Abnormal differentiation of newborn granule cells in age-related working memory impairments

Abstract

Age-related declines in spatial memory have been linked to abnormal functional properties and connectivity of newborn granule cells. However, the relationship between adult neurogenesis, aging, and cognitive performance seems more complex than previously anticipated, likely due to the difficulty of disentangling alterations related to training as such and those associated with cognitive performance. Here, we investigated how different aspects of adult neurogenesis might be related to training, age and cognitive performance amongst aged subjects by comparing behaviourally naïve and tested rats of 3, 6, 24mo of age. We separated aged rats into learning-impaired and -unimpaired groups based on their performance in the Morris water maze to investigate neurogenesis-related morphological and neurochemical changes. We report an age-related decline in cell proliferation and maturation independent of cognitive performance and testing. We confirm an age-related altered differentiation of newborn neurons which was particularly prominent in learning-impaired rats. This was associated with an abnormally prolonged expression of the early progenitor marker Nestin, potentially also affecting maturation, survival/integration of newborn neurons into existing neuronal networks, which might underlie the individual differences in cognitive performance during aging.