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Influence of calcium ion increase rate reducing on cell death reducing with penumbral region neuron in CaV2.1 mutant mouse model

A mouse model, a technology of cell death, applied in the field of biomedicine, which can solve problems of different severity and so on

Inactive Publication Date: 2017-06-06
宁波美丽人生医药生物科技发展有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Although rollingNagoya and leaner mutant mice exhibit normal lifespans, their ataxia severity differs significantly, with leaner mutant mice being more severe

Method used

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  • Influence of calcium ion increase rate reducing on cell death reducing with penumbral region neuron in CaV2.1 mutant mouse model
  • Influence of calcium ion increase rate reducing on cell death reducing with penumbral region neuron in CaV2.1 mutant mouse model
  • Influence of calcium ion increase rate reducing on cell death reducing with penumbral region neuron in CaV2.1 mutant mouse model

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Experimental program
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Effect test

Embodiment 1

[0041] Ca V 2. Expression pattern of 1α1 mRNA

[0042] We used in situ hybridization to assess Ca V 2. Distribution of 1α1 mRNA in wild-type mice (n=6), rolling Nagoya (n=5) and leanermice (n=5); the distribution in three kinds of mice is the same (data not shown). We detected a widespread expression of α1 subunit in the brains of these three mice using antisense probes, especially in olfactory bulb neurons, cerebral cortex neurons, hippocampus neurons and cerebellum neurons There are strong expressions. However, no signal was detected after using the sense probe. We used real-timeqRT-PCR to detect Ca V 2. The expression levels of 1α1mRNA in the olfactory bulb, cerebral cortex, caudate putamen, hippocampus, cerebellum and liver in these three kinds of mice. In the olfactory bulb, cerebral cortex, caudate putamen, hippocampus, and cerebellum of these three mice, total Ca V 2. The relative expression level of 1α1 is not significantly different, (the values ​​of wild-type m...

Embodiment 2

[0044] Ca V 2.1α1 Gene Mutant Mice Reduced Infarct Volume in In vivo Ischemia Model

[0045] Wild-type mice (n=12), rolling Nagoya (n=11) and leanermice (n=12) were treated with middle cerebral artery occlusion. We distinguish cerebral infarction from the color, which is a white unstained area surrounded by red living tissue. Fig.1A is a set of representative experimental results, which are the results obtained after staining for 24 hours after the infarct was permanently occluded with TTC. After treatment with middle cerebral artery occlusion, the infarct area was significantly different in these three mice. The proportion of the infarct region to the total brain volume was 27.1±3.5% in rollingNagoya, 20.2±3.5% in leanermice, and 42.9±4.5% in wild-type mice.

Embodiment 3

[0047] Ca V 2.1α1 gene mutant mice in in vitro ischemia model [Ca 2+ ]i reduction

[0048] To investigate whether the reduction in infarct volume in mutant mice is related to the neuronal calcium pathway, we used hippocampal slices to examine [Ca 2+ ]i changes, OGD treatment can make local ischemia. Ca V The 2.1 channel is strongly expressed in the hippocampus. Before OGD treatment, there was no significant difference in the basal ratio of the pyramidal cell layer in the CA1 region of the three mice (wild type: 0.847±0.011; rollingNagoya: 0.827±0.022; leanermice: 0.803±0.013). Once OGD starts processing, [Ca 2+ ]i appeared increasing, and within 4 minutes after treatment, the normalized index of wild-type mice was much higher than that of the other two groups of mice. The maximum rate of increase was also different among the three mice. The rate of increase was 0.083±0.007 / min (p<0.01) in rollingNagoya, 0.062±0.006 / min (p<0.01) in leanermice, and 0.105±0.008 / min in wild...

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Abstract

The present invention relates to the field of biomedicine, particularly to influence of calcium ion increase rate reducing on the cell death reducing with penumbral region neuron in a CaV2.1 mutant mouse model. The main cause of local ischemia caused by cell death and brain damage is abnormal Ca<2+> ion regulation. According to the present invention, in the experiment, the physiological effect of Cav2.1(P-Q type) in ischemic neuronal injury is researched with two kinds of Cav2.1 channel alpha1 subunit mutant mice (rolling Nagoya mice and leaner mice); the local ischemia experiment results show that the cerebral embolism areas of the two mutant models such as rolling Nagoya mice and leaner mice are significantly reduced compared to wild type mice; the in vitro Ca<2+> imaging research results show that the Ca<2+> concentration increase rates of the two Cav2.1 channel mutant mice are slower than the Ca<2+> concentration increase rates of wild type mice; and all the research results show that the Cav2.1 channel provides the important effects in the Ca<2+> dependent local ischemic model, and a certain prevention and protection effect can be provided if the pathway is blocked.

Description

[0001] Technical field: [0002] The invention relates to the field of biomedicine, in particular to reducing the rate at which calcium ions increase and affecting Ca V 2.1 The extent of reduced cell death in penumbral neurons in the mutant mouse model. [0003] Background technique: [0004] During membrane depolarization, voltage-gated Ca 2+ (Ca V ) channel allows Ca 2+ into the cell. In the nervous system, Ca V Channels play an important role in the regulation of diverse neuronal functions due to intracellular Ca 2+ increase in concentration [1] . Ca V A channel is a complex molecular complex composed of α1, β, α2-δ and γ subunits [2] . The α1 subunit is essential for proper channel function and for determining the fundamental properties of the channel [1] . At presynaptic terminals, there are three major Ca V2 Channel type, Ca V2.1 (P / Q type), Ca V2.2 (N-type) and Ca V2.3 (R type), these three types are widely expressed in the central nervous system [3] and...

Claims

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Application Information

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IPC IPC(8): A61K49/00C12Q1/68
Inventor 田晓丽
Owner 宁波美丽人生医药生物科技发展有限公司
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