Task-dependent learning and memory deficits in the TgF344-AD rat model of Alzheimer’s disease: three key timepoints through middle-age in females
Abstract The TgF344 rat model of Alzheimer’s disease (AD) provides a comprehensive neuropathology presentation, with age-dependent development of tau tangles, amyloid-beta (A $${\beta}$$ β ) plaques, neuronal loss, and increased gliosis. The behavioral trajectory of this model, particularly relating...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-08-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-18415-1 |
| _version_ | 1828121763539582976 |
|---|---|
| author | Victoria E. Bernaud Haidyn L. Bulen Veronica L. Peña Stephanie V. Koebele Steven N. Northup-Smith Alma A. Manzo Maria Valenzuela Sanchez Zorana Opachich Ashley M. Ruhland Heather A. Bimonte-Nelson |
| author_facet | Victoria E. Bernaud Haidyn L. Bulen Veronica L. Peña Stephanie V. Koebele Steven N. Northup-Smith Alma A. Manzo Maria Valenzuela Sanchez Zorana Opachich Ashley M. Ruhland Heather A. Bimonte-Nelson |
| author_sort | Victoria E. Bernaud |
| collection | DOAJ |
| description | Abstract The TgF344 rat model of Alzheimer’s disease (AD) provides a comprehensive neuropathology presentation, with age-dependent development of tau tangles, amyloid-beta (A $${\beta}$$ β ) plaques, neuronal loss, and increased gliosis. The behavioral trajectory of this model, particularly relating to spatial learning and memory, has yet to be fully characterized. The current experiment evaluated spatial working and reference memory performance, as well as several physiological markers of health, at 3 key age points in female TgF344-AD rats: 6-months, 9-months, and 12-months. At 6 months of age, indications of working and reference memory impairments were observed in transgenic (Tg) rats on the water radial-arm maze, a complex task that requires working and reference memory simultaneously; at 12 months old, Tg impairments were observed for two working memory measures on this task. Notably, no impairments were observed at the 9-month timepoint on this maze. For the Morris maze, a measure of spatial reference memory, Tg rats demonstrated significant impairment relative to wildtype (WT) controls at all 3 age-points. Frontal cortex, entorhinal cortex, and dorsal hippocampus were evaluated for A $${\beta}$$ β 1–42 expression via western blot in Tg rats only. Analyses of A $${\beta}$$ β 1–42 expression revealed age-dependent increases in all 3 regions critical to spatial learning and memory. Measures of physiological health, including heart, uterine, and body weights, revealed unique age-specific outcomes for female Tg rats, with the 9-month timepoint identified as critical for further research within the trajectory of AD-like behavior, physiology, and pathology. |
| first_indexed | 2024-04-11T14:25:05Z |
| format | Article |
| id | doaj.art-07d713c5f02c4b568d3b1ccdd03b8d4b |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-11T14:25:05Z |
| publishDate | 2022-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-07d713c5f02c4b568d3b1ccdd03b8d4b2022-12-22T04:18:53ZengNature PortfolioScientific Reports2045-23222022-08-0112111710.1038/s41598-022-18415-1Task-dependent learning and memory deficits in the TgF344-AD rat model of Alzheimer’s disease: three key timepoints through middle-age in femalesVictoria E. Bernaud0Haidyn L. Bulen1Veronica L. Peña2Stephanie V. Koebele3Steven N. Northup-Smith4Alma A. Manzo5Maria Valenzuela Sanchez6Zorana Opachich7Ashley M. Ruhland8Heather A. Bimonte-Nelson9Behavioral Neuroscience and Comparative Psychology Division, Department of Psychology, Arizona Alzheimer’s Consortium, Arizona State UniversityBehavioral Neuroscience and Comparative Psychology Division, Department of Psychology, Arizona Alzheimer’s Consortium, Arizona State UniversityBehavioral Neuroscience and Comparative Psychology Division, Department of Psychology, Arizona Alzheimer’s Consortium, Arizona State UniversityBehavioral Neuroscience and Comparative Psychology Division, Department of Psychology, Arizona Alzheimer’s Consortium, Arizona State UniversityBehavioral Neuroscience and Comparative Psychology Division, Department of Psychology, Arizona Alzheimer’s Consortium, Arizona State UniversityBehavioral Neuroscience and Comparative Psychology Division, Department of Psychology, Arizona Alzheimer’s Consortium, Arizona State UniversityBehavioral Neuroscience and Comparative Psychology Division, Department of Psychology, Arizona Alzheimer’s Consortium, Arizona State UniversityBehavioral Neuroscience and Comparative Psychology Division, Department of Psychology, Arizona Alzheimer’s Consortium, Arizona State UniversityBehavioral Neuroscience and Comparative Psychology Division, Department of Psychology, Arizona Alzheimer’s Consortium, Arizona State UniversityBehavioral Neuroscience and Comparative Psychology Division, Department of Psychology, Arizona Alzheimer’s Consortium, Arizona State UniversityAbstract The TgF344 rat model of Alzheimer’s disease (AD) provides a comprehensive neuropathology presentation, with age-dependent development of tau tangles, amyloid-beta (A $${\beta}$$ β ) plaques, neuronal loss, and increased gliosis. The behavioral trajectory of this model, particularly relating to spatial learning and memory, has yet to be fully characterized. The current experiment evaluated spatial working and reference memory performance, as well as several physiological markers of health, at 3 key age points in female TgF344-AD rats: 6-months, 9-months, and 12-months. At 6 months of age, indications of working and reference memory impairments were observed in transgenic (Tg) rats on the water radial-arm maze, a complex task that requires working and reference memory simultaneously; at 12 months old, Tg impairments were observed for two working memory measures on this task. Notably, no impairments were observed at the 9-month timepoint on this maze. For the Morris maze, a measure of spatial reference memory, Tg rats demonstrated significant impairment relative to wildtype (WT) controls at all 3 age-points. Frontal cortex, entorhinal cortex, and dorsal hippocampus were evaluated for A $${\beta}$$ β 1–42 expression via western blot in Tg rats only. Analyses of A $${\beta}$$ β 1–42 expression revealed age-dependent increases in all 3 regions critical to spatial learning and memory. Measures of physiological health, including heart, uterine, and body weights, revealed unique age-specific outcomes for female Tg rats, with the 9-month timepoint identified as critical for further research within the trajectory of AD-like behavior, physiology, and pathology.https://doi.org/10.1038/s41598-022-18415-1 |
| spellingShingle | Victoria E. Bernaud Haidyn L. Bulen Veronica L. Peña Stephanie V. Koebele Steven N. Northup-Smith Alma A. Manzo Maria Valenzuela Sanchez Zorana Opachich Ashley M. Ruhland Heather A. Bimonte-Nelson Task-dependent learning and memory deficits in the TgF344-AD rat model of Alzheimer’s disease: three key timepoints through middle-age in females Scientific Reports |
| title | Task-dependent learning and memory deficits in the TgF344-AD rat model of Alzheimer’s disease: three key timepoints through middle-age in females |
| title_full | Task-dependent learning and memory deficits in the TgF344-AD rat model of Alzheimer’s disease: three key timepoints through middle-age in females |
| title_fullStr | Task-dependent learning and memory deficits in the TgF344-AD rat model of Alzheimer’s disease: three key timepoints through middle-age in females |
| title_full_unstemmed | Task-dependent learning and memory deficits in the TgF344-AD rat model of Alzheimer’s disease: three key timepoints through middle-age in females |
| title_short | Task-dependent learning and memory deficits in the TgF344-AD rat model of Alzheimer’s disease: three key timepoints through middle-age in females |
| title_sort | task dependent learning and memory deficits in the tgf344 ad rat model of alzheimer s disease three key timepoints through middle age in females |
| url | https://doi.org/10.1038/s41598-022-18415-1 |
| work_keys_str_mv | AT victoriaebernaud taskdependentlearningandmemorydeficitsinthetgf344adratmodelofalzheimersdiseasethreekeytimepointsthroughmiddleageinfemales AT haidynlbulen taskdependentlearningandmemorydeficitsinthetgf344adratmodelofalzheimersdiseasethreekeytimepointsthroughmiddleageinfemales AT veronicalpena taskdependentlearningandmemorydeficitsinthetgf344adratmodelofalzheimersdiseasethreekeytimepointsthroughmiddleageinfemales AT stephanievkoebele taskdependentlearningandmemorydeficitsinthetgf344adratmodelofalzheimersdiseasethreekeytimepointsthroughmiddleageinfemales AT stevennnorthupsmith taskdependentlearningandmemorydeficitsinthetgf344adratmodelofalzheimersdiseasethreekeytimepointsthroughmiddleageinfemales AT almaamanzo taskdependentlearningandmemorydeficitsinthetgf344adratmodelofalzheimersdiseasethreekeytimepointsthroughmiddleageinfemales AT mariavalenzuelasanchez taskdependentlearningandmemorydeficitsinthetgf344adratmodelofalzheimersdiseasethreekeytimepointsthroughmiddleageinfemales AT zoranaopachich taskdependentlearningandmemorydeficitsinthetgf344adratmodelofalzheimersdiseasethreekeytimepointsthroughmiddleageinfemales AT ashleymruhland taskdependentlearningandmemorydeficitsinthetgf344adratmodelofalzheimersdiseasethreekeytimepointsthroughmiddleageinfemales AT heatherabimontenelson taskdependentlearningandmemorydeficitsinthetgf344adratmodelofalzheimersdiseasethreekeytimepointsthroughmiddleageinfemales |