The effect of amyloidosis-β and ageing on proliferation of neuronal progenitor cells in APP-transgenic mouse hippocampus and in culture

Abstract

Stimulation of endogenous neurogenesis and transplantation of neuronal progenitors (NPs) are considered in therapy of neuronal loss associated with ageing and in neurodegenerative diseases with amyloidosis-β, for example, Alzheimer’s disease and Down syndrome. However, the influence of brain environment altered by ageing and deposits of amyloid-β on proliferation of endogenous and transplanted NPs and their maturation into neurons is not understood. We studied the effect of ageing and development of amyloidosis-β on proliferation of NPs (1) in the granular layer of dentate gyrus in the hippocampi of APP-transgenic mice (Tg9291) before and after development of amyloidosis-β, that is, in mice aged 2–4 months and 9–12 months, respectively, and in age-matched controls; and (2) in culture of NPs isolated from brains of control and Tg9291 mice, aged 3 and 9 months. We found that the number of proliferating NPs was reduced in 9–12-months-old mice, in both control and Tg9291, as compared to 2–4-months-old mice. However, the 9–12-months-old Tg9291 mice with amyloid-β deposits had significantly more proliferating NPs than the age-matched controls. NPs proliferation in culture did not depend on the age, presence of APP-transgene, and amyloidosis-β in donors. The results indicate that the local brain environment influences proliferation of NPs, and development of amyloidosis-β in the neurogenic regions attenuates the age-associated reduction of proliferation of NPs. Identification of the responsible mechanisms may be important for development of a successful therapy of neurodegeneration caused by amyloidosis-β.