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Alzheimer Disease and Selected Risk Factors Disrupt a Co-regulation of Monoamine Oxidase-A/B in the Hippocampus, but Not in the Cortex.

التفاصيل البيبلوغرافية
العنوان: Alzheimer Disease and Selected Risk Factors Disrupt a Co-regulation of Monoamine Oxidase-A/B in the Hippocampus, but Not in the Cortex.
المؤلفون: Quartey MO; Cell Signalling Laboratory, Department of Psychiatry, University of Saskatchewan, Saskatoon, SK, Canada., Nyarko JNK; Cell Signalling Laboratory, Department of Psychiatry, University of Saskatchewan, Saskatoon, SK, Canada., Pennington PR; Cell Signalling Laboratory, Department of Psychiatry, University of Saskatchewan, Saskatoon, SK, Canada., Heistad RM; Cell Signalling Laboratory, Department of Psychiatry, University of Saskatchewan, Saskatoon, SK, Canada., Klassen PC; The Pharmacology-Physiology Honours Program, University of Saskatchewan, Saskatoon, SK, Canada., Baker GB; Neurochemical Research Unit, Department of Psychiatry, University of Alberta, Edmonton, AB, Canada., Mousseau DD; Cell Signalling Laboratory, Department of Psychiatry, University of Saskatchewan, Saskatoon, SK, Canada.; The Pharmacology-Physiology Honours Program, University of Saskatchewan, Saskatoon, SK, Canada.
المصدر: Frontiers in neuroscience [Front Neurosci] 2018 Jun 26; Vol. 12, pp. 419. Date of Electronic Publication: 2018 Jun 26 (Print Publication: 2018).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Frontiers Research Foundation Country of Publication: Switzerland NLM ID: 101478481 Publication Model: eCollection Cited Medium: Print ISSN: 1662-4548 (Print) Linking ISSN: 1662453X NLM ISO Abbreviation: Front Neurosci Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Lausanne : Frontiers Research Foundation
مستخلص: Monoamine oxidase-A (MAO-A) and MAO-B have both been implicated in the pathology of Alzheimer disease (AD). We examined 60 autopsied control and AD donor brain samples to determine how well MAO function aligned with two major risk factors for AD, namely sex and APOE ε4 status. MAO-A activity was increased in AD cortical, but not hippocampal, samples. In contrast, MAO-B activity was increased in both regions (with a strong input from female donors) whether sample means were compared based on: (a) diagnosis alone; (b) diagnosis-by- APOE ε4 status (i.e., carriers vs. non-carriers of the ε4 allele); or (c) APOE ε4 status alone (i.e., ignoring 'diagnosis' as a variable). Sample means strictly based on the donor's sex did not reveal any difference in either MAO-A or MAO-B activity. Unexpectedly, we found that cortical MAO-A and MAO-B activities were highly correlated in both males and females (if focussing strictly on the donor's sex), while in the hippocampus, any correlation was lost in female samples. Stratifying for sex-by- APOE ε4 status revealed a strong correlation between cortical MAO-A and MAO-B activities in both non-carriers and carriers of the allele, but any correlation in hippocampal samples was lost in carriers of the allele. A diagnosis of AD disrupted the correlation between MAO-A and MAO-B activities in the hippocampus, but not the cortex. We observed a novel region-dependent co-regulation of MAO-A and MAO-B mRNAs (but not proteins), while a lack of correlation between MAO activities and the respective proteins corroborated previous reports. Overexpression of human APOE4 increased MAO activity (but not mRNA/protein) in C6 and in HT-22 cell cultures. We identified a novel co-regulation of MAO-A and MAO-B activities that is spared from any influence of risk factors for AD or AD itself in the cortex, but vulnerable to these same factors in the hippocampus. Sex- and region-dependent abilities to buffer influences on brain MAO activities could have significant bearing on ambiguous outcomes when monoaminergic systems are targeted in clinical populations.
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فهرسة مساهمة: Keywords: APOE4; Alzheimer disease; depression; monoamine oxidase; sex/gender risk
تواريخ الأحداث: Date Created: 20180713 Latest Revision: 20201001
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC6029266
DOI: 10.3389/fnins.2018.00419
PMID: 29997470
قاعدة البيانات: MEDLINE
الوصف
تدمد:1662-4548
DOI:10.3389/fnins.2018.00419