Mitochondrial abnormalities in a streptozotocin-induced rat model of sporadic Alzheimer's disease.

Sonia C. Correia, Renato X. Santos, Maria S. Santos, Gemma Casadesus, Joseph C. LaManna, George Perry, Mark A. Smith, Paula I. Moreira (Corresponding Author)

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

This study aimed to show that the rat model of sporadic Alzheimer’s disease (sAD) generated by the intracerebroventricular (icv) injection of a sub-diabetogenic dose of streptozotocin (icvSTZ) is characterized by brain mitochondrial abnormalities. Three-month-old male Wistar rats were investigated 5 weeks after a single bilateral icv injection of STZ (3mg/ Kg) or vehicle. icvSTZ administration induced a decrease in brain weight and cognitive decline, without affecting blood glucose levels. icvSTZ administration also resulted in a significant increase in hippocampal amyloid beta peptide 1-42 (Aβ1-42) levels as well as in cortical and hippocampal hyperphosphorylated tau protein levels. Brain mitochondria from icvSTZ rats revealed deficits in their function, as shown by a decrease in mitochondrial transmembrane potential, repolarization level, ATP content, respiratory state 3, respiratory control ratio and ADP/O index and an increase in lag phase of repolarization. Mitochondria from icvSTZ rats also displayed a decrease in pyruvate and α-ketoglutarate dehydrogenases and cytochrome c oxidase activities and an increase in the susceptibility to calcium-induced mitochondrial permeability transition. An increase in hydrogen peroxide and lipid peroxidation levels and a reduction in glutathione content were also observed in mitochondria from icvSTZ rats. These results demonstrate that the insulin-resistant brain state that characterizes this rat model of sAD is accompanied by the occurrence of mitochondrial abnormalities reinforcing the validity of this animal model to study sAD pathogenesis and potential therapies.
Original languageEnglish
Pages (from-to)406-419
Number of pages14
JournalCurrent Alzheimer Research
Volume10
Issue number4
DOIs
Publication statusPublished - May 2013

Fingerprint

Streptozocin
Alzheimer Disease
Mitochondria
Brain
tau Proteins
Injections
Electron Transport Complex IV
Pyruvic Acid
Membrane Potentials
Adenosine Diphosphate
Hydrogen Peroxide
Lipid Peroxidation
Glutathione
Blood Glucose
Wistar Rats
Permeability
Oxidoreductases
Animal Models
Adenosine Triphosphate
Insulin

Keywords

  • cortex
  • hippocampus
  • intracerebroventricular injection of streptozotocin
  • mitochondria
  • oxidative stress and damage
  • sporadic Alzheimer's disease

Cite this

Mitochondrial abnormalities in a streptozotocin-induced rat model of sporadic Alzheimer's disease. / Correia, Sonia C.; Santos, Renato X.; Santos, Maria S.; Casadesus, Gemma; LaManna, Joseph C.; Perry, George; Smith, Mark A.; Moreira, Paula I. (Corresponding Author).

In: Current Alzheimer Research, Vol. 10, No. 4, 05.2013, p. 406-419.

Research output: Contribution to journalArticle

Correia, SC, Santos, RX, Santos, MS, Casadesus, G, LaManna, JC, Perry, G, Smith, MA & Moreira, PI 2013, 'Mitochondrial abnormalities in a streptozotocin-induced rat model of sporadic Alzheimer's disease.', Current Alzheimer Research, vol. 10, no. 4, pp. 406-419. https://doi.org/10.2174/1567205011310040006
Correia, Sonia C. ; Santos, Renato X. ; Santos, Maria S. ; Casadesus, Gemma ; LaManna, Joseph C. ; Perry, George ; Smith, Mark A. ; Moreira, Paula I. / Mitochondrial abnormalities in a streptozotocin-induced rat model of sporadic Alzheimer's disease. In: Current Alzheimer Research. 2013 ; Vol. 10, No. 4. pp. 406-419.
@article{ed01d43393604057a4d6a0f81d73d455,
title = "Mitochondrial abnormalities in a streptozotocin-induced rat model of sporadic Alzheimer's disease.",
abstract = "This study aimed to show that the rat model of sporadic Alzheimer’s disease (sAD) generated by the intracerebroventricular (icv) injection of a sub-diabetogenic dose of streptozotocin (icvSTZ) is characterized by brain mitochondrial abnormalities. Three-month-old male Wistar rats were investigated 5 weeks after a single bilateral icv injection of STZ (3mg/ Kg) or vehicle. icvSTZ administration induced a decrease in brain weight and cognitive decline, without affecting blood glucose levels. icvSTZ administration also resulted in a significant increase in hippocampal amyloid beta peptide 1-42 (Aβ1-42) levels as well as in cortical and hippocampal hyperphosphorylated tau protein levels. Brain mitochondria from icvSTZ rats revealed deficits in their function, as shown by a decrease in mitochondrial transmembrane potential, repolarization level, ATP content, respiratory state 3, respiratory control ratio and ADP/O index and an increase in lag phase of repolarization. Mitochondria from icvSTZ rats also displayed a decrease in pyruvate and α-ketoglutarate dehydrogenases and cytochrome c oxidase activities and an increase in the susceptibility to calcium-induced mitochondrial permeability transition. An increase in hydrogen peroxide and lipid peroxidation levels and a reduction in glutathione content were also observed in mitochondria from icvSTZ rats. These results demonstrate that the insulin-resistant brain state that characterizes this rat model of sAD is accompanied by the occurrence of mitochondrial abnormalities reinforcing the validity of this animal model to study sAD pathogenesis and potential therapies.",
keywords = "cortex, hippocampus, intracerebroventricular injection of streptozotocin, mitochondria, oxidative stress and damage, sporadic Alzheimer's disease",
author = "Correia, {Sonia C.} and Santos, {Renato X.} and Santos, {Maria S.} and Gemma Casadesus and LaManna, {Joseph C.} and George Perry and Smith, {Mark A.} and Moreira, {Paula I.}",
year = "2013",
month = "5",
doi = "10.2174/1567205011310040006",
language = "English",
volume = "10",
pages = "406--419",
journal = "Current Alzheimer Research",
issn = "1567-2050",
publisher = "Bentham Science Publishers B.V.",
number = "4",

}

TY - JOUR

T1 - Mitochondrial abnormalities in a streptozotocin-induced rat model of sporadic Alzheimer's disease.

AU - Correia, Sonia C.

AU - Santos, Renato X.

AU - Santos, Maria S.

AU - Casadesus, Gemma

AU - LaManna, Joseph C.

AU - Perry, George

AU - Smith, Mark A.

AU - Moreira, Paula I.

PY - 2013/5

Y1 - 2013/5

N2 - This study aimed to show that the rat model of sporadic Alzheimer’s disease (sAD) generated by the intracerebroventricular (icv) injection of a sub-diabetogenic dose of streptozotocin (icvSTZ) is characterized by brain mitochondrial abnormalities. Three-month-old male Wistar rats were investigated 5 weeks after a single bilateral icv injection of STZ (3mg/ Kg) or vehicle. icvSTZ administration induced a decrease in brain weight and cognitive decline, without affecting blood glucose levels. icvSTZ administration also resulted in a significant increase in hippocampal amyloid beta peptide 1-42 (Aβ1-42) levels as well as in cortical and hippocampal hyperphosphorylated tau protein levels. Brain mitochondria from icvSTZ rats revealed deficits in their function, as shown by a decrease in mitochondrial transmembrane potential, repolarization level, ATP content, respiratory state 3, respiratory control ratio and ADP/O index and an increase in lag phase of repolarization. Mitochondria from icvSTZ rats also displayed a decrease in pyruvate and α-ketoglutarate dehydrogenases and cytochrome c oxidase activities and an increase in the susceptibility to calcium-induced mitochondrial permeability transition. An increase in hydrogen peroxide and lipid peroxidation levels and a reduction in glutathione content were also observed in mitochondria from icvSTZ rats. These results demonstrate that the insulin-resistant brain state that characterizes this rat model of sAD is accompanied by the occurrence of mitochondrial abnormalities reinforcing the validity of this animal model to study sAD pathogenesis and potential therapies.

AB - This study aimed to show that the rat model of sporadic Alzheimer’s disease (sAD) generated by the intracerebroventricular (icv) injection of a sub-diabetogenic dose of streptozotocin (icvSTZ) is characterized by brain mitochondrial abnormalities. Three-month-old male Wistar rats were investigated 5 weeks after a single bilateral icv injection of STZ (3mg/ Kg) or vehicle. icvSTZ administration induced a decrease in brain weight and cognitive decline, without affecting blood glucose levels. icvSTZ administration also resulted in a significant increase in hippocampal amyloid beta peptide 1-42 (Aβ1-42) levels as well as in cortical and hippocampal hyperphosphorylated tau protein levels. Brain mitochondria from icvSTZ rats revealed deficits in their function, as shown by a decrease in mitochondrial transmembrane potential, repolarization level, ATP content, respiratory state 3, respiratory control ratio and ADP/O index and an increase in lag phase of repolarization. Mitochondria from icvSTZ rats also displayed a decrease in pyruvate and α-ketoglutarate dehydrogenases and cytochrome c oxidase activities and an increase in the susceptibility to calcium-induced mitochondrial permeability transition. An increase in hydrogen peroxide and lipid peroxidation levels and a reduction in glutathione content were also observed in mitochondria from icvSTZ rats. These results demonstrate that the insulin-resistant brain state that characterizes this rat model of sAD is accompanied by the occurrence of mitochondrial abnormalities reinforcing the validity of this animal model to study sAD pathogenesis and potential therapies.

KW - cortex

KW - hippocampus

KW - intracerebroventricular injection of streptozotocin

KW - mitochondria

KW - oxidative stress and damage

KW - sporadic Alzheimer's disease

UR - http://europepmc.org/abstract/med/23061885

U2 - 10.2174/1567205011310040006

DO - 10.2174/1567205011310040006

M3 - Article

C2 - 23061885

VL - 10

SP - 406

EP - 419

JO - Current Alzheimer Research

JF - Current Alzheimer Research

SN - 1567-2050

IS - 4

ER -