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Neuroprotective effects of neurosteroids

Neurosteroids and MBR ligands were shown to have neuroprotective effects after excitotoxic brain injury, to which aged brains are particularly vulnerable. Treatment with 3a, 5a-tetrahydroprogesterone not only affected the survival of hippocampal neurons, but also influenced the synaptic remodelling after neuronal loss. The effect seems to be specific for certain type of synapses, as it does differently affect the GABAergic and non-GABAergic terminals.

A significant loss of hilar neurons in the hippocampus of male and female rats has been observed between 22 and 24 months of age. The administration of progestins resulted in a significant reduction in neuronal loss at this age. By using unbiased stereological quantification methods, it was shown that the ageing process of the hippocampus is not only accompanied by neuronal death, but also by changes in synaptic connectivity.

Estradiol also rescued hippocampal neurons after excitotoxic injury, and regulated adult neurogenesis in the hippocampus by acting in synergy with the growth factor IGF-1. The actions of the estradiol and IGF-1 were shown to converge on the intracellular AKT/PKB signalling pathway. The local formation of estradiol by the aromatase enzyme may play an important role.

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