[Ca2+] i reduction of CaV2 1 alpha 1 gene mutation mice in in-vitro ischemia model

A technology of α1 subunit and model, applied in the field of biomedicine, can solve problems of different severity

Inactive Publication Date: 2017-05-31
宁波美丽人生医药生物科技发展有限公司
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  • Abstract
  • Description
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  • 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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  • [Ca2+] i reduction of CaV2 1 alpha 1 gene mutation mice in in-vitro ischemia model
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  • [Ca2+] i reduction of CaV2 1 alpha 1 gene mutation mice in in-vitro ischemia model

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Experimental program
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Effect test

Embodiment 1

[0038] Expression pattern of Cav2.1α1 mRNA

[0039] We used in situ hybridization to evaluate the distribution of Cav2.1α1 mRNA in wild-type mice (n=6), rollingNagoya (n=5) and leanermice (n=5); the distribution in the three mice was 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 the expression levels of CaV2.1α1mRNA in the olfactory bulb, cerebral cortex, caudate putamen, hippocampus, cerebellum and liver in these three mice. In the olfactory bulb, cerebral cortex, caudate putamen, hippocampus, and cerebellum of these three mice, the relative expression levels of total CaV2.1α1 were not significantly different (wild-type mice, rolling Nagoya and leaner mice i...

Embodiment 2

[0041] CaV2.1α1 mutant mice have reduced infarct volume in an in vivo ischemia model

[0042]Wild-type mice (n=12), rollingNagoya (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 the 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

[0044] CaV2.1α1 gene mutant mice in in vitro ischemia model [Ca 2+ ]i reduction

[0045] 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 among 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 invention relates to the field of biological medicine, in particular to [Ca2+] i reduction of CaV2.1 alpha 1 gene mutation mice in an in-vitro ischemia model. The primary reason of ischemia caused by cell death and cerebral injury is Ca2+ ionic regulation abnormity. Depolarization of a neuron membrane results in activation of a Ca2+ voltage gating channel and influx of Ca2+. The two Cav2.1 channel alpha 1 subunit mutation mice (rolling Nagoya and leaner mice) are used in an experiment to study a physiological effect of CaV2.1 (P-Q type) in ischemic neuron damage. A result of the ischemia experiment shows that the brain tissue embolism area of the two mutation models, namely the rolling Nagoya and Leaner mice, is obviously reduced as compared with wild mice. In an in-vitro Ca2+ imaging study, an increase rate of the Ca2+ concentration of the two Cav2.1 channel mutation mice is less than that of the wild mice. The study results show that the Cav2.1 channel plays an important role in the Ca2+ dependent ischemia model, and the blocking of the channel can exert a certain prevention and protection effect.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to the reduction of [Ca2+]i in the in vitro ischemia model of CaV2.1α1 gene mutant mice. Background technique [0002] 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 participate in Ca 2+ dependent exocytosis release of neurotransmitters [4] . Give...

Claims

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Application Information

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Patent Type & Authority Applications(China)
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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