000137854 001__ 137854 000137854 005__ 20240321220328.0 000137854 0247_ $$2doi$$a10.1016/j.bbr.2015.01.040 000137854 0247_ $$2pmid$$apmid:25655513 000137854 0247_ $$2ISSN$$a0166-4328 000137854 0247_ $$2ISSN$$a1872-7549 000137854 0247_ $$2altmetric$$aaltmetric:52784158 000137854 037__ $$aDZNE-2020-04176 000137854 041__ $$aEnglish 000137854 082__ $$a610 000137854 1001_ $$0P:(DE-HGF)0$$aJadavji, Nafisa M$$b0$$eCorresponding author 000137854 245__ $$aElevated levels of plasma homocysteine, deficiencies in dietary folic acid and uracil-DNA glycosylase impair learning in a mouse model of vascular cognitive impairment. 000137854 260__ $$aAmsterdam$$bElsevier$$c2015 000137854 264_1 $$2Crossref$$3print$$bElsevier BV$$c2015-04-01 000137854 3367_ $$2DRIVER$$aarticle 000137854 3367_ $$2DataCite$$aOutput Types/Journal article 000137854 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1710430822_24479 000137854 3367_ $$2BibTeX$$aARTICLE 000137854 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000137854 3367_ $$00$$2EndNote$$aJournal Article 000137854 520__ $$aDietary deficiencies in folic acid result in elevated levels of plasma homocysteine, which has been associated with the development of dementia and other neurodegenerative disorders. Previously, we have shown that elevated levels of plasma homocysteine in mice deficient for a DNA repair enzyme, uracil-DNA glycosylase (UNG), result in neurodegeneration. The goal of this study was to evaluate how deficiencies in folic acid and UNG along with elevated levels of homocysteine affect vascular cognitive impairment, via chronic hypoperfursion in an animal model. Ung(+/+) and Ung(-/-) mice were placed on either control (CD) or folic acid deficient (FADD) diets. Six weeks later, the mice either underwent implantation of microcoils around both common carotid arteries. Post-operatively, behavioral tests began at 3-weeks, angiography was measured after 5-weeks using MRI to assess vasculature and at completion of study plasma and brain tissue was collected for analysis. Learning impairments in the Morris water maze (MWM) were observed only in hypoperfused Ung(-/-) FADD mice and these mice had significantly higher plasma homocysteine concentrations. Interestingly, Ung(+/+) FADD produced significant remodeling of the basilar artery and arterial vasculature. Increased expression of GFAP was observed in the dentate gyrus of Ung(-/-) hypoperfused and FADD sham mice. Chronic hypoperfusion resulted in increased cortical MMP-9 protein levels of FADD hypoperfused mice regardless of genotypes. These results suggest that elevated levels of homocysteine only, as a result of dietary folic acid deficiency, don't lead to memory impairments and neurobiochemical changes. Rather a combination of either chronic hypoperfusion or UNG deficiency is required. 000137854 536__ $$0G:(DE-HGF)POF3-344$$a344 - Clinical and Health Care Research (POF3-344)$$cPOF3-344$$fPOF III$$x0 000137854 542__ $$2Crossref$$i2015-04-01$$uhttps://www.elsevier.com/tdm/userlicense/1.0/ 000137854 588__ $$aDataset connected to CrossRef, PubMed, 000137854 650_7 $$2NLM Chemicals$$aGlial Fibrillary Acidic Protein 000137854 650_7 $$2NLM Chemicals$$aNerve Tissue Proteins 000137854 650_7 $$2NLM Chemicals$$aglial fibrillary astrocytic protein, mouse 000137854 650_7 $$00LVT1QZ0BA$$2NLM Chemicals$$aHomocysteine 000137854 650_7 $$0EC 3.2.2.-$$2NLM Chemicals$$aUracil-DNA Glycosidase 000137854 650_7 $$0EC 3.4.24.35$$2NLM Chemicals$$aMatrix Metalloproteinase 9 000137854 650_7 $$0EC 3.4.24.35$$2NLM Chemicals$$aMmp9 protein, mouse 000137854 650_2 $$2MeSH$$aAnimals 000137854 650_2 $$2MeSH$$aBasilar Artery: pathology 000137854 650_2 $$2MeSH$$aBasilar Artery: physiopathology 000137854 650_2 $$2MeSH$$aBrain: blood supply 000137854 650_2 $$2MeSH$$aBrain: pathology 000137854 650_2 $$2MeSH$$aBrain: physiopathology 000137854 650_2 $$2MeSH$$aCarotid Artery Diseases 000137854 650_2 $$2MeSH$$aCerebrovascular Disorders: pathology 000137854 650_2 $$2MeSH$$aCerebrovascular Disorders: physiopathology 000137854 650_2 $$2MeSH$$aChronic Disease 000137854 650_2 $$2MeSH$$aCognition Disorders: pathology 000137854 650_2 $$2MeSH$$aCognition Disorders: physiopathology 000137854 650_2 $$2MeSH$$aDiet 000137854 650_2 $$2MeSH$$aDisease Models, Animal 000137854 650_2 $$2MeSH$$aFemale 000137854 650_2 $$2MeSH$$aFolic Acid Deficiency: pathology 000137854 650_2 $$2MeSH$$aFolic Acid Deficiency: physiopathology 000137854 650_2 $$2MeSH$$aGlial Fibrillary Acidic Protein 000137854 650_2 $$2MeSH$$aGliosis: pathology 000137854 650_2 $$2MeSH$$aGliosis: physiopathology 000137854 650_2 $$2MeSH$$aHomocysteine: blood 000137854 650_2 $$2MeSH$$aLearning Disabilities: pathology 000137854 650_2 $$2MeSH$$aLearning Disabilities: physiopathology 000137854 650_2 $$2MeSH$$aMale 000137854 650_2 $$2MeSH$$aMatrix Metalloproteinase 9: metabolism 000137854 650_2 $$2MeSH$$aMaze Learning: physiology 000137854 650_2 $$2MeSH$$aMice, Inbred C57BL 000137854 650_2 $$2MeSH$$aMice, Knockout 000137854 650_2 $$2MeSH$$aNerve Tissue Proteins: metabolism 000137854 650_2 $$2MeSH$$aRandom Allocation 000137854 650_2 $$2MeSH$$aUracil-DNA Glycosidase: deficiency 000137854 650_2 $$2MeSH$$aUracil-DNA Glycosidase: genetics 000137854 7001_ $$aFarr, Tracy D$$b1 000137854 7001_ $$aLips, Janet$$b2 000137854 7001_ $$aKhalil, Ahmed A$$b3 000137854 7001_ $$aBoehm-Sturm, Philipp$$b4 000137854 7001_ $$0P:(DE-HGF)0$$aFoddis, Marco$$b5 000137854 7001_ $$aHarms, Christoph$$b6 000137854 7001_ $$0P:(DE-HGF)0$$aFüchtemeier, Martina$$b7 000137854 7001_ $$0P:(DE-2719)2810838$$aDirnagl, Ulrich$$b8$$eLast author$$udzne 000137854 77318 $$2Crossref$$3journal-article$$a10.1016/j.bbr.2015.01.040$$b : Elsevier BV, 2015-04-01$$p215-226$$tBehavioural Brain Research$$v283$$x0166-4328$$y2015 000137854 773__ $$0PERI:(DE-600)2013604-3$$a10.1016/j.bbr.2015.01.040$$gVol. 283, p. 215 - 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