Adult hippocampal neurogenesis and cognitive flexibility — linking memory and mood

Anacker, Christoph; Hen, René

doi:10.1038/nrn.2017.45

Cited by 811 publications

(697 citation statements)

References 193 publications

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“…Neurogenesis is a biological process beginning from neural stem cells to mature neuron formation. This process is necessary for the development of the nervous system to ensure proper cognitive functions, such as behavior, mood, memory , and brain plasticity .…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial dysfunction increases fatty acid β‐oxidation and translates into impaired neuroblast maturation

et al. 2019

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The metabolic transition from anaerobic glycolysis and fatty acid β‐oxidation to glycolysis coupled to oxidative phosphorylation is a key process for the transition of quiescent neural stem cells to proliferative neural progenitor cells. However, a full characterization of the metabolic shift and the involvement of mitochondria during the last step of neurogenesis, from neuroblasts to neuron maturation, is still elusive. Here, we describe a model of neuroblasts, Neuro2a cells, with impaired differentiation capacity due to mitochondrial dysfunction. Using a detailed biochemical characterization consisting of steady‐state metabolomics and metabolic flux analysis, we find increased fatty acid β‐oxidation as a peculiar feature of neuroblasts with altered mitochondria. The consequent metabolic switch favors neuroblast proliferation at the expense of neuron maturation.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial dysfunction increases fatty acid β‐oxidation and translates into impaired neuroblast maturation

et al. 2019

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“…Though unexpected, other studies have also shown varying degrees of sexual dimorphism in hippocampal structure and function (Cushman et al 2012; Galea 2008; Luine et al 2017). While the DNTP radial-arm maze task has been shown to be both hippocampal- and neurogenesis-dependent, conflicting views exist on whether it can properly assess pattern separation processes (Anacker and Hen 2017; Besnard and Sahay 2016; Clelland et al 2009; Santoro 2013), or more broadly spatial discrimination or other hippocampal functions. However, the fact that sexual dimorphism disappears in this assessment when the α7 nAChR is removed remains interesting.…”

Section: Discussionmentioning

confidence: 99%

The α7 nicotinic acetylcholine receptors regulate hippocampal adult-neurogenesis in a sexually dimorphic fashion

Otto

Yakel

2018

Brain Struct Funct

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Disruption in cholinergic signaling has been linked to many environmental and/or pathological conditions known to modify adult neurogenesis. The α7 nAChRs are in the family of cys-loop receptor channels which have been shown to be neuroprotective in adult neurons and are thought to be critical for survival and integration of immature neurons. However, in developing neurons, poor calcium buffering may cause α7 nAChR activation to be neurotoxic. To investigate whether the α7 nAChR regulates neurogenesis in the hippocampus, we used a combination of mouse genetics and imaging to quantify neural stem cell (NSC) densities located in the dentate gyrus of adult mice. In addition, we considered whether the loss of α7 nAChRs had functional consequences on a spatial discrimination task that is thought to rely on pattern separation mechanisms. We found that the loss of α7 nAChRs resulted in increased neurogenesis in male mice only, while female mice showed increased cell divisions and intermediate progenitors but no change in neurogenesis. Knocking out the α7 nAChR from nestin+ NSCs and their progeny showed signaling in these cells contributes to regulating neurogenesis. In addition, male, but not female, mice lacking α7 nAChRs performed significantly worse in the spatial discrimination task. This task was sexually dimorphic in wild-type mice, but not in the absence of α7 nAChRs. We conclude that α7 nAChRs regulate adult neurogenesis and impact spatial discrimination function in male, but not female mice, via a mechanism involving nestin+ NSCs and their progeny.

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“…The CA4 region, also known as the hilus, receives inputs from the granule cells of the dentate gyrus (Amaral, 1978) and major excitatory input from the cortex. The dentate gyrus plays a vital role in neurogenesis (Aimone, Deng, & Gage, 2014), and is linked with memory formation (Anacker & Hen, 2017 We performed a whole-brain connectome analysis using NBS and DTI to identify altered connections and networks and volumetric analysis of the hippocampal subfields to determine changes associated with vitamin D deficiency. The dentate gyrus plays a vital role in neurogenesis (Aimone, Deng, & Gage, 2014), and is linked with memory formation (Anacker & Hen, 2017 We performed a whole-brain connectome analysis using NBS and DTI to identify altered connections and networks and volumetric analysis of the hippocampal subfields to determine changes associated with vitamin D deficiency.…”

Section: Hippocampal Volume Loss Is Associated With Disrupted Netwomentioning

confidence: 99%

Vitamin D deficiency is associated with reduced hippocampal volume and disrupted structural connectivity in patients with mild cognitive impairment

Al-Amin

Bradford

Sullivan

et al. 2018

Human Brain Mapping

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Vitamin D deficiency may exacerbate adverse neurocognitive outcomes in the progression of diseases such as Parkinson's, Alzheimer's, and other dementias. Mild cognitive impairment (MCI) is prodromal for these neurocognitive disorders and neuroimaging studies suggest that, in the elderly, this cognitive impairment is associated with a reduction in hippocampal volume and white matter structural integrity. To test whether vitamin D is associated with neuroanatomical correlates of MCI, we analyzed an existing structural and diffusion MRI dataset of elderly patients with MCI. Based on serum 25‐OHD levels, patients were categorized into serum 25‐OHD deficient (<12 ng/mL, n = 27) or not‐deficient (>12 ng/mL, n = 29). Freesurfer 6.0 was used to parcellate the whole brain into 164 structures and segment the hippocampal subfields. Whole‐brain structural connectomes were generated using probabilistic tractography with MRtrix. The network‐based statistic (NBS) was used to identify subnetworks of connections that significantly differed between the groups. We found a significant reduction in total hippocampal volume in the serum 25‐OHD deficient group especially in the CA1, molecular layer, dentate gyrus, and fimbria. We observed a connection deficit in 13 regions with the right hippocampus at the center of the disrupted network. Our results demonstrate that low vitamin D is associated with reduced volumes of hippocampal subfields and connection deficits in elderly people with MCI, which may exacerbate neurocognitive outcomes. Longitudinal studies are now required to determine if vitamin D can serve as a biomarker for Alzheimer's disease and if intervention can prevent the progression from MCI to major cognitive disorders.

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Adult hippocampal neurogenesis and cognitive flexibility — linking memory and mood

Cited by 811 publications

References 193 publications

Mitochondrial dysfunction increases fatty acid β‐oxidation and translates into impaired neuroblast maturation

Mitochondrial dysfunction increases fatty acid β‐oxidation and translates into impaired neuroblast maturation

The α7 nicotinic acetylcholine receptors regulate hippocampal adult-neurogenesis in a sexually dimorphic fashion

Vitamin D deficiency is associated with reduced hippocampal volume and disrupted structural connectivity in patients with mild cognitive impairment

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