title: A cognitive rehabilitation paradigm effective in male rats lacks efficacy in female rats.
abstract: Cognitive dysfunction, as a consequence of dementia, is a significant cause of morbidity lacking efficacious treatment. Females comprise at least half of this demographic but have been vastly underrepresented in preclinical studies. The current study addressed this gap by assessing the protective efficacy of physical exercise and cognitive activity on learning and memory outcomes in a rat model of vascular dementia. Forty ovariectomized Sprague-Dawley rats (∼6 months old) were exposed to either a diet high in saturated fats and refined sugars or standard laboratory chow and underwent either chronic bilateral carotid occlusion or Sham surgery. Learning and memory abilities were evaluated using standard cognitive outcomes over the ensuing 6 months, followed by histologic analyses of hippocampal CA1 neurons. In Experiment 1, we confirmed hypoperfusion-induced cognitive dysfunction using a 2 × 2 (Surgery × Diet) experimental design, without alterations in hippocampal architecture. In Experiment 2, hypoperfused animals were either exposed to alternating days of physical (wheel running) and cognitive activity (modified Hebb-Williams maze) or sedentary housing. In contrast to males, this combination rehabilitation paradigm did not improve cognition or histopathologic outcomes in hypoperfused animals. These findings, highlighting differences between female and male animals, show the necessity of including both sexes in preclinical experimentation.
authors: 1] Division of BioMedical Sciences, Memorial University, St John's, Newfoundland and Labrador, Canada [2] Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Ottawa, Ontario, Canada.
authors: Kristopher D
authors: KD
authors: Langdon
authors: Division of BioMedical Sciences, Memorial University, St John's, Newfoundland and Labrador, Canada.
authors: Shirley
authors: S
authors: Granter-Button
authors: Department of Psychology, Memorial University, St John's, Newfoundland and Labrador, Canada.
authors: Carolyn W
authors: CW
authors: Harley
authors: Division of BioMedical Sciences, Memorial University, St John's, Newfoundland and Labrador, Canada.
authors: Frances
authors: F
authors: Moody-Corbett
authors: 1] Department of Radiology, University of Manitoba, Winnipeg, Manitoba, Canada [2] Department of Chemistry, University of Winnipeg, Winnipeg, Manitoba, Canada.
authors: James
authors: J
authors: Peeling
authors: 1] Division of BioMedical Sciences, Memorial University, St John's, Newfoundland and Labrador, Canada [2] Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Ottawa, Ontario, Canada [3] Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada [4] Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors: Dale
authors: D
authors: Corbett
mesh_terms: D000818:Animals; D003071:Cognition; D015928:Cognitive Behavioral Therapy; D015140:Dementia, Vascular / Q000473:pathology / Q000503:physiopathology / Q000534:rehabilitation*; D004032:Diet / Q000009:adverse effects; D005081:Exercise Therapy; D005260:Female; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology; D008297:Male; D018782:Maze Learning; D008568:Memory; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors