Quantification and correlation of amyloid-β plaque load, glial activation, GABAergic interneuron numbers, and cognitive decline in the young TgF344-AD rat model of Alzheimer’s disease
BackgroundAnimal models of Alzheimer’s disease (AD) are essential tools for investigating disease pathophysiology and conducting preclinical drug testing. In this study, we examined neuronal and glial alterations in the hippocampus and medial prefrontal cortex (mPFC) of young TgF344-AD rats and corr...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2025.1542229/full |
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| author | Anett Futácsi Anett Futácsi Anett Futácsi Kitti Rusznák Kitti Rusznák Gergely Szarka Gergely Szarka Gergely Szarka Béla Völgyi Béla Völgyi Ove Wiborg Boldizsár Czéh Boldizsár Czéh Boldizsár Czéh |
| author_facet | Anett Futácsi Anett Futácsi Anett Futácsi Kitti Rusznák Kitti Rusznák Gergely Szarka Gergely Szarka Gergely Szarka Béla Völgyi Béla Völgyi Ove Wiborg Boldizsár Czéh Boldizsár Czéh Boldizsár Czéh |
| author_sort | Anett Futácsi |
| collection | DOAJ |
| description | BackgroundAnimal models of Alzheimer’s disease (AD) are essential tools for investigating disease pathophysiology and conducting preclinical drug testing. In this study, we examined neuronal and glial alterations in the hippocampus and medial prefrontal cortex (mPFC) of young TgF344-AD rats and correlated these changes with cognitive decline and amyloid-β plaque load.MethodsWe compared TgF344-AD and non-transgenic littermate rats aged 7–8 months of age. We systematically quantified β-amyloid plaques, astrocytes, microglia, four different subtypes of GABAergic interneurons (calretinin-, cholecystokinin-, parvalbumin-, and somatostatin-positive neurons), and newly generated neurons in the hippocampus. Spatial learning and memory were assessed using the Barnes maze test.ResultsYoung TgF344-AD rats had a large number of amyloid plaques in both the hippocampus and mPFC, together with a pronounced increase in microglial cell numbers. Astrocytic activation was significant in the mPFC. Cholecystokinin-positive cell numbers were decreased in the hippocampus of transgenic rats, but calretinin-, parvalbumin-, and somatostatin-positive cell numbers were not altered. Adult neurogenesis was not affected by genotype. TgF344-AD rats had spatial learning and memory impairments, but this cognitive deficit did not correlate with amyloid plaque number or cellular changes in the brain. In the hippocampus, amyloid plaque numbers were negatively correlated with cholecystokinin-positive neuron and microglial cell numbers. In the mPFC, amyloid plaque number was negatively correlated with the number of astrocytes.ConclusionPronounced neuropathological changes were found in the hippocampus and mPFC of young TgF344-AD rats, including the loss of hippocampal cholecystokinin-positive interneurons. Some of these neuropathological changes were negatively correlated with amyloid-β plaque load, but not with cognitive impairment. |
| format | Article |
| id | doaj-art-c83ef03b816b4edc9ce91b179accbf6f |
| institution | Kabale University |
| issn | 1663-4365 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj-art-c83ef03b816b4edc9ce91b179accbf6f2025-02-12T07:25:52ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652025-02-011710.3389/fnagi.2025.15422291542229Quantification and correlation of amyloid-β plaque load, glial activation, GABAergic interneuron numbers, and cognitive decline in the young TgF344-AD rat model of Alzheimer’s diseaseAnett Futácsi0Anett Futácsi1Anett Futácsi2Kitti Rusznák3Kitti Rusznák4Gergely Szarka5Gergely Szarka6Gergely Szarka7Béla Völgyi8Béla Völgyi9Ove Wiborg10Boldizsár Czéh11Boldizsár Czéh12Boldizsár Czéh13Szentágothai Research Centre, University of Pécs, Pécs, HungaryDepartment of Laboratory Medicine, Medical School, University of Pécs, Pécs, HungaryImaging Core Facility, Szentágothai Research Centre, University of Pécs, Pécs, HungarySzentágothai Research Centre, University of Pécs, Pécs, HungaryDepartment of Laboratory Medicine, Medical School, University of Pécs, Pécs, HungarySzentágothai Research Centre, University of Pécs, Pécs, HungaryImaging Core Facility, Szentágothai Research Centre, University of Pécs, Pécs, HungaryDepartment of Neurobiology, Faculty of Sciences, University of Pécs, Pécs, HungarySzentágothai Research Centre, University of Pécs, Pécs, HungaryDepartment of Neurobiology, Faculty of Sciences, University of Pécs, Pécs, HungaryDepartment of Health Science and Technology, Aalborg University, Aalborg, DenmarkSzentágothai Research Centre, University of Pécs, Pécs, HungaryDepartment of Laboratory Medicine, Medical School, University of Pécs, Pécs, HungaryImaging Core Facility, Szentágothai Research Centre, University of Pécs, Pécs, HungaryBackgroundAnimal models of Alzheimer’s disease (AD) are essential tools for investigating disease pathophysiology and conducting preclinical drug testing. In this study, we examined neuronal and glial alterations in the hippocampus and medial prefrontal cortex (mPFC) of young TgF344-AD rats and correlated these changes with cognitive decline and amyloid-β plaque load.MethodsWe compared TgF344-AD and non-transgenic littermate rats aged 7–8 months of age. We systematically quantified β-amyloid plaques, astrocytes, microglia, four different subtypes of GABAergic interneurons (calretinin-, cholecystokinin-, parvalbumin-, and somatostatin-positive neurons), and newly generated neurons in the hippocampus. Spatial learning and memory were assessed using the Barnes maze test.ResultsYoung TgF344-AD rats had a large number of amyloid plaques in both the hippocampus and mPFC, together with a pronounced increase in microglial cell numbers. Astrocytic activation was significant in the mPFC. Cholecystokinin-positive cell numbers were decreased in the hippocampus of transgenic rats, but calretinin-, parvalbumin-, and somatostatin-positive cell numbers were not altered. Adult neurogenesis was not affected by genotype. TgF344-AD rats had spatial learning and memory impairments, but this cognitive deficit did not correlate with amyloid plaque number or cellular changes in the brain. In the hippocampus, amyloid plaque numbers were negatively correlated with cholecystokinin-positive neuron and microglial cell numbers. In the mPFC, amyloid plaque number was negatively correlated with the number of astrocytes.ConclusionPronounced neuropathological changes were found in the hippocampus and mPFC of young TgF344-AD rats, including the loss of hippocampal cholecystokinin-positive interneurons. Some of these neuropathological changes were negatively correlated with amyloid-β plaque load, but not with cognitive impairment.https://www.frontiersin.org/articles/10.3389/fnagi.2025.1542229/fullastrocyteBarnes mazecell numbercholecystokininhippocampusmicroglia |
| spellingShingle | Anett Futácsi Anett Futácsi Anett Futácsi Kitti Rusznák Kitti Rusznák Gergely Szarka Gergely Szarka Gergely Szarka Béla Völgyi Béla Völgyi Ove Wiborg Boldizsár Czéh Boldizsár Czéh Boldizsár Czéh Quantification and correlation of amyloid-β plaque load, glial activation, GABAergic interneuron numbers, and cognitive decline in the young TgF344-AD rat model of Alzheimer’s disease Frontiers in Aging Neuroscience astrocyte Barnes maze cell number cholecystokinin hippocampus microglia |
| title | Quantification and correlation of amyloid-β plaque load, glial activation, GABAergic interneuron numbers, and cognitive decline in the young TgF344-AD rat model of Alzheimer’s disease |
| title_full | Quantification and correlation of amyloid-β plaque load, glial activation, GABAergic interneuron numbers, and cognitive decline in the young TgF344-AD rat model of Alzheimer’s disease |
| title_fullStr | Quantification and correlation of amyloid-β plaque load, glial activation, GABAergic interneuron numbers, and cognitive decline in the young TgF344-AD rat model of Alzheimer’s disease |
| title_full_unstemmed | Quantification and correlation of amyloid-β plaque load, glial activation, GABAergic interneuron numbers, and cognitive decline in the young TgF344-AD rat model of Alzheimer’s disease |
| title_short | Quantification and correlation of amyloid-β plaque load, glial activation, GABAergic interneuron numbers, and cognitive decline in the young TgF344-AD rat model of Alzheimer’s disease |
| title_sort | quantification and correlation of amyloid β plaque load glial activation gabaergic interneuron numbers and cognitive decline in the young tgf344 ad rat model of alzheimer s disease |
| topic | astrocyte Barnes maze cell number cholecystokinin hippocampus microglia |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2025.1542229/full |
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