Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Alzheimer's model and vitamin D

ABSTRACT: Little is known about the global molecular changes leading to neurodegeneration and brain dysfunction in Alzheimer's disease (AD). To study the molecular cascades involved, we chose to study the transcriptomic profile of an early-onset AD model, the 5xFAD mice, at different time points (1 month, 4 months, 6 months and 9 months) of the disease. We are also interested in the effects of vitamin D supplementation in AD. Vitamin D receptor belongs to the family of nuclear receptors and vitamin D can act as a neurosteroid by regulating the expression of over a 1000 genes. We therefore decided to evaluate the effect of vitamin D supplementation in this AD mouse model at the transcriptomic level, after 5 months of supplementation (i.e. from 1 month to 6 months and from 4 months to 9 months).

ORGANISM(S): Mus musculus

SUBMITTER: Verena Landel

PROVIDER: E-MTAB-1937 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Temporal gene profiling of the 5XFAD transgenic mouse model highlights the importance of microglial activation in Alzheimer's disease.

Landel Véréna V Baranger Kévin K Virard Isabelle I Loriod Béatrice B Khrestchatisky Michel M Rivera Santiago S Benech Philippe P Féron François F

Molecular neurodegeneration 20140911

<h4>Background</h4>The 5XFAD early onset mouse model of Alzheimer's disease (AD) is gaining momentum. Behavioral, electrophysiological and anatomical studies have identified age-dependent alterations that can be reminiscent of human AD. However, transcriptional changes during disease progression have not yet been investigated. To this end, we carried out a transcriptomic analysis on RNAs from the neocortex and the hippocampus of 5XFAD female mice at the ages of one, four, six and nine months (M1 ...[more]

PMID: 25213090

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Project description:Extracellular senile plaques of amyloid beta (Abeta) are a pathological hallmark in brain of patients with Alzheimer`s Disease (AD). Abeta is generated by the amyloidogenic processing of the amyloid precursor protein (APP). Concomitant to Abeta load, AD brain is characterized by an increase in protein level and activity of the angiotensin-converting enzyme (ACE). ACE inhibitors are a widely used class of drugs with established benefits for patients with cardiovascular disease. However, the role of ACE and ACE inhibition in the development of Abeta plaques and the process of AD-related neurodegeneration is not clear since ACE was reported to degrade Abeta. To investigate the effect of ACE inhibition on AD-related pathomechanisms, we used Tg2576 mice with neuron-specific expression of APPSwe as AD model. From 12 months of age, substantial Abeta plaque load accumulates in the hippocampus of Tg2576 mice as a brain region, which is highly vulnerable to AD-related neurodegeneration. The effect of central ACE inhibition was studied by treatment of 12 month-old Tg2576 mice for six months with the brain penetrating ACE inhibitor captopril. At an age of 18 months, hippocampal gene expression profiling was performed of captopril-treated Tg2576 mice relative to untreated 18 month-old Tg2576 controls with high Abeta plaque load. As an additional control, we used 12 month-old Tg2576 mice with low Abeta plaque load. Whole genome microarray gene expression profiling revealed gene expression changes induced by the brain-penetrating ACE inhibitor captopril, which could reflect the neuro-regenerative potential of central ACE inhibition. Microarray gene expression profiling was performed of hippocampi isolated from aged, 18 month-old Tg2576 (APPSwe-transgenic) AD mice with high Abeta plaque load relative to age-matched Tg2576 mice, which were treated for 6 months with the centrally active ACE inhibitor captopril. Another study group consisted of 12 month-old Tg2576 mice with low Abeta plaque load. In total, three study groups were analyzed, i.e. (i) 18 month-old untreated Tg2576 mice with high Abeta plaque load, (ii) age-matched Tg2576 mice treated for 6 months with the brain-penetrating ACE inhibitor captopril (20 mg/kg body weight/day in drinking water), and (iii) untreated 12 month-old Tg2576 mice with low Abeta plaque load reflecting the time point when captopril treatment was initiated. Two biological replicates were made of each group, and total hippocampal RNA of four mice was pooled for one gene chip.

Dataset Information

Alzheimer's model and vitamin D

Publications

Temporal gene profiling of the 5XFAD transgenic mouse model highlights the importance of microglial activation in Alzheimer's disease.

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