Adult Hippocampal Neurogenesis in Alzheimer’s Disease: An Overview of Human and Animal Studies with Implications for Therapeutic Perspectives Aimed at Memory Recovery

Figure 1

Main steps of AHN. Top left: image representing the position of the dentate gyrus (DG) and its main output target, the CA3 subregion, within the hippocampal circuit. Middle panel: morphological characterization and main markers related to the different cell types that identify the transition of a newborn neuron from a neural stem cell to a mature neuron integrated into a pre-existing circuit. As indicated by the scheme, the different stages undertaken by a newly generated neuron within the hippocampal dentate gyrus are characterized by a peculiar morphological identity and by the expression of specific cell markers (see boxes) that make it possible to study the proliferative and differentiative dynamics finely orchestrating the maturation of newborn neuron. Bottom diagram: neurotransmitters involved in the differentiation and maturation processes of newborn neurons. A first phase characterized by an excitatory GABAergic signaling that enables the maturation of the neural progenitors is followed by an excitatory glutamatergic signaling, which will permanently distinguish the electrophysiological properties of the new-generated granule neurons in the hippocampal dentate gyrus circuit. GFAP: glial fibrillary acidic protein; Sox2: SRY- (sex determining region Y-) box; BLBP: brain lipid binding protein; Neuro D1: neuronal differentiation 1; DCX: doublecortin; PSA-NCAM: polysialylated-neural cell adhesion molecule; NeuN: neuronal nuclear protein; Prox 1: prospero homeobox 1; Ki67: proliferative marker.