Evidence on adult mammalian neurogenesis and scarce studies with human brains led to the idea that adult human neurogenesis occurs in the subgranular zone (SGZ) of the dentate gyrus and in the subventricular zone (SVZ). However, findings published from 2018 rekindled controversies on adult human SGZ neurogenesis. We systematically reviewed studies published during the first decade of characterization of adult human neurogenesis (1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004) -when the two-neurogenic-niche concept in humans was consolidated -and compared with further studies. The synthesis of both periods is that adult human neurogenesis occurs in an intensity ranging from practically zero to a level comparable to adult mammalian neurogenesis in general, which is the prevailing conclusion. Nonetheless, Bernier and colleagues showed in 2000 intriguing indications of adult human neurogenesis in a broad area including the limbic system. Likewise, we later showed evidence that limbic and hypothalamic structures surrounding the circumventricular organs form a continuous zone expressing neurogenesis markers encompassing the SGZ and SVZ. The conclusion is that publications from 2018 on adult human neurogenesis did not bring novel findings on location of neurogenic niches. Rather, we expect that the search of neurogenesis beyond the canonical adult mammalian neurogenic niches will confirm our indications that adult human neurogenesis is orchestrated in a broad brain area. We predict that this approach may, for example, clarify that human hippocampal neurogenesis occurs mostly in the CA1subiculum zone and that the previously identified human rostral migratory stream arising from the SVZ is indeed the column of the fornix expressing neurogenesis markers.

Evidence on adult mammalian neurogenesis and scarce studies with human brains led to the idea that adult human neurogenesis occurs in the subgranular zone (SGZ) of the dentate gyrus and in the subventricular zone (SVZ). However, findings published from 2018 rekindled controversies on adult human SGZ neurogenesis. We systematically reviewed studies published during the first decade of characterization of adult human neurogenesis (1994–2004) – when the two-neurogenic-niche concept in humans was consolidated – and compared with further studies. The synthesis of both periods is that adult human neurogenesis occurs in an intensity ranging from practically zero to a level comparable to adult mammalian neurogenesis in general, which is the prevailing conclusion. Nonetheless, Bernier and colleagues showed in 2000 intriguing indications of adult human neurogenesis in a broad area including the limbic system. Likewise, we later showed evidence that limbic and hypothalamic structures surrounding the circumventricular organs form a continuous zone expressing neurogenesis markers encompassing the SGZ and SVZ. The conclusion is that publications from 2018 on adult human neurogenesis did not bring novel findings on location of neurogenic niches. Rather, we expect that the search of neurogenesis beyond the canonical adult mammalian neurogenic niches will confirm our indications that adult human neurogenesis is orchestrated in a broad brain area. We predict that this approach may, for example, clarify that human hippocampal neurogenesis occurs mostly in the CA1-subiculum zone and that the previously identified human rostral migratory stream arising from the SVZ is indeed the column of the fornix expressing neurogenesis markers.

Microcephaly has been regarded the most remarkable consequence of the Zika virus (ZIKV) epidemic in Brazil 2015. It remains to be determined whether there are factors that contribute to the degree of brain lesion associated with ZIKV infection during pregnancy. Previous studies showed that socioeconomic conditions correlate with ZIKV-associated microcephaly. Certain nutritional deficits display the potential to interfere in the mechanistic target of rapamycin (mTOR) signaling, which plays a major role in the pathophysiology of ZIKV-associated microcephaly. We hypothesize that a nutritional or environmental co-factor that interferes in mTOR signaling correlates with ZIKV-associated birth defects. To assess this hypothesis, we plan to: 1) develop a mouse model of ZIKV-associated microcephaly through intravenous injection of ZIKV and rapamycin for a straightforward interference on mTOR receptor; 2) determine in the experimental model and in cases of ZIKV-associated microcephaly the epigenetic signature (DNA methylation pattern) in neurons and muscle cells harvested by biopsy, and in hematopoietic and mesenchymal stem cells sorted from blood; 3) analyze through mass spectrometry in serum of pregnant female mice submitted to ZIKV and rapamycin injection and in serum of mothers of children with ZIKV-associated microcephaly the metabolomic pattern of cholesterol (a nutritional status marker), vitamin A and its metabolite retinoic acid, folate, and other metabolites related to these three nutritional factors; 4) check whether pregnant female mice submitted to intravenous injection of ZIKV and feed with a deficient diet of the most likely co-factor found in this study give birth to microcephalic mice with features that mimic clinical cases. In summary, our general objective is to develop an experimental model that mimics ZIKV-associated microcephaly cases and to find a co-factor involved in the microcephaly outbreak in Brazil 2015.