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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

Alterations in midline-adjacent CA1 area of the hippocampus in APP mice. (A) Nissl-stained hippocampal sections reveal disorganization of cells in the midline-adjacent CA1 pyramidal layer in 6-month-old APP mice. (B) Compared to age matched control () and pioglitazone-treated () WT mice, the area occupied by cell bodies is significantly reduced in control () and pioglitazone-treated () APP mice. (C) Similarly, irrespective of pioglitazone-treatment status, the average number of cells is significantly lower in APP mice compared to WT mice. (D) No qualitative difference was observed in the lateral CA1 region between 6-month-old APP and WT mice. Quantitatively, (E) the area occupied by cell bodies in the lateral CA1 region, and (F) the average numbers of cells were not significantly different between APP and WT mice. Statistical analysis used was a two-way ANOVA. Scale bars: 1 mm (low magnification images), 0.05 mm (high magnification images). p < .01, p < .001. Error bars: SEM, pio: pioglitazone, WT: wild-type.
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f0025: Alterations in midline-adjacent CA1 area of the hippocampus in APP mice. (A) Nissl-stained hippocampal sections reveal disorganization of cells in the midline-adjacent CA1 pyramidal layer in 6-month-old APP mice. (B) Compared to age matched control () and pioglitazone-treated () WT mice, the area occupied by cell bodies is significantly reduced in control () and pioglitazone-treated () APP mice. (C) Similarly, irrespective of pioglitazone-treatment status, the average number of cells is significantly lower in APP mice compared to WT mice. (D) No qualitative difference was observed in the lateral CA1 region between 6-month-old APP and WT mice. Quantitatively, (E) the area occupied by cell bodies in the lateral CA1 region, and (F) the average numbers of cells were not significantly different between APP and WT mice. Statistical analysis used was a two-way ANOVA. Scale bars: 1 mm (low magnification images), 0.05 mm (high magnification images). p < .01, p < .001. Error bars: SEM, pio: pioglitazone, WT: wild-type.

Mentions: Qualitatively, Nissl-stained sections revealed irregular spreading of the CA1 pyramidal cells adjacent to the midline into the stratum oriens in 6-month-old APP mice (Fig. 5A). In contrast, there was a sharp demarcation between the CA1 pyramidal cell layer and stratum oriens in WT mice (Fig. 5A). Quantitatively, the percent area of the ROI occupied by cell bodies, and the average number of cells, were significantly reduced (p < 0.05) in APP mice (18.2 ± 2.4% and 188.1 ± 22.1, respectively) compared to WT controls (28.8 ± 0.4% and 329.5 ± 33.4, respectively) (Fig. 5B, C). The average cell size did not differ between APP (198.9 ± 5.0 μm2) and WT (183.1 ± 15.2 μm2) mice. As a negative control, we performed similar histochemical analyses on the lateral region of the CA1, which did not exhibit focal volume decrease (Fig. 4C,F), and found no qualitative (Fig. 5D) nor quantitative differences (Fig. 5E, F) between APP and WT mice.


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

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

Alterations in midline-adjacent CA1 area of the hippocampus in APP mice. (A) Nissl-stained hippocampal sections reveal disorganization of cells in the midline-adjacent CA1 pyramidal layer in 6-month-old APP mice. (B) Compared to age matched control () and pioglitazone-treated () WT mice, the area occupied by cell bodies is significantly reduced in control () and pioglitazone-treated () APP mice. (C) Similarly, irrespective of pioglitazone-treatment status, the average number of cells is significantly lower in APP mice compared to WT mice. (D) No qualitative difference was observed in the lateral CA1 region between 6-month-old APP and WT mice. Quantitatively, (E) the area occupied by cell bodies in the lateral CA1 region, and (F) the average numbers of cells were not significantly different between APP and WT mice. Statistical analysis used was a two-way ANOVA. Scale bars: 1 mm (low magnification images), 0.05 mm (high magnification images). p < .01, p < .001. Error bars: SEM, pio: pioglitazone, WT: wild-type.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f0025: Alterations in midline-adjacent CA1 area of the hippocampus in APP mice. (A) Nissl-stained hippocampal sections reveal disorganization of cells in the midline-adjacent CA1 pyramidal layer in 6-month-old APP mice. (B) Compared to age matched control () and pioglitazone-treated () WT mice, the area occupied by cell bodies is significantly reduced in control () and pioglitazone-treated () APP mice. (C) Similarly, irrespective of pioglitazone-treatment status, the average number of cells is significantly lower in APP mice compared to WT mice. (D) No qualitative difference was observed in the lateral CA1 region between 6-month-old APP and WT mice. Quantitatively, (E) the area occupied by cell bodies in the lateral CA1 region, and (F) the average numbers of cells were not significantly different between APP and WT mice. Statistical analysis used was a two-way ANOVA. Scale bars: 1 mm (low magnification images), 0.05 mm (high magnification images). p < .01, p < .001. Error bars: SEM, pio: pioglitazone, WT: wild-type.
Mentions: Qualitatively, Nissl-stained sections revealed irregular spreading of the CA1 pyramidal cells adjacent to the midline into the stratum oriens in 6-month-old APP mice (Fig. 5A). In contrast, there was a sharp demarcation between the CA1 pyramidal cell layer and stratum oriens in WT mice (Fig. 5A). Quantitatively, the percent area of the ROI occupied by cell bodies, and the average number of cells, were significantly reduced (p < 0.05) in APP mice (18.2 ± 2.4% and 188.1 ± 22.1, respectively) compared to WT controls (28.8 ± 0.4% and 329.5 ± 33.4, respectively) (Fig. 5B, C). The average cell size did not differ between APP (198.9 ± 5.0 μm2) and WT (183.1 ± 15.2 μm2) mice. As a negative control, we performed similar histochemical analyses on the lateral region of the CA1, which did not exhibit focal volume decrease (Fig. 4C,F), and found no qualitative (Fig. 5D) nor quantitative differences (Fig. 5E, F) between APP and WT mice.

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