Tau Depletion in APP Transgenic Mice Attenuates Task-Related Hyperactivation of the Hippocampus and Differentially Influences Locomotor Activity and Spatial Memory
Hippocampal hyperactivity, ascribed to amyloid β (Aβ)-induced imbalances in neural excitation and inhibition, is found in patients with mild cognitive impairment, a prodromal stage of Alzheimer's disease (AD). To better understand the relationship between hippocampal hyperactivity and the molec...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-03-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fnins.2018.00124/full |
| _version_ | 1817971213347061760 |
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| author | Misato Yoshikawa Misato Yoshikawa Yoshiyuki Soeda Yoshiyuki Soeda Makoto Michikawa Osborne F. X. Almeida Akihiko Takashima Akihiko Takashima |
| author_facet | Misato Yoshikawa Misato Yoshikawa Yoshiyuki Soeda Yoshiyuki Soeda Makoto Michikawa Osborne F. X. Almeida Akihiko Takashima Akihiko Takashima |
| author_sort | Misato Yoshikawa |
| collection | DOAJ |
| description | Hippocampal hyperactivity, ascribed to amyloid β (Aβ)-induced imbalances in neural excitation and inhibition, is found in patients with mild cognitive impairment, a prodromal stage of Alzheimer's disease (AD). To better understand the relationship between hippocampal hyperactivity and the molecular triggers of behavioral impairments in AD, we used Mn-enhanced MRI (MEMRI) to assess neuronal activity after subjecting mice to a task requiring spatial learning and memory. Depletion of endogenous tau in an amyloid precursor protein (APP) transgenic (J20) mouse line was shown to ameliorate hippocampal hyperactivity in J20 animals, tau depletion failed to reverse memory deficits associated with APP/Aβ overproduction. On the other hand, deletion of tau alleviated the hyperlocomotion displayed by APP transgenics, suggesting that the functional effects of Aβ-tau interactions reflect the temporal appearance of these molecules in individual brain areas. |
| first_indexed | 2024-04-13T20:43:46Z |
| format | Article |
| id | doaj.art-b5ba45f74c944c0393c9dac964ffc8f1 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-04-13T20:43:46Z |
| publishDate | 2018-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-b5ba45f74c944c0393c9dac964ffc8f12022-12-22T02:30:47ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2018-03-011210.3389/fnins.2018.00124340557Tau Depletion in APP Transgenic Mice Attenuates Task-Related Hyperactivation of the Hippocampus and Differentially Influences Locomotor Activity and Spatial MemoryMisato Yoshikawa0Misato Yoshikawa1Yoshiyuki Soeda2Yoshiyuki Soeda3Makoto Michikawa4Osborne F. X. Almeida5Akihiko Takashima6Akihiko Takashima7Department of Aging Neurobiology, National Center for Geriatrics and Gerontology, Obu, JapanDepartment of Pharmacology, Shujitsu University, Okayama, JapanDepartment of Aging Neurobiology, National Center for Geriatrics and Gerontology, Obu, JapanClinical Research Center, Fukushima Medical University, Fukushima, JapanDepartment of Biochemistry, School of Medicine, Nagoya City University, Nagoya, JapanDepartment of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, GermanyDepartment of Aging Neurobiology, National Center for Geriatrics and Gerontology, Obu, JapanLaboratory for Alzheimer's Disease, Department of Life Science, Faculty of Science, Gakushuin University, Tokyo, JapanHippocampal hyperactivity, ascribed to amyloid β (Aβ)-induced imbalances in neural excitation and inhibition, is found in patients with mild cognitive impairment, a prodromal stage of Alzheimer's disease (AD). To better understand the relationship between hippocampal hyperactivity and the molecular triggers of behavioral impairments in AD, we used Mn-enhanced MRI (MEMRI) to assess neuronal activity after subjecting mice to a task requiring spatial learning and memory. Depletion of endogenous tau in an amyloid precursor protein (APP) transgenic (J20) mouse line was shown to ameliorate hippocampal hyperactivity in J20 animals, tau depletion failed to reverse memory deficits associated with APP/Aβ overproduction. On the other hand, deletion of tau alleviated the hyperlocomotion displayed by APP transgenics, suggesting that the functional effects of Aβ-tau interactions reflect the temporal appearance of these molecules in individual brain areas.http://journal.frontiersin.org/article/10.3389/fnins.2018.00124/fulltauamyloid beta-peptideshippocampushyperexcitationDementia |
| spellingShingle | Misato Yoshikawa Misato Yoshikawa Yoshiyuki Soeda Yoshiyuki Soeda Makoto Michikawa Osborne F. X. Almeida Akihiko Takashima Akihiko Takashima Tau Depletion in APP Transgenic Mice Attenuates Task-Related Hyperactivation of the Hippocampus and Differentially Influences Locomotor Activity and Spatial Memory Frontiers in Neuroscience tau amyloid beta-peptides hippocampus hyperexcitation Dementia |
| title | Tau Depletion in APP Transgenic Mice Attenuates Task-Related Hyperactivation of the Hippocampus and Differentially Influences Locomotor Activity and Spatial Memory |
| title_full | Tau Depletion in APP Transgenic Mice Attenuates Task-Related Hyperactivation of the Hippocampus and Differentially Influences Locomotor Activity and Spatial Memory |
| title_fullStr | Tau Depletion in APP Transgenic Mice Attenuates Task-Related Hyperactivation of the Hippocampus and Differentially Influences Locomotor Activity and Spatial Memory |
| title_full_unstemmed | Tau Depletion in APP Transgenic Mice Attenuates Task-Related Hyperactivation of the Hippocampus and Differentially Influences Locomotor Activity and Spatial Memory |
| title_short | Tau Depletion in APP Transgenic Mice Attenuates Task-Related Hyperactivation of the Hippocampus and Differentially Influences Locomotor Activity and Spatial Memory |
| title_sort | tau depletion in app transgenic mice attenuates task related hyperactivation of the hippocampus and differentially influences locomotor activity and spatial memory |
| topic | tau amyloid beta-peptides hippocampus hyperexcitation Dementia |
| url | http://journal.frontiersin.org/article/10.3389/fnins.2018.00124/full |
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