Alzheimer's Disease and Hippocampal Adult Neurogenesis; Exploring Shared Mechanisms

Hollands, Carolyn; Bartolotti, Nancy; Lazarov, Orly

doi:10.3389/fnins.2016.00178

Cited by 138 publications

(108 citation statements)

References 111 publications

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“…NSCs can be induced to differentiate through excitation (Deisseroth et al 2004), but activated neurons may differentiate into astrocytes, leading to decreases in the NSC pool and a loss of neurogenic potential (Encinas et al 2011). Pathogenic conditions that impact adult neurogenesis (Hollands et al 2016; Jessberger and Parent 2015; Kang et al 2016) are also linked to the disruption in cholinergic innervation. The dentate gyrus receives input from the basal forebrain through GABAergic and cholinergic projection neurons (Bao et al 2017; Cooper-Kuhn et al 2004), and the infusion of fibroblasts releasing acetylcholine (ACh) into the hippocampus reverses cognitive decline (Dickinson-Anson et al 2003).…”

Section: Introductionmentioning

confidence: 99%

“…In particular, the α7 nAChR is implicated in diseases such as epilepsy, autism, schizophrenia (Adams et al 2012), and Alzheimer’s disease (Dineley et al 2015). These disorders also show altered adult neuro-genesis in the subgranular zone of the dentate gyrus (Hollands et al 2016; Jessberger and Parent 2015; Kang et al 2016). The α7 nAChR may also be neuroprotective (Hernandez et al 2010) in adult neurons; activation of this receptor guides the normal maturation and integration of immature neurons (Campbell et al 2010), thereby promoting their survival.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

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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“…At the cellular level, the change in Np immunoreactivity in AD hippocampi was found to be associated mostly with neurons of the pyramidal sublayer in CA1, CA2/3, and subiculum, and with DG granule cells (Figure ; Table ). In the dentate gyrus, hippocampal area known to be a site of adult neurogenesis and intensive plasticity, increased Np immunoreactivity was predominantly associated with dendrites of granule cells in the inner molecular layer (Figure ). Additional detected changes of Np expression in AD hippocampi included accumulation of immunoreactive intracellular structures in the subicular pyramidal layer (Figure ).…”

Section: Resultsmentioning

confidence: 99%

“…As with other CAMs, it is presumed that Np is involved in the molecular events which underlay the structural and functional processes of brain development, ageing, and neurodegeneration . The adult human hippocampus retains a neuroplastic potential which enables it to remodel and reorganize after injury . This has led us to believe that neuroplastin expression changes during neurodegeneration as well.…”

Section: Introductionmentioning

confidence: 99%

Hippocampal expression of cell‐adhesion glycoprotein neuroplastin is altered in Alzheimer's disease

Ilić

Mlinac-Jerkovic

Jovanov-Milošević

et al. 2018

J Cellular Molecular Medi

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Cell‐adhesion glycoprotein neuroplastin (Np) is involved in the regulation of synaptic plasticity and balancing hippocampal excitatory/inhibitory inputs which aids in the process of associative memory formation and learning. Our recent findings show that neuroplastin expression in the adult human hippocampus is specifically associated with major hippocampal excitatory pathways and is related to neuronal calcium regulation. Here, we investigated the hippocampal expression of brain‐specific neuroplastin isoform (Np65), its relationship with amyloid and tau pathology in Alzheimer's disease (AD), and potential involvement of neuroplastin in tissue response during the disease progression. Np65 expression and localization was analysed in six human hippocampi with confirmed AD neuropathology, and six age‐/gender‐matched control hippocampi by imunohistochemistry. In AD cases with shorter disease duration, the Np65 immunoreactivity was significantly increased in the dentate gyrus (DG), Cornu Ammonis 2/3 (CA2/3), and subiculum, with the highest level of Np expression being located on the dendrites of granule cells and subicular pyramidal neurons. Changes in the expression of neuroplastin in AD hippocampal areas seem to be related to the progression of disease. Our study suggests that cell‐adhesion protein neuroplastin is involved in tissue reorganization and is a potential molecular marker of plasticity response in the early neurodegeneration process of AD.

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“…Aβ peptides are generated by interplay of various secretases cleaving amyloid precursor protein (APP) [2]. Crucial steps in APP processing occur at the cell surface and in the transGolgi network TGN.…”

Section: Introductionmentioning

confidence: 99%

Establishment of a New Rat Model of Alzheimer

2016

IJSR

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Copper is of great importance for the normal brain. Excess of copper results in neurodegenerative diseases such asAlzheimer's disease (AD). The pathological hallmarks of AD are the amyloid-β (Aβ) peptides. Aβ peptides have been shown to bind copper with high affinity. We established a new rat model of AD by using copper sulfate (CuSO 4 ) solution with several doses and for different periods of time. The rats were randomly divided into normal control groups and AD groups. All rats underwent behavioral, histopathological and biochemical evaluations. The results of behavioral test revealed a significant improvement in the normal control groups. Conversely, AD groups showed impairments in the cognitive function as well as spatial memory with several degrees according to the duration and dose of CuSO 4 administration. The precise dose of CuSO 4 that showed the most cognitive deficits was 6 mg/L for eight weeks. Histochemistry staining revealed neuronal abnormalities in the brain sections of AD groups with several degrees. Biochemical analysis demonstrated that the level of γ-secretase was highest at a dose 6 mg/L CuSO 4 for eight weeks, conversely, the level of α-secretase was lowest at the same dose. We conclude that copper appeared to have a role in the formation of senile plaques, the hall mark of AD. According to these issues, we established a new rat model of AD using CuSO 4 solution.

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Alzheimer's Disease and Hippocampal Adult Neurogenesis; Exploring Shared Mechanisms

Cited by 138 publications

References 111 publications

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

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

Hippocampal expression of cell‐adhesion glycoprotein neuroplastin is altered in Alzheimer's disease

Establishment of a New Rat Model of Alzheimer

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