Zinc Distribution and Expression Pattern of ZnT3 in Mouse Brain

Shen, Hui; Wang, Fudi; Zhang, Yuanxun; Xu, Jiajun; Long, Jiangang; Qin, Haigong; Liu, Fang; Guo, Junsheng

doi:10.1007/s12011-007-0056-2

Cited by 28 publications

(15 citation statements)

References 22 publications

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“…In contrast, only labile, vesicular Zn is visualized by histochemical, histofluorescent [7,15] and immunofluorescent staining methods [34,39,44]. Since the labile Zn pool comprises only ~5% [16] to ~20% of total Zn [7], plasticity associated changes in Zn concentration may be below the detection limits of XFI due to the relatively small change relative to the total Zn level.…”

Section: Discussionmentioning

confidence: 99%

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Mapping the dynamics of cortical neuroplasticity of skilled motor learning using micro X-ray fluorescence and histofluorescence imaging of zinc in the rat

Alaverdashvili

Paterson

2017

Behavioural Brain Research

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Synchrotron-based X-ray fluorescence imaging (XFI) of zinc (Zn) has been recently implemented to understand the efficiency of various therapeutic interventions targeting post-stroke neuroprotection and neuroplasticity. However, it is uncertain if micro XFI can resolve neuroplasticity-induced changes. Thus, we explored if learning-associated behavioral changes would be accompanied by changes in cortical Zn concentration measured by XFI in healthy adult rats. Proficiency in a skilled reach-to-eat task during early and late stages of motor learning served as a functional measure of neuroplasticity. c-Fos protein and vesicular Zn expression were employed as indirect neuronal measures of brain plasticity. A total Zn map (20 × 20 × 30 μm3 resolution) generated by micro XFI failed to reflect increases in either c-Fos or vesicular Zn in the motor cortex contralateral to the trained forelimb or improved proficiency in the skilled reaching task. Remarkably, vesicular Zn increased in the late stage of motor learning along with a concurrent decrease in the number of c-fos-ip neurons relative to the early stage of motor learning. This inverse dynamics of c-fos and vesicular Zn level as the motor skill advances suggest that a qualitatively different neural population, comprised of fewer active but more efficiently connected neurons, supports a skilled action in the late versus early stage of motor learning. The lack of sensitivity of the XFI-generated Zn map to visualize the plasticity-associated changes in vesicular Zn suggests that the Zn level measured by micro XFI should not be used as a surrogate marker of neuroplasticity in response to the acquisition of skilled motor actions. Nanoscopic XFI could be explored in future as a means of imaging these subtle physiological changes.

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Section: Discussionmentioning

confidence: 99%

“…Zn can be visualized using various staining techniques. Histochemical [7] and immunofluorescent staining methods [34,39,44] visualize primarily labile Zn. However, these methods also stain other divalent metal cations, including Ca +2 [10,38,47], which can overestimate the role of Zn in brain plasticity.…”

Section: Introductionmentioning

confidence: 99%

Mapping the dynamics of cortical neuroplasticity of skilled motor learning using micro X-ray fluorescence and histofluorescence imaging of zinc in the rat

Alaverdashvili

Paterson

2017

Behavioural Brain Research

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“…Firstly, it was reported that Zn-enriched cortical regions detected by XFI correspond to ZnT3 rich terminal boutons (Linkous et al, 2008). Secondly, coincident accumulation of Zn in the vesicles with a zinc-specific pump called ZnT3 has been shown via juxtaposition of histochemically, histo(cyto)fluorescently and immunofluorescently stained brain specimens (Lee et al, 2011; Palmiter et al, 1996; Shen et al, 2007). Although vesicular Zn, the “labile” Zn pool detected by histofluorescence methods, accounts for only approximately 23% of the total Zn in the cortex (Cole et al, 1999), it is considered to represent 95% of the entire histofluorescently reactive Zn pool (Lee et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Laminar-specific distribution of zinc: Evidence for presence of layer IV in forelimb motor cortex in the rat

et al. 2014

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The rat is the most widely studied pre-clinical model system of various neurological and neurodegenerative disorders affecting hand function. Although brain injury to the forelimb region of the motor cortex in rats mostly induces behavioral abnormalities in motor control of hand movements, behavioral deficits in the sensory-motor domain are also observed. This questions the prevailing view that cortical layer IV, a recipient of sensory information from the thalamus, is absent in rat motor cortex. Because zinc-containing neurons are generally not found in pathways that run from the thalamus, an absence of zinc (Zn) in a cortical layer would be suggestive of sensory input from the thalamus. To test this hypothesis, we used synchrotron micro X-ray fluorescence imaging to measure Zn distribution across cortical layers. Zn maps revealed a heterogeneous layered Zn distribution in primary and secondary motor cortices of the forelimb region in the adult rat. Two wider bands with elevated Zn content were separated by a narrow band having reduced Zn content, and this was evident in two rat strains. The Zn distribution pattern was comparable to that in sensorimotor cortex, which is known to contain a well demarcated layer IV. Juxtaposition of Zn maps and the images of brain stained for Nissl bodies revealed a “Zn valley” in primary motor cortex, apparently starting at the ventral border of pyramidal layer III and ending at the close vicinity of layer V. This finding indicates the presence of a conspicuous cortical layer between layers III and V, i.e. layer IV, the presence of which previously has been disputed. The results have implications for the use of rat models to investigate human brain function and neuropathology, such as after stroke. The presence of layer IV in the forelimb region of the motor cortex suggests that therapeutic interventions used in rat models of motor cortex injury should target functional abnormalities in both motor and sensory domains. The finding is also critical for future investigation of the biochemical mechanisms through which therapeutic interventions can enhance neural plasticity, particularly through Zn dependent pathways.

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“…The concentration of free zinc ions in the extracellular space of healthy brain tissue is in the range of 1 to 10 nM, and the cytosolic zinc concentration is in the picomolar range (Frederickson et al 2005). But in the proximity of axon terminals, zinc rises to micromolar levels following release from synaptic vesicles that contain zinc in the millimolar concentration (Shen et al 2007;Linkous et al 2008). Synaptic zinc is involved in signal transmission/transduction across synapses and therefore modulates synaptic transmission and plasticity (Frederickson et al 2005;Besser et al 2009).…”

Section: Zinc In Alzheimer's Diseasementioning

confidence: 99%