title: Selective impairment of working memory in a mouse model of chronic cerebral hypoperfusion.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Neurology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Masunari
authors.initials: M
authors.lastname: Shibata
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamasaki
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miyakawa
authors.forename: Rajesh N
authors.initials: RN
authors.lastname: Kalaria
authors.forename: Youshi
authors.initials: Y
authors.lastname: Fujita
authors.forename: Ryo
authors.initials: R
authors.lastname: Ohtani
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ihara
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takahashi
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Tomimoto
mesh_terms: D000818:Animals; D016893:Carotid Stenosis / Q000503:physiopathology*; D002908:Chronic Disease; D003213:Conditioning, Psychological / Q000502:physiology; D015140:Dementia, Vascular / Q000503:physiopathology*; D004195:Disease Models, Animal; D005239:Fear / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008570:Memory, Short-Term / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology; D009619:Nociceptors / Q000502:physiology; D012018:Reflex / Q000502:physiology; D013550:Swimming / Q000502:physiology