Biomedical subjects

Yongjun Qin

Publications and source records attributed to Yongjun Qin.

5 recordsLinked to original sources

PubMed2006

Glucocorticoids specifically enhance L-type calcium current amplitude and affect calcium channel subunit expression in the mouse hippocampus.

Previous studies have shown that corticosterone enhances whole cell calcium currents in CA1 pyramidal neurons, through a pathway involving binding of glucocorticoid receptor homodimers to the DNA. We examined whether glucocorticoids show selectivity for L- over N-type of calcium currents. Moreover, we addressed the putative gene targets that eventually lead to the enhanced calcium currents. Electrophysiological recordings were performed in nucleated patches that allow excellent voltage control. Calcium currents in these patches almost exclusively involve N- and L-type channels. We found that L- but not N-type calcium currents were largely enhanced after treatment with a high dose of corticosterone sufficient to activate glucocorticoid receptors. Voltage dependency and kinetic properties of the currents were unaffected by the hormone. Nonstationary noise analysis suggests that the increased current is not caused by a larger unitary conductance, but rather to a doubling of the number of functional channels. Quantitative real-time PCR revealed that transcripts of the Ca(v)1 subunits encoding for the N- or L-type calcium channels are not upregulated in the mouse CA1 area; instead, a strong, direct, and consistent upregulation of the beta4 subunit was observed. This indicates that the corticosteroid-induced increase in number of L-type calcium channels is not caused by a simple transcriptional regulation of the pore-forming subunit of the channels.

Animals↗

PubMed2004

Effects of chronic stress on structure and cell function in rat hippocampus and hypothalamus.

It has become increasingly clear that the increase in corticosteroid levels, e.g. after a brief stressor induce molecular and cellular changes in brain, including the hippocampal formation. These effects eventually result in behavioral adaptation. Prolonged exposure to stress, though, may lead to mal-adaptation and even be a risk factor for diseases like major depression in genetically predisposed individuals. We conducted a series of experiments where changes in brain function were examined after 3 weeks of unpredictable stress. After unpredictable stress, inhibitory input to neurons involved in the hypothalamus-pituitary-adrenal (HPA) axis regulation was suppressed, which may dysregulate the axis and lead to overexposure of the brain to glucocorticoids. Furthermore, glutamate transmission in the dentate gyrus (DG) was enhanced, possibly through transcriptional regulation of receptor subunits. Combined with enhanced calcium channel expression this could increase vulnerability to cell death. Neurogenesis and apoptosis in the dentate were diminished. Synaptic plasticity was suppressed both in the dentate and CA1 area. Collectively, these effects may give rise to deficits in memory formation. Finally, we observed reduced responses to serotonin in the CA1 area, which could contribute to the onset of symptoms of depression in predisposed individuals. All of these endpoints provide potential targets for novel treatment strategies of stress-related brain disorders.

Animals↗

PubMed2004

Chronic unpredictable stress alters gene expression in rat single dentate granule cells.

The rat adrenal hormone corticosterone binds to low and high affinity receptors, discretely localized in brain, including the dentate gyrus. Differential activation of the two receptor types under physiological conditions alters gene expression and functional characteristics of hippocampal neurones. In the present study we examined gene expression of electrophysiologically identified dentate granule cells, 1 day after 21 days of unpredictable stress or control treatment, both under basal corticosteroid conditions and after brief in vitro exposure to a high dose of corticosterone. From each cell, RNA was collected, linearly amplified and hybridized with cDNA clones for three calcium channel subunits, four NMDA, two AMPA and 11 GABA receptor subunits. We found that gene expression was not extensively changed after chronic stress when neurones were studied under basal corticosteroid conditions. However, combined with acute exposure to a high corticosterone dose, relative expression of eight transcripts was significantly altered, including a consistent up-regulation of GABAa receptor alpha 1 and down-regulation of calcium channel alpha 1A and alpha 1G subunit expression. If translated to the protein level, this may result in more transient GABAa receptor mediated responses and less transient calcium influx. This could contribute to enhanced excitability and vulnerability of granule cells after chronic stress.

Animals↗

PubMed2003

Gene expression patterns in rat dentate granule cells: comparison between fresh and fixed tissue.

RNA from brain tissue (in particular human brain) can often only be extracted from fixed material. As brain tissue is very heterogeneous with regard to cell type, it is important to obtain RNA from small samples of identified cells. The aim of this study was (a) to generate expression profiles from small yet homogeneous samples of fixed brain cells in rat and (b) to verify the reliability of these profiles by comparing them with expression profiles obtained from single fresh neurons of the same cell type. Samples (n=12) of 50 rat dentate granule cells were isolated, using Laser Microdissection and Pressure Catapulting, from paraformaldehyde fixed, paraffin embedded tissue or from frozen, ethanol fixed tissue. In addition, RNA was extracted under visual control from individual dentate granule cells (n=12) in hippocampal slices, after electrophysiological recording with patch clamp electrodes. Our data show that RNA was successfully extracted from ethanol fixed sections yielding expression profiles highly comparable to those from non-fixed, single granule cells. RNA extraction from paraformaldehyde fixed, paraffin embedded tissue was less reliable. The present approach validates expression profiling from small amounts of fixed neurons as a powerful tool to investigate molecular processes if fresh tissue is not available.

Animals↗

PubMed2003

Gene expression changes in single dentate granule neurons after adrenalectomy of rats.

Removal of corticosterone by adrenalectomy induces apoptosis 3 days later, in some, but not all, rat dentate granule cells. We hypothesized that individual dentate cells trigger specific gene expression profiles that partly determine their apoptosis susceptibility. RNA was collected from physiologically characterized granule cells at 2 or 3 days after adrenalectomy or sham operation, and linearly amplified. The amplified RNA was hybridized to cDNA clones of: (1) candidate genes earlier identified after adrenalectomy in whole hippocampi with SAGE; and (2) genes encoding growth factors and their receptors. We observed that based on the entire expression profile, cells relatively resistant to apoptosis 3 days after adrenalectomy clustered together with one-third of cells 2 days after adrenalectomy. Within the group of ADX cells, a limited number of transcript ratios were found to correlate-positively or negatively-with a known risk factor for apoptosis, calcium influx. The overall analysis of physiological properties and multiple gene expression in single cells can narrow down the number of critical genes involved in apoptosis identified with large scale gene screening methods and allows a first impression of their role as being a potential risk factor or neuroprotective.

Adrenalectomy↗