Acceleration of age-related learning and memory decline in middle-aged CD-1 mice due to maternal exposure to lipopolysaccharide during late pregnancy

• Published in: Behavioural brain research 2011-04, Vol.218 (2), p.267-279
• Main Authors: Chen, Gui-Hai, Wang, Hua, Yang, Qi-Gang, Tao, Fei, Wang, Chao, Xu, De-Xiang
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Aging; Aging - physiology; Alzheimer's disease; Analysis of Variance; Animals; Anxiety - physiopathology; Behavior, Animal - drug effects; Behavior, Animal - physiology; Behavioral psychophysiology; Biological and medical sciences; Cognition - drug effects; Cognition - physiology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; Fundamental and applied biological sciences. Psychology; Learning - drug effects; Lipopolysaccharide; Lipopolysaccharides - administration & dosage; Male; Medical sciences; Mice; Motor Activity - drug effects; Motor Activity - physiology; Mouse; Neurology; Organic mental disorders. Neuropsychology; Pregnancy; Prenatal Exposure Delayed Effects - physiopathology; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Spatial Behavior - drug effects; Spatial Behavior - physiology
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2010.11.001

▶ Using conventional behavioral methods, the hypothesis that prenatal inflammation increase the vulnerability of the brain to later neurodegeneration is tested. ▶ The effects of prenatal challenging of the immune system may have behavioral effects on brain aging in a dose dependent manner. ▶ Maternal exposure to lipopolysaccharide in adequate dose in late gestation can deliver term offspring which experience a normal duration of development and maturation, and an accelerated aged-related impairment in memory and species-typical behaviors. Previous studies have shown that inflammation process involves pathogenesis of Alzheimer's disease (AD). But, the natural AD model of inflammation has not been obtained yet. In the present study, CD-1 mothers intraperitoneally received a 50μg/kg lipopolysaccharide (LPS) or normal saline daily during gestational days 15–17. Body weight of the offspring was recorded at ages of 4–33 weeks. A different battery of behavioral tasks was, respectively, completed at ages of 35, 290 and 400 days. The results showed that there was no significant difference in body weight between LPS-treated and control mice during ages of 4–33 weeks. LPS-treated offspring had similar anxiety and locomotor behaviors, and spatial ability of learning and memory at the age of 35 days compared to the controls. At an age of 290 days, the LPS-treated offspring had similar sensorimotor ability, locomotor activity and anxiety, species-typical behaviors, and spatial ability of learning and memory. At an age of 400 days, there were similar sensorimotor ability, locomotor activity and anxiety between the LPS-treated offspring and controls. However, there were impaired species-typical behaviors, and spatial and non-spatial abilities of learning and memory in the LPS-treated offspring. Our results suggested that maternal exposure to LPS in adequate dose in late gestation can deliver term offspring which experience a normal duration of development and maturation, and an accelerated aged-related impairment in memory (spatial and non-spatial) and species-typical behaviors in middle-aged. These meet with the criteria of AD model in behaviors.