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Impaired structural correlates of memory in Alzheimer's disease mice.

Badhwar A, Lerch JP, Hamel E, Sled JG - Neuroimage Clin (2013)

Bottom Line: The healthy adult brain demonstrates robust learning-induced neuroanatomical plasticity.Using high-resolution post-mortem MRI and deformation-based morphometry, we demonstrate spatial learning and memory-induced focal volume increase in the hippocampus of wild-type mice, an effect that was severely attenuated in APP mice, consistent with their unsuccessful performance in the spatial Morris water maze.Pioglitazone-treatment in APP mice completely rescued functional hyperemia and exerted beneficial effects on spatial learning and memory-recall, but it did not improve hippocampal plasticity.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cerebrovascular Research, Montreal Neurological Institute, McGill University, Montréal, QC H3A 2B4, Canada.

ABSTRACT
The healthy adult brain demonstrates robust learning-induced neuroanatomical plasticity. While altered neuroanatomical plasticity is suspected to be a factor mitigating the progressive cognitive decline in Alzheimer's disease (AD), it is not known to what extent this plasticity is affected by AD. We evaluated whether spatial learning and memory-induced neuroanatomical plasticity are diminished in an adult mouse model of AD (APP mice) featuring amyloid beta-driven cognitive and cerebrovascular dysfunction. We also evaluated the effect of early, long-term pioglitazone-treatment on functional hyperemia, spatial learning and memory, and associated neuroanatomical plasticity. Using high-resolution post-mortem MRI and deformation-based morphometry, we demonstrate spatial learning and memory-induced focal volume increase in the hippocampus of wild-type mice, an effect that was severely attenuated in APP mice, consistent with their unsuccessful performance in the spatial Morris water maze. These findings implicate impaired neuroanatomical plasticity as an important contributing factor to cognitive deficits in the APP mouse model of AD. Pioglitazone-treatment in APP mice completely rescued functional hyperemia and exerted beneficial effects on spatial learning and memory-recall, but it did not improve hippocampal plasticity.

No MeSH data available.


Related in: MedlinePlus

Pioglitazone did not reduce Aβ plaque load in the hippocampus. Qualitatively, the area occupied by thioflavin S-stained mature, dense-core amyloid plaques in the hippocampus of 6-month-old (A) APP mice and (B) pioglitazone-treated APP (APP (pio)) mice were comparable. (C) Quantitatively, pioglitazone-treatment did not reduce amyloid plaque load. Scale bar: 1 mm (4 × zoom), error bars: SEM, pio: pioglitazone.
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f0035: Pioglitazone did not reduce Aβ plaque load in the hippocampus. Qualitatively, the area occupied by thioflavin S-stained mature, dense-core amyloid plaques in the hippocampus of 6-month-old (A) APP mice and (B) pioglitazone-treated APP (APP (pio)) mice were comparable. (C) Quantitatively, pioglitazone-treatment did not reduce amyloid plaque load. Scale bar: 1 mm (4 × zoom), error bars: SEM, pio: pioglitazone.

Mentions: No significant differences in the volume of brain structures or cortical thickness were detected in pioglitazone-treated APP and WT mice compared to their respective untreated controls. In line with the overall lack of treatment-effect on brain structure volumes, Nissl-staining did not detect any qualitative (Fig. 5A, D) nor significant quantitative (Fig. 5B, C, E, F) differences in the hippocampal CA1 subfield between pioglitazone-treated APP and WT mice compared to their respective untreated controls. Moreover, consistent with no treatment effect on brain volume and with earlier findings in old APP mice (Nicolakakis et al., 2008), there was also no difference in the Aβ plaque load in the hippocampus between pioglitazone-treated and untreated APP mice (Fig. 7).


Impaired structural correlates of memory in Alzheimer's disease mice.

Badhwar A, Lerch JP, Hamel E, Sled JG - Neuroimage Clin (2013)

Pioglitazone did not reduce Aβ plaque load in the hippocampus. Qualitatively, the area occupied by thioflavin S-stained mature, dense-core amyloid plaques in the hippocampus of 6-month-old (A) APP mice and (B) pioglitazone-treated APP (APP (pio)) mice were comparable. (C) Quantitatively, pioglitazone-treatment did not reduce amyloid plaque load. Scale bar: 1 mm (4 × zoom), error bars: SEM, pio: pioglitazone.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814975&req=5

f0035: Pioglitazone did not reduce Aβ plaque load in the hippocampus. Qualitatively, the area occupied by thioflavin S-stained mature, dense-core amyloid plaques in the hippocampus of 6-month-old (A) APP mice and (B) pioglitazone-treated APP (APP (pio)) mice were comparable. (C) Quantitatively, pioglitazone-treatment did not reduce amyloid plaque load. Scale bar: 1 mm (4 × zoom), error bars: SEM, pio: pioglitazone.
Mentions: No significant differences in the volume of brain structures or cortical thickness were detected in pioglitazone-treated APP and WT mice compared to their respective untreated controls. In line with the overall lack of treatment-effect on brain structure volumes, Nissl-staining did not detect any qualitative (Fig. 5A, D) nor significant quantitative (Fig. 5B, C, E, F) differences in the hippocampal CA1 subfield between pioglitazone-treated APP and WT mice compared to their respective untreated controls. Moreover, consistent with no treatment effect on brain volume and with earlier findings in old APP mice (Nicolakakis et al., 2008), there was also no difference in the Aβ plaque load in the hippocampus between pioglitazone-treated and untreated APP mice (Fig. 7).

Bottom Line: The healthy adult brain demonstrates robust learning-induced neuroanatomical plasticity.Using high-resolution post-mortem MRI and deformation-based morphometry, we demonstrate spatial learning and memory-induced focal volume increase in the hippocampus of wild-type mice, an effect that was severely attenuated in APP mice, consistent with their unsuccessful performance in the spatial Morris water maze.Pioglitazone-treatment in APP mice completely rescued functional hyperemia and exerted beneficial effects on spatial learning and memory-recall, but it did not improve hippocampal plasticity.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cerebrovascular Research, Montreal Neurological Institute, McGill University, Montréal, QC H3A 2B4, Canada.

ABSTRACT
The healthy adult brain demonstrates robust learning-induced neuroanatomical plasticity. While altered neuroanatomical plasticity is suspected to be a factor mitigating the progressive cognitive decline in Alzheimer's disease (AD), it is not known to what extent this plasticity is affected by AD. We evaluated whether spatial learning and memory-induced neuroanatomical plasticity are diminished in an adult mouse model of AD (APP mice) featuring amyloid beta-driven cognitive and cerebrovascular dysfunction. We also evaluated the effect of early, long-term pioglitazone-treatment on functional hyperemia, spatial learning and memory, and associated neuroanatomical plasticity. Using high-resolution post-mortem MRI and deformation-based morphometry, we demonstrate spatial learning and memory-induced focal volume increase in the hippocampus of wild-type mice, an effect that was severely attenuated in APP mice, consistent with their unsuccessful performance in the spatial Morris water maze. These findings implicate impaired neuroanatomical plasticity as an important contributing factor to cognitive deficits in the APP mouse model of AD. Pioglitazone-treatment in APP mice completely rescued functional hyperemia and exerted beneficial effects on spatial learning and memory-recall, but it did not improve hippocampal plasticity.

No MeSH data available.


Related in: MedlinePlus