, Volume 116, Issue 4, pp 419-424
Date: 16 May 2008

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

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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.