Our initial work has unveiled the presence of cells that have allowed the reconstruction of the whole adult hippocampal neurogenesis (AHN) process in humans. These cells include neural stem cells (NSCs) (the cells that divide and give rise to neurons), cells that undergoing cell division and maturation, and neurons at distinct stages of maturity. Moreover, we showed that AHN is damaged in patients with distinct neurodegenerative diseases (namely Alzheimer´s disease, Parkinson´s disease, Huntington´s disease, Amyotrophic Lateral Sclerosis, Lewy body dementia, and Frontotemporal dementia). In patients with Alzheimer´s disease, hippocampal neurons show an aberrant morphology that is likely to impede adequate connections with other cells. A similar morphology was observed in the same cells in patients with other neurodegenerative diseases such as Frontotemporal dementia. One of the most striking results observed is that AHN is altered in a very particular way in each of the diseases we have studied. For instance, patients with Amyotrophic Lateral Sclerosis have higher numbers of NSCss, whereas those with other disorders do not show this alteration. Immature neurons are altered, in a variable manner, in all the diseases addressed. For instance, in patients with Huntington´s disease, immature neurons remain at very immature stages, whereas in those with Parkinson´s disease, the most remarkable alterations in these cells appear when they have reached more advanced stages of maturity. The differential alterations observed in each disorder have driven the hypothesis that each neurodegenerative condition triggers the appearance of a unique combination of alterations in AHN, which we refer to as a particular adult hippocampal neurogenesis signature. Moreover, in all the diseases examined, the cells that accompany the newly generated neurons throughout their life (what is called the adult neurogenic niche) show dramatic alterations that point to neuroinflammation as a common factor of most neurodegenerative disorders and aging. All these findings were published (Impact of neurodegenerative diseases on human adult hippocampal neurogenesis. Terreros-Roncal J, Moreno-Jiménez EP, Flor-García M, Rodríguez-Moreno CB, Trinchero MF, Cafini F, Rábano A, Llorens-Martín M. SCIENCE. 2021 Nov 26;374(6571):1106-1113. PMID: 34672693). We are currently studying adult hippocampal alterations in patients with psychiatric disorders.
