Selective impairment of working memory in a mouse model of chronic cerebral hypoperfusion

Masunari Shibata, Nobuyuki Yamasaki, Tsuyoshi Miyakawa, Rajesh N. Kalaria, Youshi Fujita, Ryo Ohtani, Masafumi Ihara, Ryosuke Takahashi, Hidekazu Tomimoto

Research output: Contribution to journalArticle

144 Citations (Scopus)

Abstract

BACKGROUND AND PURPOSE - We recently designed a mouse model of chronic cerebral hypoperfusion, in which the cerebral white matter is damaged without significant gray matter lesions. The behavioral characteristics of these mice were studied using a test battery for neurological and cognitive functions. METHODS - Adult C57Bl/6 male mice were subjected to either sham-operation or bilateral common carotid artery stenosis (BCAS) using microcoils with an internal diameter of 0.18 mm. At 30 days after BCAS, 70 animals were divided into 3 groups and subjected to behavioral test batteries. The first group underwent comprehensive behavioral test, including the neurological screen, prepulse inhibition, hot plate, open field, light/dark transition, Porsolt forced swim and contextual and cued fear conditioning (BCAS n=13; sham-operated n=11). The second group was for the working memory task of the 8-arm radial maze test (BCAS n=12; sham-operated n=10), and the third for the reference memory task of the 8-arm radial maze test (BCAS n=13; sham-operated n=11). Another batch of animals were examined for histological changes (BCAS n=11; sham-operated n=12). RESULTS - The white matter including the corpus callosum was consistently found to be rarefied without clear ischemic lesions in the hippocampus. No apparent differences were observed in the comprehensive test batteries between the control and BCAS mice. However, in the working memory tasks tested with the 8-arm radial maze, the BCAS mice made significantly more errors than the control mice (P<0.0001). Again, there were no detectable differences in the reference memory tasks between the groups. CONCLUSIONS - At 30 days after BCAS, working memory deficits as well as white matter changes were apparent in the mice. Working memory deficit was attributable to damage of the frontal-subcortical circuits, suggesting the BCAS model is useful to evaluate the substrates of subcortical vascular dementia.

Original languageEnglish
Pages (from-to)2826-2832
Number of pages7
JournalStroke
Volume38
Issue number10
DOIs
Publication statusPublished - 01-10-2007

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Carotid Stenosis
Short-Term Memory
Memory Disorders
Vascular Dementia
Corpus Callosum
Cognition
Fear
Hippocampus
Light

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialised Nursing

Cite this

Shibata, M., Yamasaki, N., Miyakawa, T., Kalaria, R. N., Fujita, Y., Ohtani, R., ... Tomimoto, H. (2007). Selective impairment of working memory in a mouse model of chronic cerebral hypoperfusion. Stroke, 38(10), 2826-2832. https://doi.org/10.1161/STROKEAHA.107.490151
Shibata, Masunari ; Yamasaki, Nobuyuki ; Miyakawa, Tsuyoshi ; Kalaria, Rajesh N. ; Fujita, Youshi ; Ohtani, Ryo ; Ihara, Masafumi ; Takahashi, Ryosuke ; Tomimoto, Hidekazu. / Selective impairment of working memory in a mouse model of chronic cerebral hypoperfusion. In: Stroke. 2007 ; Vol. 38, No. 10. pp. 2826-2832.
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abstract = "BACKGROUND AND PURPOSE - We recently designed a mouse model of chronic cerebral hypoperfusion, in which the cerebral white matter is damaged without significant gray matter lesions. The behavioral characteristics of these mice were studied using a test battery for neurological and cognitive functions. METHODS - Adult C57Bl/6 male mice were subjected to either sham-operation or bilateral common carotid artery stenosis (BCAS) using microcoils with an internal diameter of 0.18 mm. At 30 days after BCAS, 70 animals were divided into 3 groups and subjected to behavioral test batteries. The first group underwent comprehensive behavioral test, including the neurological screen, prepulse inhibition, hot plate, open field, light/dark transition, Porsolt forced swim and contextual and cued fear conditioning (BCAS n=13; sham-operated n=11). The second group was for the working memory task of the 8-arm radial maze test (BCAS n=12; sham-operated n=10), and the third for the reference memory task of the 8-arm radial maze test (BCAS n=13; sham-operated n=11). Another batch of animals were examined for histological changes (BCAS n=11; sham-operated n=12). RESULTS - The white matter including the corpus callosum was consistently found to be rarefied without clear ischemic lesions in the hippocampus. No apparent differences were observed in the comprehensive test batteries between the control and BCAS mice. However, in the working memory tasks tested with the 8-arm radial maze, the BCAS mice made significantly more errors than the control mice (P<0.0001). Again, there were no detectable differences in the reference memory tasks between the groups. CONCLUSIONS - At 30 days after BCAS, working memory deficits as well as white matter changes were apparent in the mice. Working memory deficit was attributable to damage of the frontal-subcortical circuits, suggesting the BCAS model is useful to evaluate the substrates of subcortical vascular dementia.",
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Shibata, M, Yamasaki, N, Miyakawa, T, Kalaria, RN, Fujita, Y, Ohtani, R, Ihara, M, Takahashi, R & Tomimoto, H 2007, 'Selective impairment of working memory in a mouse model of chronic cerebral hypoperfusion', Stroke, vol. 38, no. 10, pp. 2826-2832. https://doi.org/10.1161/STROKEAHA.107.490151

Selective impairment of working memory in a mouse model of chronic cerebral hypoperfusion. / Shibata, Masunari; Yamasaki, Nobuyuki; Miyakawa, Tsuyoshi; Kalaria, Rajesh N.; Fujita, Youshi; Ohtani, Ryo; Ihara, Masafumi; Takahashi, Ryosuke; Tomimoto, Hidekazu.

In: Stroke, Vol. 38, No. 10, 01.10.2007, p. 2826-2832.

Research output: Contribution to journalArticle

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T1 - Selective impairment of working memory in a mouse model of chronic cerebral hypoperfusion

AU - Shibata, Masunari

AU - Yamasaki, Nobuyuki

AU - Miyakawa, Tsuyoshi

AU - Kalaria, Rajesh N.

AU - Fujita, Youshi

AU - Ohtani, Ryo

AU - Ihara, Masafumi

AU - Takahashi, Ryosuke

AU - Tomimoto, Hidekazu

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Y1 - 2007/10/1

N2 - BACKGROUND AND PURPOSE - We recently designed a mouse model of chronic cerebral hypoperfusion, in which the cerebral white matter is damaged without significant gray matter lesions. The behavioral characteristics of these mice were studied using a test battery for neurological and cognitive functions. METHODS - Adult C57Bl/6 male mice were subjected to either sham-operation or bilateral common carotid artery stenosis (BCAS) using microcoils with an internal diameter of 0.18 mm. At 30 days after BCAS, 70 animals were divided into 3 groups and subjected to behavioral test batteries. The first group underwent comprehensive behavioral test, including the neurological screen, prepulse inhibition, hot plate, open field, light/dark transition, Porsolt forced swim and contextual and cued fear conditioning (BCAS n=13; sham-operated n=11). The second group was for the working memory task of the 8-arm radial maze test (BCAS n=12; sham-operated n=10), and the third for the reference memory task of the 8-arm radial maze test (BCAS n=13; sham-operated n=11). Another batch of animals were examined for histological changes (BCAS n=11; sham-operated n=12). RESULTS - The white matter including the corpus callosum was consistently found to be rarefied without clear ischemic lesions in the hippocampus. No apparent differences were observed in the comprehensive test batteries between the control and BCAS mice. However, in the working memory tasks tested with the 8-arm radial maze, the BCAS mice made significantly more errors than the control mice (P<0.0001). Again, there were no detectable differences in the reference memory tasks between the groups. CONCLUSIONS - At 30 days after BCAS, working memory deficits as well as white matter changes were apparent in the mice. Working memory deficit was attributable to damage of the frontal-subcortical circuits, suggesting the BCAS model is useful to evaluate the substrates of subcortical vascular dementia.

AB - BACKGROUND AND PURPOSE - We recently designed a mouse model of chronic cerebral hypoperfusion, in which the cerebral white matter is damaged without significant gray matter lesions. The behavioral characteristics of these mice were studied using a test battery for neurological and cognitive functions. METHODS - Adult C57Bl/6 male mice were subjected to either sham-operation or bilateral common carotid artery stenosis (BCAS) using microcoils with an internal diameter of 0.18 mm. At 30 days after BCAS, 70 animals were divided into 3 groups and subjected to behavioral test batteries. The first group underwent comprehensive behavioral test, including the neurological screen, prepulse inhibition, hot plate, open field, light/dark transition, Porsolt forced swim and contextual and cued fear conditioning (BCAS n=13; sham-operated n=11). The second group was for the working memory task of the 8-arm radial maze test (BCAS n=12; sham-operated n=10), and the third for the reference memory task of the 8-arm radial maze test (BCAS n=13; sham-operated n=11). Another batch of animals were examined for histological changes (BCAS n=11; sham-operated n=12). RESULTS - The white matter including the corpus callosum was consistently found to be rarefied without clear ischemic lesions in the hippocampus. No apparent differences were observed in the comprehensive test batteries between the control and BCAS mice. However, in the working memory tasks tested with the 8-arm radial maze, the BCAS mice made significantly more errors than the control mice (P<0.0001). Again, there were no detectable differences in the reference memory tasks between the groups. CONCLUSIONS - At 30 days after BCAS, working memory deficits as well as white matter changes were apparent in the mice. Working memory deficit was attributable to damage of the frontal-subcortical circuits, suggesting the BCAS model is useful to evaluate the substrates of subcortical vascular dementia.

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