Selective Regional Loss of Cortical Synapses Lacking Presynaptic Mitochondria in the 5xFAD Mouse Model
Synaptic loss in Alzheimer's disease (AD) is strongly correlated with cognitive impairment. Accumulating evidence indicates that amyloid pathology leads to synaptic degeneration and mitochondrial damage in AD. However, it remains unclear whether synapses and presynaptic mitochondria are differe...
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Neuroanatomy |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnana.2021.690168/full |
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| author | Na-young Seo Na-young Seo Gyu Hyun Kim Jeong Eun Noh Ji Won Shin Chan Hee Lee Kea Joo Lee Kea Joo Lee |
| author_facet | Na-young Seo Na-young Seo Gyu Hyun Kim Jeong Eun Noh Ji Won Shin Chan Hee Lee Kea Joo Lee Kea Joo Lee |
| author_sort | Na-young Seo |
| collection | DOAJ |
| description | Synaptic loss in Alzheimer's disease (AD) is strongly correlated with cognitive impairment. Accumulating evidence indicates that amyloid pathology leads to synaptic degeneration and mitochondrial damage in AD. However, it remains unclear whether synapses and presynaptic mitochondria are differentially affected in various cortical regions of the AD brain at the ultrastructural level. Using serial block-face scanning electron microscopy, we assessed synaptic structures in the medial prefrontal cortex (mPFC) and primary visual cortex (V1) of the 5xFAD mouse model of AD. At 6 months of age, 5xFAD mice exhibited significantly elevated levels of amyloid deposition in layer 2/3 of the mPFC but not V1. Accordingly, three-dimensional reconstruction of synaptic connectivity revealed a significant reduction in excitatory synaptic density in layer 2 of the mPFC, but not V1, of male transgenic mice. Notably, the density of synapses lacking presynaptic mitochondria was selectively decreased in the mPFC of 5xFAD mice, with no change in the density of mitochondria-containing synapses. Further classification of spines into shape categories confirmed a preferential loss of thin spines whose presynaptic boutons were largely devoid of mitochondria in the 5xFAD mPFC. Furthermore, the number of mitochondria per bouton in spared mitochondria-containing boutons was reduced in the mPFC, but not V1, of 5xFAD mice. Collectively, these results highlight region-specific vulnerability of cortical synapses to amyloid deposition and suggest that the presence of presynaptic mitochondria may affect synaptic degeneration in AD. |
| first_indexed | 2024-12-19T06:32:01Z |
| format | Article |
| id | doaj.art-734721b0f5474ee88096a53142353c98 |
| institution | Directory Open Access Journal |
| issn | 1662-5129 |
| language | English |
| last_indexed | 2024-12-19T06:32:01Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroanatomy |
| spelling | doaj.art-734721b0f5474ee88096a53142353c982022-12-21T20:32:21ZengFrontiers Media S.A.Frontiers in Neuroanatomy1662-51292021-06-011510.3389/fnana.2021.690168690168Selective Regional Loss of Cortical Synapses Lacking Presynaptic Mitochondria in the 5xFAD Mouse ModelNa-young Seo0Na-young Seo1Gyu Hyun Kim2Jeong Eun Noh3Ji Won Shin4Chan Hee Lee5Kea Joo Lee6Kea Joo Lee7Neural Circuits Research Group, Korea Brain Research Institute, Daegu, South KoreaDepartment of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology, Daegu, South KoreaNeural Circuits Research Group, Korea Brain Research Institute, Daegu, South KoreaNeural Circuits Research Group, Korea Brain Research Institute, Daegu, South KoreaNeural Circuits Research Group, Korea Brain Research Institute, Daegu, South KoreaNeural Circuits Research Group, Korea Brain Research Institute, Daegu, South KoreaNeural Circuits Research Group, Korea Brain Research Institute, Daegu, South KoreaDepartment of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology, Daegu, South KoreaSynaptic loss in Alzheimer's disease (AD) is strongly correlated with cognitive impairment. Accumulating evidence indicates that amyloid pathology leads to synaptic degeneration and mitochondrial damage in AD. However, it remains unclear whether synapses and presynaptic mitochondria are differentially affected in various cortical regions of the AD brain at the ultrastructural level. Using serial block-face scanning electron microscopy, we assessed synaptic structures in the medial prefrontal cortex (mPFC) and primary visual cortex (V1) of the 5xFAD mouse model of AD. At 6 months of age, 5xFAD mice exhibited significantly elevated levels of amyloid deposition in layer 2/3 of the mPFC but not V1. Accordingly, three-dimensional reconstruction of synaptic connectivity revealed a significant reduction in excitatory synaptic density in layer 2 of the mPFC, but not V1, of male transgenic mice. Notably, the density of synapses lacking presynaptic mitochondria was selectively decreased in the mPFC of 5xFAD mice, with no change in the density of mitochondria-containing synapses. Further classification of spines into shape categories confirmed a preferential loss of thin spines whose presynaptic boutons were largely devoid of mitochondria in the 5xFAD mPFC. Furthermore, the number of mitochondria per bouton in spared mitochondria-containing boutons was reduced in the mPFC, but not V1, of 5xFAD mice. Collectively, these results highlight region-specific vulnerability of cortical synapses to amyloid deposition and suggest that the presence of presynaptic mitochondria may affect synaptic degeneration in AD.https://www.frontiersin.org/articles/10.3389/fnana.2021.690168/fullAlzheimer's disease5xFADsynapsemitochondriacortexelectron microscopy |
| spellingShingle | Na-young Seo Na-young Seo Gyu Hyun Kim Jeong Eun Noh Ji Won Shin Chan Hee Lee Kea Joo Lee Kea Joo Lee Selective Regional Loss of Cortical Synapses Lacking Presynaptic Mitochondria in the 5xFAD Mouse Model Frontiers in Neuroanatomy Alzheimer's disease 5xFAD synapse mitochondria cortex electron microscopy |
| title | Selective Regional Loss of Cortical Synapses Lacking Presynaptic Mitochondria in the 5xFAD Mouse Model |
| title_full | Selective Regional Loss of Cortical Synapses Lacking Presynaptic Mitochondria in the 5xFAD Mouse Model |
| title_fullStr | Selective Regional Loss of Cortical Synapses Lacking Presynaptic Mitochondria in the 5xFAD Mouse Model |
| title_full_unstemmed | Selective Regional Loss of Cortical Synapses Lacking Presynaptic Mitochondria in the 5xFAD Mouse Model |
| title_short | Selective Regional Loss of Cortical Synapses Lacking Presynaptic Mitochondria in the 5xFAD Mouse Model |
| title_sort | selective regional loss of cortical synapses lacking presynaptic mitochondria in the 5xfad mouse model |
| topic | Alzheimer's disease 5xFAD synapse mitochondria cortex electron microscopy |
| url | https://www.frontiersin.org/articles/10.3389/fnana.2021.690168/full |
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