Aimone JB, Wiles J, Gage FH. Potential role for adult neurogenesis in the encoding of time in new memories. Nat Neurosci 9: 723-727

Laboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
Nature Neuroscience (Impact Factor: 14.98). 07/2006; 9(6):723-7. DOI: 10.1038/nn1707
Source: PubMed

ABSTRACT The dentate gyrus in the hippocampus is one of two brain regions with lifelong neurogenesis in mammals. Despite an increasing amount of information about the characteristics of the newborn granule cells, the specific contribution of their robust generation to memory formation by the hippocampus remains unclear. We describe here a possible role that this population of young granule cells may have in the formation of temporal associations in memory. Neurogenesis is a continuous process; the newborn population is only composed of the same cells for a short period of time. As time passes, the young neurons mature or die and others are born, gradually changing the identity of this young population. We discuss the possibility that one cognitive impact of this gradually changing population on hippocampal memory formation is the formation of the temporal clusters of long-term episodic memories seen in some human psychological studies.

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    • "In adult neurogenesis, the newly generated neurons integrate multiple signals, form new synapses in the hippocampus (Aimone et al. 2006; van Praag et al. 2002) and are thought to have an important role in learning and memory and in adaptive responses in neurodegenerative disorders (Lazarov et al. 2010). In agreement with these findings, compounds that positively influence neurogenesis are associated with enhanced performance in hippocampal-dependent learning tasks (Ahn et al. 2014; Lee et al. 2013a; Snyder et al. 2005). "
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    ABSTRACT: Exposure to organophosphorous (OP) nerve agents such as soman inhibits the critical enzyme acetylcholinesterase (AChE) leading to excessive acetylcholine accumulation in synapses, resulting in cholinergic crisis, status epilepticus and brain damage in survivors. The hippocampus is profoundly damaged after soman exposure leading to long-term memory deficits. We have previously shown that treatment with three sequential doses of alpha-linolenic acid, an essential omega-3 polyunsaturated fatty acid, increases brain plasticity in naïve animals. However, the effects of this dosing schedule administered after a brain insult and the underlying molecular mechanisms in the hippocampus are unknown. We now show that injection of three sequential doses of alpha-linolenic acid after soman exposure increases the endogenous expression of mature BDNF, activates Akt and the mammalian target of rapamycin complex 1 (mTORC1), increases neurogenesis in the subgranular zone of the dentate gyrus, increases retention latency in the passive avoidance task and increases animal survival. In sharp contrast, while soman exposure also increases mature BDNF, this increase did not activate downstream signaling pathways or neurogenesis. Administration of the inhibitor of mTORC1, rapamycin, blocked the alpha-linolenic acid-induced neurogenesis and the enhanced retention latency but did not affect animal survival. Our results suggest that alpha-linolenic acid induces a long-lasting neurorestorative effect that involves activation of mTORC1 possibly via a BDNF-TrkB-mediated mechanism.
    Neuromolecular medicine 04/2015; DOI:10.1007/s12017-015-8353-y · 3.89 Impact Factor
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    • "Regenerative and reparative therapy has emerged to be an important approach for stroke management (Banerjee et al. 2014, Chang et al. 2007, Lee et al. 2007, Steindler 2007). On one hand, the brain is capable of regenerating neurons after their maturation (Aimone et al. 2006, Allen et al. 2001, Eriksson et al. 1998), and stroke can stimulate neurogenesis (Chopp et al. 2007, Jin et al. 2006, Ohira et al. 2009). On the other hand, stem cell transplantation enhances neurogenesis in the brains and significantly improves cognitive functions in experimental animals (Horie et al. 2011, Roitberg et al. 2006, Theus et al. 2008, Yu et al. 2013). "
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    ABSTRACT: Stress adaptation effect provides cell protection against ischemia induced apoptosis. Whether this mechanism prevents other types of cell death in stroke is not well studied. This is an important question for regenerative medicine to treat stroke since other types of cell death such as necrosis are also prominent in the stroke brain apart from apoptosis. We report here that treatment with 17-N-Allylamino-17-demethoxygeldanamycin (17AAG), an Hsp90 inhibitor, protected neural progenitor cells (NPCs) against oxygen glucose deprivation (OGD) induced cell death in a dose dependent fashion. Cell death assays indicated that 17AAG not only ameliorated apoptosis, but also necrosis mediated by OGD. This NPC protection was confirmed by exposing cells to oxidative stress, a major stress signal prevalent in the stroke brain. Mechanistic studies demonstrated that 17AAG activated PI3K/Akt and MAPK cell protective pathways. More interestingly, these two pathways were activated in vivo by 17AAG and 17AAG treatment reduced infarct volume in a middle cerebral artery occlusion (MCAO) stroke model. These data suggest that 17AAG protects cells against major cell death pathways and thus might be used as a pharmacological conditioning agent for regenerative medicine for stroke.
    Journal of Cell Communication and Signaling 10/2014; DOI:10.1007/s12079-014-0247-5
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    • "In response to inflammatory nociception on postnatal day 1 (P1), the granule cell layer of the hippocampus shows an increase in mitotic rate during adolescence [15] [16] [17], which has raised questions about the role played by hippocampus in the long term nociceptive processing. Dentate granule cells of the hippocampus have been related to the formation of associative memories [1], which are essential to define the semantic properties of stimuli, since the meaning of a stimulus may be associated with other stimuli [2]. It has been demonstrated that chronic pain is associated with the reduction in right hippocampus volume in aged women [8] and that pain interferes in processes of memory encoding, which is associated with reduced activity in the same area, It has been suggested that pain is related to disruption of encoding and, thus, interferes with an early stage of memory formation [9]. "
    Neuroscience Letters 10/2014; 581:135–136. DOI:10.1016/j.neulet.2014.08.013 · 2.06 Impact Factor
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