Gene expression parallels synaptic excitability and plasticity changes in Alzheimer´s disease
Alzheimer´s disease (AD) is a neurodegenerative disorder characterized by abnormal accumulation of β-amyloid and tau and synapse dysfunction in memory-related neural circuits. Pathological and functional changes in the medial temporal lobe, a region essential for explicit memory encoding, contribute...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2015-08-01
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| Series: | Frontiers in Cellular Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fncel.2015.00318/full |
| _version_ | 1818898251974180864 |
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| author | Carlos A Saura Arnaldo eParra-Damas Lilian eEnríquez-Barreto |
| author_facet | Carlos A Saura Arnaldo eParra-Damas Lilian eEnríquez-Barreto |
| author_sort | Carlos A Saura |
| collection | DOAJ |
| description | Alzheimer´s disease (AD) is a neurodegenerative disorder characterized by abnormal accumulation of β-amyloid and tau and synapse dysfunction in memory-related neural circuits. Pathological and functional changes in the medial temporal lobe, a region essential for explicit memory encoding, contribute to cognitive decline in AD. Surprisingly, functional imaging studies show increased activity of the hippocampus and associated cortical regions during memory tasks in presymptomatic and early AD stages, whereas brain activity declines as the disease progresses. These findings suggest an emerging scenario where early pathogenic events increase neuronal excitability leading to enhanced brain activity before clinical manifestations of the disease, a stage that is followed by decreased brain activity as neurodegeneration progresses. The mechanisms linking pathology with synaptic excitability and plasticity changes leading to memory loss in AD remain largely unclear. Recent studies suggest that increased brain activity parallels enhanced expression of genes involved in synaptic transmission and plasticity in preclinical stages, whereas expression of synaptic and activity-dependent genes are reduced by the onset of pathological and cognitive symptoms. Here, we review recent evidences indicating a relationship between transcriptional deregulation of synaptic genes and neuronal activity and memory loss in AD and mouse models. These findings provide the basis for potential clinical applications of memory-related transcriptional programs and their regulatory mechanisms as novel biomarkers and therapeutic targets to restore brain function in AD and other cognitive disorders. |
| first_indexed | 2024-12-19T19:29:07Z |
| format | Article |
| id | doaj.art-7782fb5a192b4997aece7d14028e730f |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-19T19:29:07Z |
| publishDate | 2015-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-7782fb5a192b4997aece7d14028e730f2022-12-21T20:08:41ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022015-08-01910.3389/fncel.2015.00318152848Gene expression parallels synaptic excitability and plasticity changes in Alzheimer´s diseaseCarlos A Saura0Arnaldo eParra-Damas1Lilian eEnríquez-Barreto2Universitat Autónoma de BarcelonaUniversitat Autónoma de BarcelonaUniversitat Autónoma de BarcelonaAlzheimer´s disease (AD) is a neurodegenerative disorder characterized by abnormal accumulation of β-amyloid and tau and synapse dysfunction in memory-related neural circuits. Pathological and functional changes in the medial temporal lobe, a region essential for explicit memory encoding, contribute to cognitive decline in AD. Surprisingly, functional imaging studies show increased activity of the hippocampus and associated cortical regions during memory tasks in presymptomatic and early AD stages, whereas brain activity declines as the disease progresses. These findings suggest an emerging scenario where early pathogenic events increase neuronal excitability leading to enhanced brain activity before clinical manifestations of the disease, a stage that is followed by decreased brain activity as neurodegeneration progresses. The mechanisms linking pathology with synaptic excitability and plasticity changes leading to memory loss in AD remain largely unclear. Recent studies suggest that increased brain activity parallels enhanced expression of genes involved in synaptic transmission and plasticity in preclinical stages, whereas expression of synaptic and activity-dependent genes are reduced by the onset of pathological and cognitive symptoms. Here, we review recent evidences indicating a relationship between transcriptional deregulation of synaptic genes and neuronal activity and memory loss in AD and mouse models. These findings provide the basis for potential clinical applications of memory-related transcriptional programs and their regulatory mechanisms as novel biomarkers and therapeutic targets to restore brain function in AD and other cognitive disorders.http://journal.frontiersin.org/Journal/10.3389/fncel.2015.00318/fullAmyloidGene Expression RegulationMemory DisordersTranscriptomeAlzheimer's diseaseCREB |
| spellingShingle | Carlos A Saura Arnaldo eParra-Damas Lilian eEnríquez-Barreto Gene expression parallels synaptic excitability and plasticity changes in Alzheimer´s disease Frontiers in Cellular Neuroscience Amyloid Gene Expression Regulation Memory Disorders Transcriptome Alzheimer's disease CREB |
| title | Gene expression parallels synaptic excitability and plasticity changes in Alzheimer´s disease |
| title_full | Gene expression parallels synaptic excitability and plasticity changes in Alzheimer´s disease |
| title_fullStr | Gene expression parallels synaptic excitability and plasticity changes in Alzheimer´s disease |
| title_full_unstemmed | Gene expression parallels synaptic excitability and plasticity changes in Alzheimer´s disease |
| title_short | Gene expression parallels synaptic excitability and plasticity changes in Alzheimer´s disease |
| title_sort | gene expression parallels synaptic excitability and plasticity changes in alzheimer 180 s disease |
| topic | Amyloid Gene Expression Regulation Memory Disorders Transcriptome Alzheimer's disease CREB |
| url | http://journal.frontiersin.org/Journal/10.3389/fncel.2015.00318/full |
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