Some of the dietary and lifestyle habits that protect neverless against AD probably operate through boosting anti-oxidant mechanisms either directly or indirectly. Glial cells also play important protective roles. Astrocytes are known for their neuroprotective properties, such as release of growth factors, control of potentially neurotoxic transmitters and promotion of neuroprotective effects of oestrogens [54,55], although they have recently been shown in co-cultures of neurons and astrocytes to be critically involved in the toxicity that beta-amyloid has for neurons [56]. Microglia may have altered properties in the ageing brain that enhance their ability to exert neurotoxic effects [57,58].
As reviewed by Iadecola [59], brain endothelial cells have critical roles to play in the fine tuning of oxygen and metabolite supply from the blood to the brain in response to neural activity and in enabling waste products of such activity to be removed. They also exert a protective effect on nerve cells by producing growth factors such as brain-derived neurotrophic factor. These endothelial cells are subjected to oxidative damage and toxic effects of beta-amyloid produced in the brain, which can compromise these functions during ageing and promote endothelial cell autophagy. In transgenic AD in mice there are changes in cerebral blood flow regulation long before there is evidence of beta-amyloid deposition in the brain, suggesting that vascular changes occur at a very early stage in the pathogenesis of genetically determined AD.
Stem cells and neurogenesis In animal experiments, both voluntary exercise and environmental enrichment stimulate adult hippocampal neurogenesis. Running can in part reverse the decrease in neurogenesis observed in aged animals and improves learning in aged animals [60]. Sequentially combining the effects of physical activity with environmental enrichment has been shown to have an additive effect on the number of new neurons in the dentate gyrus AV-951 [61]. Kempermann and colleagues [62] have proposed that continued physical and mental activity maintains a ‘neurogenic reserve’ of potential neurons that may be integrated into the hippocampal network. However, the number of precursor cells that may be recruited is limited by the proliferative cells, whose survival may depend on activity in early life.
This links later life reserve to selleck activity in early life and indicates that early life behaviour can only be partly compensated later. The interaction is reminiscent of Hebb’s original finding that early experience influences problem-solving ability in maturity [63]. New cells in the hippocampus initially express increased synaptic plasticity and it has been claimed that all long-term potentiation in the dentate gyrus originates from new cells; meanwhile, long-term potentiation has been shown to induce adult hippocampal neurogenesis in vivo [62].