CN103340859A - Method for establishing non-human primate animal model of parkinson disease by lateral ventricle administration of MPP<+> - Google Patents
Method for establishing non-human primate animal model of parkinson disease by lateral ventricle administration of MPP<+> Download PDFInfo
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- CN103340859A CN103340859A CN2013102190311A CN201310219031A CN103340859A CN 103340859 A CN103340859 A CN 103340859A CN 2013102190311 A CN2013102190311 A CN 2013102190311A CN 201310219031 A CN201310219031 A CN 201310219031A CN 103340859 A CN103340859 A CN 103340859A
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Abstract
A method for establishing a non-human primate animal model of parkinson disease by lateral ventricle administration of MPP<+> belongs to the biomedical technology. The method comprises the following steps: 1, preparing a lateral ventricle administration device; 2, according to a monkey brain atlas and nuclear magnetic resonance imaging data, acquiring a positioning coordinate of a lateral ventricle; 3, inserting a catheter into a lateral ventricle administration position through a monkey stereotaxic instrument, and beginning to administrate the drug after 5-8 days after the animal recovers; injecting a physiological saline solution containing MPP<+> into the lateral ventricle by an injector connected with the tail end of an administration pipe, with the MPP<+> concentration of 0.5-0.7 mg/mL and each administration dosage of 0.1-0.3 mL; carrying out administration one time every 48-72 hours, and after administration for 30-60 days, establishing the non-human primate animal model of the parkinson disease. The method employs a new administration mode that the MPP<+> (1-methyl-4-phenylpyridinium iodide) drug is directly injected into the lateral ventricle of the animal for modeling. With lateral ventricle injection, MPP<+> can perform whole brain circulation together with cerebrospinal fluid to specifically damage dopamine neurons in a brain and cause symptoms of the parkinson disease, and can furthest avoid toxic and side effects of the drug on a periphery.
Description
Technical field
The invention belongs to biomedical technology, be specifically related to the method for building up of animal model.
Background technology
Non-human primate is (as macaque for many years, food Eriocheir sinensis time etc.) be the desirable object of setting up animal model for parkinsonism, modeling method commonly used mainly is to utilize MPTP(1-methyl-4-phenyl-1,2,3, the 6-tetrahydropyridine) intravenous drip, the means of intramuscular injection or the disposable administration of carotid artery are set up chronic or acute animal model for parkinsonism.Though these methods can induce typical parkinson disease behavior symptom, have tangible drawback.M. sum up in one piece of summary about the parkinson animal model that Gerlach and P. Riederer deliver following some: the animal during the modeling shows bigger individual variation, animal need be born drug-induced toxic and side effects and behavior symptom instability, and (M. Gerlach ﹠amp such as recovery are in various degree arranged after drug withdrawal; P. Riederer. Animal models of Parkinson's disease:an empirical comparison with the phenomenology of the disease in man. J Neural Transm (1996) 103:987-1041).
MPP
+(1-methyl-4-phenylpyridinium ion) is the oxidation product of MPTP, also is specificity damage dopamine neuron and cause Parkinsonian major incentive (summary of two pieces of classics has been thoroughly discussed MPTP and MPP
+Toxicological effect: Susan Duty ﹠amp; Peter Jenner. Animal models of Parkinson ' s disease:a source of novel treatments and clues to the cause of the disease. British Journal of Pharmacology (2011) 164 1357 – 1391; Fabio Blandini ﹠amp; Marie-Therese Armentero. Animal models of Parkinson ' s disease. FEBS Journal 279 (2012) 1156 – 1166).Because MPP
+Can not see through blood brain barrier, so traditional medication is difficult to MPP
+Send in the central nervous system.
Summary of the invention
The objective of the invention is to overcome the shortcoming that prior art exists, a kind of tricorn MPP is provided
+The method of non-human primates animal model for parkinsonism is set up in administration, require this animal model basic physiological in order, behavior symptom typical case, modeling cycle be shorter.
The inventive method is carried out according to the following steps:
1, make the tricorn doser, this device includes a stainless steel pipe, a rustless steel delivery tube that can in conduit, move freely, and a plug that the conduit mouth of pipe can be clogged, catheter diameter is 0.5～0.6mm, length is 32～38mm.The length of delivery tube preferably surpasses catheter length 0.5～1.0mm.
2, obtain the elements of a fix of tricorn according to monkey brain collection of illustrative plates and nmr imaging data.Preferentially choosing bigger site, tricorn zone is the administration position.
3, with conduit through ventricles of the brain administration position, monkey stereotaxic instrument inserting side, visible cerebrospinal fluid is obviously gushed out, and fixes conduit with dens supporter cement and skull titanium screw then, and clogs the mouth of pipe of conduit with plug, treats that the animal recovery began administration after 5～8 days.Extract plug during each administration, insert delivery tube, with MPP
+Normal saline solution is by injecting in the tricorn MPP with the terminal syringe that links to each other of delivery tube
+Concentration be 0.5-0.7mg/mL, each administration 0.1-0.3mL extracts delivery tube and inserts plug and sterilization after the administration.Be administered once every 48-72 hour, just can set up the non-human primates animal model for parkinsonism in administration 30-60 days.MPP
+Concentration, each dosage, delivery time in above-mentioned scope, adjust variation according to different experiment needs.
What need spell out is: the inventive method of above-mentioned steps record is not diagnosis or the Therapeutic Method of disease, but the method for building up of animal model; This method does not comprise any diagnosis algorithm or detects step.This method neither non-therapeutic purposes surgical method.This method is the technical scheme that can use in the biomedical technology industry, be meet the natural law, the feature that possesses skills, enforceable technical scheme.The enforcement of this method has repeatability, and the technical staff of field of biomedicine technology can repeat the inventive method that implement to adopt for the technical solution problem in the patent application, the above-mentioned steps record.
Beneficial effect of the present invention: adopted new mode of administration, namely directly with medicine MPP
+(1-methyl-4-phenylpyridinium ion) is expelled to the interior modeling of tricorn of animal.MPP
+Can damage dopamine neuron and initiation parkinson disease symptom in the brain specifically with the full cerebral circulation of cerebrospinal fluid by intracerebroventricular injection, and can avoid medicine to the toxic and side effects of periphery to greatest extent.The non-human primates parkinson animal model of Jian Liing has behavior symptom typical case, basic physiological in order and the relative features of smaller of individual variation in this way.This method is convenient to operation, can easily induce the different parkinson animal model of degrees of symptoms by adjusting drug dose with administration frequency, can satisfy different experiment needs.The present invention is a kind of practical new method of setting up the non-human primates animal model for parkinsonism.
The specific embodiment
Embodiment 1: macaque is male, 7 years old.MPP
+Purchase is from U.S. Sigma company.
Stainless steel pipe internal diameter in the tricorn doser is 0.5mm, and length is 35mm.The length of rustless steel delivery tube is 35.5mm.
The elements of a fix according to monkey brain collection of illustrative plates and nmr imaging data acquisition tricorn.The tricorn elements of a fix are: 1mm before the AP0,9.6mm is opened on the side, 22-26mm under the skull.During by above-mentioned coordinate setting, if going into to see behind the brain certain depth limpid cerebrospinal fluid, constantly gushes out from the mouth of pipe by conduit, as can be known the end of the conduit approaching side ventricles of the brain.Fix conduit with dens supporter cement and skull titanium screw then, and clog the mouth of pipe of conduit with the rustless steel plug, treat that animal recovers to begin administration after 8 days, extract plug during each administration, insert delivery tube, with MPP
+Normal saline solution is by injecting in the tricorn MPP with the terminal syringe that links to each other of delivery tube
+Concentration be 0.6mg/mL, each administration 0.2mL extracts delivery tube and inserts plug and sterilization after the administration.Be administered once every 48 hours, the rhesus macaque chronic Parkinson disease animal model was just successfully set up in administration in 45 days.
If with tyrosine hydroxylase immunohistochemistry technology the black substance that the becomes the mould animal visible nigral dopaminergic neuron unit that dyes is obviously lost, meets Parkinsonian pathology variation.This animal model basic physiological in order, the behavior symptom typical case.
Embodiment 2: machin is male, 7 years old.The machin tricorn elements of a fix are: 21-25mm before the AP0,1.2-1.8mm is opened on the side, 15-20mm under the skull.During by above-mentioned coordinate setting, if going into to see behind the brain certain depth limpid cerebrospinal fluid, constantly gushes out from the mouth of pipe by conduit, as can be known the end of the conduit approaching side ventricles of the brain.Fix conduit with dens supporter cement and skull titanium screw then, and clog the mouth of pipe of conduit with the rustless steel plug, recover to begin administration after the week, extract plug during each administration, insert delivery tube, with MPP
+Normal saline solution is by injecting in the tricorn MPP with the terminal syringe that links to each other of delivery tube
+Concentration be 0.7mg/mL, each administration 0.25mL extracts delivery tube and inserts plug and sterilization after the administration.Be administered once every 72 hours, machin chronic Parkinson disease animal model was just successfully set up in administration in 55 days.
If with tyrosine hydroxylase immunohistochemistry technology the black substance that the becomes the mould animal visible nigral dopaminergic neuron unit that dyes is obviously lost, meets Parkinsonian pathology variation.This animal model basic physiological in order, the behavior symptom typical case.
Claims (2)
1. tricorn MPP
+The method of non-human primates animal model for parkinsonism is set up in administration, it is characterized in that carrying out according to the following steps:
(1), make the tricorn doser, this device includes a stainless steel pipe, a rustless steel delivery tube that can move freely in conduit, a plug that the conduit mouth of pipe can be clogged, catheter diameter are that 0.5～0.6mm, length are 32～38mm;
(2), obtain the elements of a fix of tricorn according to monkey brain collection of illustrative plates and nmr imaging data;
(3), with conduit through ventricles of the brain administration position, monkey stereotaxic instrument inserting side, as seen cerebrospinal fluid is obviously gushed out, fix conduit with dens supporter cement and skull titanium screw then, and clog the mouth of pipe of conduit with plug, treat that animal recovers to begin administration after 5～8 days, extract plug during each administration, insert delivery tube, with MPP
+Normal saline solution is by injecting in the tricorn MPP with the terminal syringe that links to each other of delivery tube
+Concentration be 0.5-0.7mg/mL, each administration 0.1-0.3mL extracts delivery tube and inserts plug and sterilization after the administration, be administered once every 48-72 hour, just can set up the non-human primates animal model for parkinsonism in administration 30-60 days.
2. as the said tricorn MPP of claim 1
+The method of non-human primates animal model for parkinsonism is set up in administration, it is characterized in that the length of delivery tube in the tricorn doser surpasses catheter length 0.5～1.0mm.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110327132A (en) * | 2019-08-19 | 2019-10-15 | 四川农业大学 | A kind of easy sturgeon telocoele medication |
| CN111304252A (en) * | 2018-12-10 | 2020-06-19 | 中国科学院昆明动物研究所 | Method for gene editing by injecting virus into specific brain region of animal based on non-therapeutic purpose of PINK1 and PARK7 |
| CN114600831A (en) * | 2022-03-25 | 2022-06-10 | 广西大学 | Construction method of Parkinson disease cynomolgus monkey model |
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| CN1741802A (en) * | 2002-11-21 | 2006-03-01 | 特瓦制药工业有限公司 | Propargyl-trifluoromethoxy-amino-benzothiazole derivatives |
| CN102631234A (en) * | 2012-04-10 | 2012-08-15 | 中国科学院昆明动物研究所 | Deep cerebral dura mater perforating device |
| CN102652682A (en) * | 2012-04-16 | 2012-09-05 | 中国科学院昆明动物研究所 | Micro brain-tissue sampler |
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2013
- 2013-06-04 CN CN2013102190311A patent/CN103340859A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1741802A (en) * | 2002-11-21 | 2006-03-01 | 特瓦制药工业有限公司 | Propargyl-trifluoromethoxy-amino-benzothiazole derivatives |
| CN102631234A (en) * | 2012-04-10 | 2012-08-15 | 中国科学院昆明动物研究所 | Deep cerebral dura mater perforating device |
| CN102652682A (en) * | 2012-04-16 | 2012-09-05 | 中国科学院昆明动物研究所 | Micro brain-tissue sampler |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111304252A (en) * | 2018-12-10 | 2020-06-19 | 中国科学院昆明动物研究所 | Method for gene editing by injecting virus into specific brain region of animal based on non-therapeutic purpose of PINK1 and PARK7 |
| CN111304252B (en) * | 2018-12-10 | 2024-03-01 | 中国科学院昆明动物研究所 | Method for injecting virus into specific brain region of animal for gene editing based on non-therapeutic purpose of PINK1 and PARK7 |
| CN110327132A (en) * | 2019-08-19 | 2019-10-15 | 四川农业大学 | A kind of easy sturgeon telocoele medication |
| CN114600831A (en) * | 2022-03-25 | 2022-06-10 | 广西大学 | Construction method of Parkinson disease cynomolgus monkey model |
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Application publication date: 20131009 |