Prenatal Malnutrition and the Aging Brain

Boston University Medical Campus, Boston MA

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): In the elderly population there are many who develop cognitive problems. As the aged population is increasing there is an urgent need to determine if there are any predisposing factors. Evidence from a variety of epidemiological and animal experimental work suggests that individuals who are born small (primarily resulting from prenatal undernutrition) are prone to develop a variety of health problems later in life, e.g., heart disease, hypertension, diabetes and more. A process that has been termed, "prenatal programming". However, whether prenatal undernutrition/malnutrition predisposes individuals to cognitive dysfunction during senescence has not been examined. This is the broad objective of the current project, and will take advantage of a well-established rodent model of prenatal malnutrition. Sub-populations of aged rats are known to develop deficient behavioral performance on tasks that involve the hippocampus and the frontal cortex. It is postulated that prenatal malnutrition will predispose rats to cognitive dysfunction during senescence since there are already indications of behavioral changes consistent with frontal cortical dysfunction in young adulthood, and significant alterations in the structure and function of the hippocampus. Using a cross sectional design (using litter mates) prenatally malnourished and well-nourished rats will be tested in the Morris water maze (hippocampus) and attentional set shifting tasks consisting of simple and compound discriminations, intra-dimensional and extradimensional shifts (medial prefrontal cortex) and in reversals (orbitofrontal cortex), at 12, 18, 24 and 30 months of age. This project is important because the population that lived through the great economic depression suffered many privations, including inadequate nutrition. These individuals are now of a prime age for developing cognitive problems. If it can be established that low birth weight predisposes individuals to greater cognitive decline in old age it may be possible to develop therapeutic strategies to forestall or retard the decline in individuals identified as being "born small."