Type 2 diabetic and Alzheimer's disease mice present similar behavioral, cognitive, and vascular anomalies.

Cristina Carvalho; Nuno Machado; Paula C. Mota; Sónia C. Correia; Susana Cardoso; Renato X. Santos; Maria S. Santos; Catarina R. Oliveira; Paula I. Moreira

doi:10.3233/JAD-130005

Type 2 diabetic and Alzheimer's disease mice present similar behavioral, cognitive, and vascular anomalies.

Cristina Carvalho, Nuno Machado, Paula C. Mota, Sónia C. Correia, Susana Cardoso, Renato X. Santos, Maria S. Santos, Catarina R. Oliveira, Paula I. Moreira (Corresponding Author)

University of Coimbra

Research output: Contribution to journal › Article › peer-review

69 Citations (Scopus)

Abstract

Type 2 diabetes (T2D) is considered a major risk factor for Alzheimer's disease (AD). To elucidate the links between both pathological conditions, we compared behavioral and cognitive functions, cerebral amyloid-β peptide (Aβ) levels and vasculature integrity of 11-month-old T2D and AD mice. For this purpose, we performed behavioral tests (open field, object recognition, Y-maze, and elevated plus maze tests), ELISA to assess plasma markers of endothelial/vascular dysfunction, spectrophotometric assays to evaluate cerebral vascular permeability and enzymatic activities, and immunohistochemistry for the assessment of Aβ levels. Both T2D and AD showed similar behavioral and cognitive anomalies characterized by increased fear and anxiety and decreased learning and memory abilities. Interestingly, both groups of animals presented increased plasma markers of endothelial/vascular dysfunction and permeability of cerebral vasculature and impaired mitochondrial enzymatic activities. In addition, a significant increase in Aβ levels was observed in the cortex and hippocampus of T2D mice. These results support the notion that T2D predisposes to cerebrovascular alterations, cognitive decline, and development of AD.

Original language	English
Pages (from-to)	623-635
Number of pages	13
Journal	Journal of Alzheimer's Disease
Volume	35
Issue number	3
DOIs	https://doi.org/10.3233/JAD-130005
Publication status	Published - 6 May 2013
Externally published	Yes

Bibliographical note

The authors’ work is supported by the Fundacao para a Ciencia e aTecnologia co-funded by Fundo Europeu para o Desenvolvimento Regional (PTDC/SAUNEU/103325/2008) via Programa Operacional Factores de Competitividade, and Quadro de Referencia Estrategico Nacional (QREN DO-IT). C.C. has a PhD fellowship from FCT (SFRH/BD/43965/2008).
We thank Dr. Rodrigo Cunha and Dr. Joao Ramalho Santos from the Center for Neuroscience and Cell Biology, University of Coimbra, for their support with behavioral and microscopy studies.
We also thank Drs. Cristina Sena and Rosa Fernandes, from the Faculty of Medicine, University of Coimbra, for their help with Evans blue assay.
Authors’ disclosures available online http://www.jalz.com/disclosures/view.php?id=1677).

Keywords

Alzheimer's disease
brain vasculature
behavior and cognitive function
mitochondria
type 2 diabetes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Type 2 diabetic and Alzheimer's disease mice present similar behavioral, cognitive, and vascular anomalies.",

abstract = "Type 2 diabetes (T2D) is considered a major risk factor for Alzheimer's disease (AD). To elucidate the links between both pathological conditions, we compared behavioral and cognitive functions, cerebral amyloid-β peptide (Aβ) levels and vasculature integrity of 11-month-old T2D and AD mice. For this purpose, we performed behavioral tests (open field, object recognition, Y-maze, and elevated plus maze tests), ELISA to assess plasma markers of endothelial/vascular dysfunction, spectrophotometric assays to evaluate cerebral vascular permeability and enzymatic activities, and immunohistochemistry for the assessment of Aβ levels. Both T2D and AD showed similar behavioral and cognitive anomalies characterized by increased fear and anxiety and decreased learning and memory abilities. Interestingly, both groups of animals presented increased plasma markers of endothelial/vascular dysfunction and permeability of cerebral vasculature and impaired mitochondrial enzymatic activities. In addition, a significant increase in Aβ levels was observed in the cortex and hippocampus of T2D mice. These results support the notion that T2D predisposes to cerebrovascular alterations, cognitive decline, and development of AD.",

keywords = "Alzheimer's disease, brain vasculature, behavior and cognitive function, mitochondria, type 2 diabetes",

author = "Cristina Carvalho and Nuno Machado and Mota, {Paula C.} and Correia, {S{\'o}nia C.} and Susana Cardoso and Santos, {Renato X.} and Santos, {Maria S.} and Oliveira, {Catarina R.} and Moreira, {Paula I.}",

note = "The authors{\textquoteright} work is supported by the Fundacao para a Ciencia e aTecnologia co-funded by Fundo Europeu para o Desenvolvimento Regional (PTDC/SAUNEU/103325/2008) via Programa Operacional Factores de Competitividade, and Quadro de Referencia Estrategico Nacional (QREN DO-IT). C.C. has a PhD fellowship from FCT (SFRH/BD/43965/2008). We thank Dr. Rodrigo Cunha and Dr. Joao Ramalho Santos from the Center for Neuroscience and Cell Biology, University of Coimbra, for their support with behavioral and microscopy studies. We also thank Drs. Cristina Sena and Rosa Fernandes, from the Faculty of Medicine, University of Coimbra, for their help with Evans blue assay. Authors{\textquoteright} disclosures available online http://www.jalz.com/disclosures/view.php?id=1677).",

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doi = "10.3233/JAD-130005",

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T1 - Type 2 diabetic and Alzheimer's disease mice present similar behavioral, cognitive, and vascular anomalies.

AU - Carvalho, Cristina

AU - Machado, Nuno

AU - Mota, Paula C.

AU - Correia, Sónia C.

AU - Cardoso, Susana

AU - Santos, Renato X.

AU - Santos, Maria S.

AU - Oliveira, Catarina R.

AU - Moreira, Paula I.

N1 - The authors’ work is supported by the Fundacao para a Ciencia e aTecnologia co-funded by Fundo Europeu para o Desenvolvimento Regional (PTDC/SAUNEU/103325/2008) via Programa Operacional Factores de Competitividade, and Quadro de Referencia Estrategico Nacional (QREN DO-IT). C.C. has a PhD fellowship from FCT (SFRH/BD/43965/2008). We thank Dr. Rodrigo Cunha and Dr. Joao Ramalho Santos from the Center for Neuroscience and Cell Biology, University of Coimbra, for their support with behavioral and microscopy studies. We also thank Drs. Cristina Sena and Rosa Fernandes, from the Faculty of Medicine, University of Coimbra, for their help with Evans blue assay. Authors’ disclosures available online http://www.jalz.com/disclosures/view.php?id=1677).

PY - 2013/5/6

Y1 - 2013/5/6

N2 - Type 2 diabetes (T2D) is considered a major risk factor for Alzheimer's disease (AD). To elucidate the links between both pathological conditions, we compared behavioral and cognitive functions, cerebral amyloid-β peptide (Aβ) levels and vasculature integrity of 11-month-old T2D and AD mice. For this purpose, we performed behavioral tests (open field, object recognition, Y-maze, and elevated plus maze tests), ELISA to assess plasma markers of endothelial/vascular dysfunction, spectrophotometric assays to evaluate cerebral vascular permeability and enzymatic activities, and immunohistochemistry for the assessment of Aβ levels. Both T2D and AD showed similar behavioral and cognitive anomalies characterized by increased fear and anxiety and decreased learning and memory abilities. Interestingly, both groups of animals presented increased plasma markers of endothelial/vascular dysfunction and permeability of cerebral vasculature and impaired mitochondrial enzymatic activities. In addition, a significant increase in Aβ levels was observed in the cortex and hippocampus of T2D mice. These results support the notion that T2D predisposes to cerebrovascular alterations, cognitive decline, and development of AD.

AB - Type 2 diabetes (T2D) is considered a major risk factor for Alzheimer's disease (AD). To elucidate the links between both pathological conditions, we compared behavioral and cognitive functions, cerebral amyloid-β peptide (Aβ) levels and vasculature integrity of 11-month-old T2D and AD mice. For this purpose, we performed behavioral tests (open field, object recognition, Y-maze, and elevated plus maze tests), ELISA to assess plasma markers of endothelial/vascular dysfunction, spectrophotometric assays to evaluate cerebral vascular permeability and enzymatic activities, and immunohistochemistry for the assessment of Aβ levels. Both T2D and AD showed similar behavioral and cognitive anomalies characterized by increased fear and anxiety and decreased learning and memory abilities. Interestingly, both groups of animals presented increased plasma markers of endothelial/vascular dysfunction and permeability of cerebral vasculature and impaired mitochondrial enzymatic activities. In addition, a significant increase in Aβ levels was observed in the cortex and hippocampus of T2D mice. These results support the notion that T2D predisposes to cerebrovascular alterations, cognitive decline, and development of AD.

KW - Alzheimer's disease

KW - brain vasculature

KW - behavior and cognitive function

KW - mitochondria

KW - type 2 diabetes

UR - http://europepmc.org/abstract/med/23478310

U2 - 10.3233/JAD-130005

DO - 10.3233/JAD-130005

M3 - Article

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SN - 1387-2877

VL - 35

SP - 623

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JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

IS - 3

ER -

Type 2 diabetic and Alzheimer's disease mice present similar behavioral, cognitive, and vascular anomalies.

Abstract

Bibliographical note

Keywords

UN SDGs

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