Regional and Gender Study of Neuronal Density in Brain during Aging and in Alzheimer's Disease

Martínez‐Pinilla, Eva; Ordóñez, Cristina; Valle, Eva del; Navarro, Ana; Tolivia, Jorge

doi:10.3389/fnagi.2016.00213

Cited by 40 publications

(38 citation statements)

References 63 publications

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“…Possible alternative explanations for this finding include the differing baseline levels in adult NSC populations seen for wild-type females, the potential for differing levels of expression of neuronal markers, differing metabolism of tamoxifen in female mice, or a differing means of regulating adult neurogenesis. Disentangling these possibilities would provide interesting further research, and may also suggest that this as an interesting line of enquiry to pursue when researching neuropsychiatric and neurodegenerative disorders associated with loss of α7 nAChRs that have a sexually dimorphic presentation (Guebel and Torres 2016; Martinez-Pinilla et al 2016). …”

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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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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“…Atrophy of the CA1 region in AD and other forms of dementia is associated with memory loss and spatial disorientation during early stages of the disease [55][56][57]. Sex differences exist in the areas that correlated with AD progress and neuronal density with age in the hippocampus [58]. Negative associations were seen in Alzheimer's patients between Braak stage and CA1 neuronal density in women but not men, while these same associations were seen in the CA3 neuronal density in men but not women [58].…”

Section: Introductionmentioning

confidence: 96%

“…Sex differences exist in the areas that correlated with AD progress and neuronal density with age in the hippocampus [58]. Negative associations were seen in Alzheimer's patients between Braak stage and CA1 neuronal density in women but not men, while these same associations were seen in the CA3 neuronal density in men but not women [58]. In addition, elevated Braak-stage resulted in decreased in CA1 neuronal density in women, but not in men, whereas elevated Braak stage resulted in decreased CA3 neuronal density in men but not in women.…”

Section: Introductionmentioning

confidence: 99%

Sex differences in hippocampal cognition and neurogenesis

Yagi

Galea

2018

Neuropsychopharmacol

249

151

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Sex differences are reported in hippocampal plasticity, cognition, and in a number of disorders that target the integrity of the hippocampus. For example, meta-analyses reveal that males outperform females on hippocampus-dependent tasks in rodents and in humans, furthermore women are more likely to experience greater cognitive decline in Alzheimer's disease and depression, both diseases characterized by hippocampal dysfunction. The hippocampus is a highly plastic structure, important for processing higher order information and is sensitive to the environmental factors such as stress. The structure retains the ability to produce new neurons and this process plays an important role in pattern separation, proactive interference, and cognitive flexibility. Intriguingly, there are prominent sex differences in the level of neurogenesis and the activation of new neurons in response to hippocampus-dependent cognitive tasks in rodents. However, sex differences in spatial performance can be nuanced as animal studies have demonstrated that there are task, and strategy choice dependent sex differences in performance, as well as sex differences in the subregions of the hippocampus influenced by learning. This review discusses sex differences in pattern separation, pattern completion, spatial learning, and links between adult neurogenesis and these cognitive functions of the hippocampus. We emphasize the importance of including both sexes when studying genomic, cellular, and structural mechanisms of the hippocampal function.

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“…Memory loss is the most prominent clinical symptom of Alzheimer's patients, and it is correlated with the neuronal loss in the hippocampal region. The enduring of neuronal loss is correlated with the progression of the disease [63][64][65][66]. Of note, detectable neuronal loss in multiple regions precedes even before the clinical symptoms start to show, they include entorhinal cortex layer II, nucleus basalis of Meynert, and locus coeruleus [63].…”

Section: Alzheimer's Diseasementioning

confidence: 99%

Neuron Cell Death

H¹,

H²,

Sang³

2018

Preprint

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Neuronal cell death in the central nervous system has always been a challenging process to decipher. In physiological condition, neuronal cell death is restricted in the adult brain even as people ages. However, in pathological conditions of various neurodegenerative diseases, the cell death and shrinkage of a specific brain region represent a fundamental pathological feature across different neurodegenerative diseases. In this review, we will briefly go through the general pathways of cell death and describe the evidence of the cell deaths in the context of common neurodegenerative diseases individually, discussing our current understandings of cell death in connecting with the renowned pathogenic proteins, including tau, amyloid-beta, alpha-synuclein, huntingtin, and TDP-43.

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Regional and Gender Study of Neuronal Density in Brain during Aging and in Alzheimer's Disease

Cited by 40 publications

References 63 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

Sex differences in hippocampal cognition and neurogenesis

Neuron Cell Death

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