Longitudinal analysis of the behavioral phenotype in a novel transgenic rat model of early stages of Alzheimer’s disease
Intraneuronal accumulation of amyloid β (iAβ) has been linked to mild cognitive impairment that may precede Alzheimer’s disease (AD) onset. This neuropathological trait was recently mimicked in a novel animal model of AD, the hemizygous transgenic McGill-R-Thy1-APP (Tg+/-) rat. The characterization...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-09-01
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| Series: | Frontiers in Behavioral Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnbeh.2014.00321/full |
| _version_ | 1818057746274058240 |
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| author | Pablo eGaleano Pablo eGaleano Pamela V. Martino Adami Sonia eDo Carmo Eduardo eBlanco Cecilia eRotondaro Francisco eCapani Eduardo Miguel Castaño A. Claudio Cuello Laura eMorelli |
| author_facet | Pablo eGaleano Pablo eGaleano Pamela V. Martino Adami Sonia eDo Carmo Eduardo eBlanco Cecilia eRotondaro Francisco eCapani Eduardo Miguel Castaño A. Claudio Cuello Laura eMorelli |
| author_sort | Pablo eGaleano |
| collection | DOAJ |
| description | Intraneuronal accumulation of amyloid β (iAβ) has been linked to mild cognitive impairment that may precede Alzheimer’s disease (AD) onset. This neuropathological trait was recently mimicked in a novel animal model of AD, the hemizygous transgenic McGill-R-Thy1-APP (Tg+/-) rat. The characterization of the behavioral phenotypes in this animal model could provide a baseline of efficacy for earlier therapeutic interventions. The aim of the present study was to undertake a longitudinal study of Aβ accumulation and a comprehensive behavioral evaluation of this transgenic rat model. We assessed exploratory activity, anxiety-related behaviors, recognition memory, working memory, spatial learning and reference memory at 3, 6 and 12 months of age. In parallel, we measured Aβ by ELISA, Western blots and semiquantitative immunohistochemistry in hippocampal samples. SDS-soluble Aβ peptide accumulated at low levels (~9 pg/mg) without differences among ages. However, Western blots showed SDS-resistant Aβ oligomers (~30 kDa) at 6 and 12 months, but not at 3 months. When compared to wild-type (WT), male Tg+/- rats exhibited a spatial reference memory deficit in the Morris Water Maze (MWM) as early as 3 months of age, which persisted at 6 and 12 months. In addition, Tg+/- rats displayed a working memory impairment in the Y-maze and higher anxiety levels in the Open Field (OF) at 6 and 12 months of age, but not at 3 months. Exploratory activity in the OF was similar to that of WT at all time points. Spatial learning in the MWM and the recognition memory, as assessed by the Novel Object Recognition Test, were unimpaired at any time point. The data from the present study demonstrate that the hemizygous transgenic McGill-R-Thy1-APP rat has a wide array of behavioral and cognitive impairments from young adulthood to middle-age. The low Aβ burden and early emotional and cognitive deficits in this transgenic rat model supports its potential use for drug discovery purposes in early AD. |
| first_indexed | 2024-12-10T12:49:38Z |
| format | Article |
| id | doaj.art-fb57b5ac85714be989d0a74443b51b86 |
| institution | Directory Open Access Journal |
| issn | 1662-5153 |
| language | English |
| last_indexed | 2024-12-10T12:49:38Z |
| publishDate | 2014-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Behavioral Neuroscience |
| spelling | doaj.art-fb57b5ac85714be989d0a74443b51b862022-12-22T01:48:18ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532014-09-01810.3389/fnbeh.2014.00321103977Longitudinal analysis of the behavioral phenotype in a novel transgenic rat model of early stages of Alzheimer’s diseasePablo eGaleano0Pablo eGaleano1Pamela V. Martino Adami2Sonia eDo Carmo3Eduardo eBlanco4Cecilia eRotondaro5Francisco eCapani6Eduardo Miguel Castaño7A. Claudio Cuello8Laura eMorelli9Fundación Instituto Leloir-IIBBA (CONICET)Instituto de Investigaciones Cardiológicas Prof. Dr. Alberto C. Taquini (ININCA), UBA-CONICETFundación Instituto Leloir-IIBBA (CONICET)McGill UniversityUniversitat de LleidaFundación Instituto LeloirInstituto de Investigaciones Cardiológicas Prof. Dr. Alberto C. Taquini (ININCA), UBA-CONICETFundación Instituto Leloir-IIBBA (CONICET)McGill UniversityFundación Instituto Leloir-IIBBA (CONICET)Intraneuronal accumulation of amyloid β (iAβ) has been linked to mild cognitive impairment that may precede Alzheimer’s disease (AD) onset. This neuropathological trait was recently mimicked in a novel animal model of AD, the hemizygous transgenic McGill-R-Thy1-APP (Tg+/-) rat. The characterization of the behavioral phenotypes in this animal model could provide a baseline of efficacy for earlier therapeutic interventions. The aim of the present study was to undertake a longitudinal study of Aβ accumulation and a comprehensive behavioral evaluation of this transgenic rat model. We assessed exploratory activity, anxiety-related behaviors, recognition memory, working memory, spatial learning and reference memory at 3, 6 and 12 months of age. In parallel, we measured Aβ by ELISA, Western blots and semiquantitative immunohistochemistry in hippocampal samples. SDS-soluble Aβ peptide accumulated at low levels (~9 pg/mg) without differences among ages. However, Western blots showed SDS-resistant Aβ oligomers (~30 kDa) at 6 and 12 months, but not at 3 months. When compared to wild-type (WT), male Tg+/- rats exhibited a spatial reference memory deficit in the Morris Water Maze (MWM) as early as 3 months of age, which persisted at 6 and 12 months. In addition, Tg+/- rats displayed a working memory impairment in the Y-maze and higher anxiety levels in the Open Field (OF) at 6 and 12 months of age, but not at 3 months. Exploratory activity in the OF was similar to that of WT at all time points. Spatial learning in the MWM and the recognition memory, as assessed by the Novel Object Recognition Test, were unimpaired at any time point. The data from the present study demonstrate that the hemizygous transgenic McGill-R-Thy1-APP rat has a wide array of behavioral and cognitive impairments from young adulthood to middle-age. The low Aβ burden and early emotional and cognitive deficits in this transgenic rat model supports its potential use for drug discovery purposes in early AD.http://journal.frontiersin.org/Journal/10.3389/fnbeh.2014.00321/fullAnxietyAlzheimer’s diseasecognitive impairmentamyloid βtransgenic rat models |
| spellingShingle | Pablo eGaleano Pablo eGaleano Pamela V. Martino Adami Sonia eDo Carmo Eduardo eBlanco Cecilia eRotondaro Francisco eCapani Eduardo Miguel Castaño A. Claudio Cuello Laura eMorelli Longitudinal analysis of the behavioral phenotype in a novel transgenic rat model of early stages of Alzheimer’s disease Frontiers in Behavioral Neuroscience Anxiety Alzheimer’s disease cognitive impairment amyloid β transgenic rat models |
| title | Longitudinal analysis of the behavioral phenotype in a novel transgenic rat model of early stages of Alzheimer’s disease |
| title_full | Longitudinal analysis of the behavioral phenotype in a novel transgenic rat model of early stages of Alzheimer’s disease |
| title_fullStr | Longitudinal analysis of the behavioral phenotype in a novel transgenic rat model of early stages of Alzheimer’s disease |
| title_full_unstemmed | Longitudinal analysis of the behavioral phenotype in a novel transgenic rat model of early stages of Alzheimer’s disease |
| title_short | Longitudinal analysis of the behavioral phenotype in a novel transgenic rat model of early stages of Alzheimer’s disease |
| title_sort | longitudinal analysis of the behavioral phenotype in a novel transgenic rat model of early stages of alzheimer s disease |
| topic | Anxiety Alzheimer’s disease cognitive impairment amyloid β transgenic rat models |
| url | http://journal.frontiersin.org/Journal/10.3389/fnbeh.2014.00321/full |
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