Advanced microscopy techniques for quantitative analysis in neuromorphology and neuropathology research: current status and requirements for the future

Lemmens, Marijke A.M.; Steinbusch, Harry W.M.; Rutten, Bart P. F.; Schmitz, Christoph

doi:10.1016/j.jchemneu.2010.06.005

Cited by 12 publications

(13 citation statements)

References 124 publications

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“…Projections and minor corrections in intensity and contrast were made with the Imaris software program (Bitplane AG, Zurich, Switzerland). The whole system and controlling software have been described in more detail previously [24, 43]. …”

Section: Methodsmentioning

confidence: 99%

Age-Related Increase in Levels of 5-Hydroxymethylcytosine in Mouse Hippocampus is Prevented by Caloric Restriction

Chouliaras¹,

Hove²,

Kenis³

et al. 2012

CAR

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Aberrations in epigenetic marks have been associated with aging of the brain while caloric restriction (CR) and upregulation of endogenous antioxidants have been suggested as tools to attenuate the aging process. We have recently observed age-related increases in levels of 5-methylcytidine (5-mC) and DNA methyltransferase 3a (Dnmt3a) in the mouse hippocampus. Most of those age-related changes in these epigenetic relevant markers were prevented by CR but not by transgenic overexpression of the endogenous antioxidant superoxide dismutase 1 (SOD1). As recent work has suggested a distinct role for hydroxymethylation in epigenetic regulation of gene expression in the brain, the current study investigated age-related changes of 5-hydroxymethylcytosine (5-hmC) in the mouse hippocampus, and furthermore tested whether CR and transgenic upregulation of SOD1 affected any age-related changes in 5-hmC. Immunohistochemical analyses of 5-hmC in 12- and 24-month-old wild-type and transgenic mice overexpressing SOD1, which were kept under either a control or a calorie restricted diet, revealed an increase of 5-hmC immunoreactivity occurring with aging in the hippocampal dentate gyrus, CA3 and CA1–2 regions. Moreover, CR, but not overexpression of SOD1, prevented the age-related increase in the CA3 region. These region-specific findings indicate that the aging process in mice is connected with epigenetic changes and suggest that the beneficial actions of CR may be mediated via epigenetic mechanisms such as methylation and hydroxymethylation of DNA.

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Section: Methodsmentioning

confidence: 99%

Age-Related Increase in Levels of 5-Hydroxymethylcytosine in Mouse Hippocampus is Prevented by Caloric Restriction

Chouliaras¹,

Hove²,

Kenis³

et al. 2012

CAR

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“…When utilizing these reagents for immunostaining of the human tissue, it is important to take into account antigenicity, which can be affected by the delayed fixation of the postmortem tissue (Boekhoorn et al, 2006; Liu et al, 2008) and the specificity of the antibodies, which may be related to a particular species (for example, antibodies which work for rodent tissue may not work for human tissue). Ideally, quantification of cells expressing the biomarker of interest should be obtained using unbiased stereology, such as the optical dissector method (Lemmens et al, 2010), although in human samples this goal can be difficult to achieve due to the low number of proliferating cells (Liu et al, 2008). …”

Section: Methods To Assess Neurogenesis In Humansmentioning

confidence: 99%

Adult Human Neurogenesis: From Microscopy to Magnetic Resonance Imaging

Sierra¹,

Encinas²,

Maletić-Savatić³

2011

Front. Neurosci.

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Neural stem cells reside in well-defined areas of the adult human brain and are capable of generating new neurons throughout the life span. In rodents, it is well established that the new born neurons are involved in olfaction as well as in certain forms of memory and learning. In humans, the functional relevance of adult human neurogenesis is being investigated, in particular its implication in the etiopathology of a variety of brain disorders. Adult neurogenesis in the human brain was discovered by utilizing methodologies directly imported from the rodent research, such as immunohistological detection of proliferation and cell-type specific biomarkers in postmortem or biopsy tissue. However, in the vast majority of cases, these methods do not support longitudinal studies; thus, the capacity of the putative stem cells to form new neurons under different disease conditions cannot be tested. More recently, new technologies have been specifically developed for the detection and quantification of neural stem cells in the living human brain. These technologies rely on the use of magnetic resonance imaging, available in hospitals worldwide. Although they require further validation in rodents and primates, these new methods hold the potential to test the contribution of adult human neurogenesis to brain function in both health and disease. This review reports on the current knowledge on adult human neurogenesis. We first review the different methods available to assess human neurogenesis, both ex vivo and in vivo and then appraise the changes of adult neurogenesis in human diseases.

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“…However, manual analysis of spines is prohibitively time consuming and widely subject to operator variability. Recent software packages now can analyze dendrite and spine morphology automatically (for review see Lemmens et al, 2010; Meijering, 2010), greatly reducing manual interventions to initial setup and postanalysis editing. In particular, we utilized NeuronStudio (Rodriguez et al, 2003, 2006, 2008, 2009; Dumitriu et al, 2011) for all automated morphology reconstructions included in this study.…”

mentioning

confidence: 99%

Morphologic evidence for spatially clustered spines in apical dendrites of monkey neocortical pyramidal cells

Yadav

Gao

Rodríguez

et al. 2012

J of Comparative Neurology

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The general organization of neocortical connectivity in rhesus monkey is relatively well understood. However, mounting evidence points to an organizing principle that involves clustered synapses at the level of individual dendrites. Several synaptic plasticity studies have reported cooperative interaction between neighboring synapses on a given dendritic branch, which may potentially induce synapse clusters. Additionally, theoretical models have predicted that such cooperativity is advantageous, in that it greatly enhances a neuron’s computational repertoire. However, largely because of the lack of sufficient morphologic data, the existence of clustered synapses in neurons on a global scale has never been established. The majority of excitatory synapses are found within dendritic spines. In this study, we demonstrate that spine clusters do exist on pyramidal neurons by analyzing the three-dimensional locations of ~40,000 spines on 280 apical dendritic branches in layer III of the rhesus monkey prefrontal cortex. By using clustering algorithms and Monte Carlo simulations, we quantify the probability that the observed extent of clustering does not occur randomly. This provides a measure that tests for spine clustering on a global scale, whenever high-resolution morphologic data are available. Here we demonstrate that spine clusters occur significantly more frequently than expected by pure chance and that spine clustering is concentrated in apical terminal branches. These findings indicate that spine clustering is driven by systematic biological processes. We also found that mushroom-shaped and stubby spines are predominant in clusters on dendritic segments that display prolific clustering, independently supporting a causal link between spine morphology and synaptic clustering.

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Advanced microscopy techniques for quantitative analysis in neuromorphology and neuropathology research: current status and requirements for the future

Cited by 12 publications

References 124 publications

Age-Related Increase in Levels of 5-Hydroxymethylcytosine in Mouse Hippocampus is Prevented by Caloric Restriction

Age-Related Increase in Levels of 5-Hydroxymethylcytosine in Mouse Hippocampus is Prevented by Caloric Restriction

Adult Human Neurogenesis: From Microscopy to Magnetic Resonance Imaging

Morphologic evidence for spatially clustered spines in apical dendrites of monkey neocortical pyramidal cells

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