REVIEW ARTICLE published: 27 August 2013 doi: 10.3389/fnagi.2013.00043 Of mice and men: neurogenesis, cognition, and Alzheimer’s disease Orly Lazarov 1 * and Robert A. Marr 2 * 1 Department of Anatomy and Cell Biology, College of Medicine,The University of Illinois at Chicago, Chicago, IL, USA 2 Department of Neuroscience, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA Edited by: Philip B. Gorelick, University of Chicago, USA Reviewed by: Ashok K. Shetty,Texas A&M Health Science Center, USA Philip B. Gorelick, University of Chicago, USA *Correspondence: Orly Lazarov, Department of Anatomy and Cell Biology, College of Medicine, The University of Illinois at Chicago, 808 South Wood Street, Chicago, IL 60612, USA e-mail: olazarov@uic.edu; Robert A. Marr, Department of Neuroscience, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064, USA e-mail: robert.marr@rosalindfranklin.edu Neural stem cells are maintained in the subgranular layer of the dentate gyrus and in the subventricular zone in the adult mammalian brain throughout life. Neurogenesis is continuous, but its extent is tightly regulated by environmental factors, behavior, hormonal state, age, and brain health. Increasing evidence supports a role for new neurons in cognitive function in rodents. Recent evidence delineates significant similarities and differences between adult neurogenesis in rodents and humans. Being context-dependent, neurogenesis in the human brain might be manifested differently than in the rodent brain. Decline in neurogenesis may play a role in cognitive deterioration, leading to the development of progressive learning and memory disorders, such as Alzheimer’s disease. This review discusses the different observations concerning neurogenesis in the rodent and human brain, and their functional implications for the healthy and diseased brain. Keywords: cognition, learning and memory, aging,Alzheimer’s disease, neurodegenerative disease INTRODUCTION In the adult rodent brain, neural stem cells (NSC) in the sub- ventricular zone (SVZ) and the subgranular layer (SGL) of the dentate gyrus (DG) give rise to new neurons and glia throughout life. From the SVZ, neural progenitor cells (NPC) migrate in chains through the rostral migratory stream (RMS), reach the olfactory bulb (OB) and incorporate there as mature neurons (Ihrie and Alvarez-Buylla, 2011). In the SGL, NPC migrate a short distance to the granular cell layer (GCL) of the DG and incorporate there as mature neurons ( Yao et al., 2012). Similar observations were reported in the primate brain and in the fetal human brain (Kornack and Rakic, 2001; Pencea et al., 2001; Bedard et al., 2002; Sawamoto et al., 2011; Wang et al., 2011). It is now established that neurogenesis takes place in the adult human brain. This was first described in the human hippocampus in post-mortem sections of cancer patients that were injected with 5-bromo-2 ′ -deoxyuridine (BrdU; Eriksson et al., 1998). NSC exist in the human brain throughout life. Similar to rodents, human NPC, including those from hippocampus (Johansson et al., 1999; Kukekov et al., 1999; Palmer et al., 2001), SVZ (Johansson et al., 1999; Kukekov et al., 1999; Roy et al., 2000), OB (Pagano et al., 2000), forebrain subcortical white matter (Nunes et al., 2003), cor- tical and subcortical areas in the temporal lobe (Kirschenbaum et al., 1994), give rise to new neurons and glia. However, the fate and organization of these NPC, the extent of neurogenesis, and its course throughout adulthood are a matter of debate. SUBVENTRICULAR ZONE AND OLFACTORY BULB Some studies observed neurogenesis in the OB and neuroblasts in the RMS (Bedard and Parent, 2004) and a remarkable resem- blance between the mouse and human RMS through which NPC migrate from the SVZ to the OB during aging (Curtis et al., 2007). However, Wang et al. (2011) find an RMS-like in the adult human brain, but neuroblasts do not seem to get to the OB, and their fate along the ventral olfactory tract is unclear. Additionally, Wang et al. (2011) find only a small number of migratory neuroblasts in the SVZ and RMS and they do not form chains. Instead, possess- ing the typical migratory morphology, they move along as single cells or as pairs. These migrating neuroblasts express the immature neuronal markers doublecortin (DCX), polysialylated neural cell adhesion molecule (PSA-NCAM) and class III beta-tubulin (Tuj1) and some of them express proliferation markers (e.g., Ki67; Wang et al., 2011). Several studies describe a ribbon of astrocytes that lines the lateral ventricle in the adult human brain (Sanai et al., 2004; Quinones-Hinojosa et al., 2006). Based on proliferating cell nuclear antigen (PCNA) and Ki67 expression, some of these astro- cytes seem to proliferate, but do not migrate in chains, and only a small number of them express Tuj1 and exhibit migratory mor- phology (Sanai et al., 2004; Quinones-Hinojosa et al., 2006). While exhibiting multipotency in vitro, neuroblasts derived from astro- cytes in the SVZ do not seem to migrate to the OB (Sanai et al., 2004). Follow up studies suggest that active neurogenesis takes place in the post-natal SVZ up to 6 months of age, and then declines drastically (Sanai et al., 2011). Furthermore, in infants Frontiers in Aging Neuroscience www.frontiersin.org August 2013 | Volume 5 | Article 43 | 1