2/Tyrosine 3-Monooxygenase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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