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Novel growth/neurotrophic factor composition for inducing mature neuron division in vivo and purpose thereof

A technology of nerve growth factor and growth factor, which is applied in the direction of drug combination, nervous system diseases, organic active ingredients, etc., and can solve problems such as low enough to compensate neurons

Active Publication Date: 2018-01-19
INST OF BASIC MEDICAL SCI ACAD OF MILITARY MEDICAL SCI OF PLA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although there is a certain level of neurogenesis in the brain, its level is too low to compensate for the loss of neurons. On the other hand, although neural precursor cells can migrate under certain conditions and differentiate into neurons at specific sites, their Difficult to exploit to prevent aging and treat neurodegenerative diseases 7 , is not enough to reverse the above situation

Method used

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  • Novel growth/neurotrophic factor composition for inducing mature neuron division in vivo and purpose thereof
  • Novel growth/neurotrophic factor composition for inducing mature neuron division in vivo and purpose thereof
  • Novel growth/neurotrophic factor composition for inducing mature neuron division in vivo and purpose thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0062] Example 1: Induction of dividing neurons in the adult rat cerebral cortex

[0063] The present inventors combined (n=3) or did not contain (n=3) fibrin (fibrin) matrix (12.5IU / ml fibrinogen and 12.5IU / ml plasminogen, Sigma F6755 and T5772) of the present invention Compositions (growth factor / neurotrophic factor combination + T3) were injected into the cerebral cortex of adult rats respectively. Wherein, the growth factor / neurotrophic factor combination is composed of the following: EGF (Sigma E4127Lot: SLBJ4118V), bFGF (Invitrogen PMG0033, Lot 489821E), HGF (Millipore Cat: 375228-5UG, Lot: D00165582), IGF (Millipore GF306Lot :2576396), NGF (extracted from mouse submandibular gland, kindly provided by Prof.Shao N) and BDNF. There was no difference in the number of dividing neurons observed between the two groups. Therefore, the growth factor / neurotrophic factor combination + T3 was chosen for subsequent experiments.

[0064] The inventors observed that by microdialysi...

Embodiment 2

[0070] Example 2: Spinal Cord Projection

[0071] In order to identify whether the split-induced neurons in the V layer of the cerebral cortex project to the spinal cord, the inventors injected 3kDa Texas red-dextran amine (TRDA) into the cortex on both sides of the C5 segment in advance. in the spinal cord. In the first week after TRDA injection, dense TRDA-tracked nerve fibers in the C3 spinal cord tract were observed. However, with the prolongation of survival time, the fluorescence intensity gradually became lower and was not observed 14 days after retrograde tracing. This suggests that at the injection site, the regenerated fibers (if any) do not absorb TRDA.

[0072] Then, the composition of the present invention was injected into the M1 region of the cerebral cortex of rats that had received TRDA injection for 4 or 8 weeks, and then the animals were maintained for another 2 days before labeling brain and spinal cord sections with Hoechst and anti-MAP2 antibodies. suc...

Embodiment 3

[0074] Example 3: Inducing the fate of dividing neurons

[0075] To examine the survival of post-mitotic neurons, the inventors injected the growth factor / neurotrophic factor combination + T3 into the cerebral cortex M1 together with BrdU intraperitoneally, administered 3 times within 36 hours to avoid triggering endogenous neural precursors cell. Animals were continued for 4 or 8 weeks. The results showed that all BrdU + / NeuN + Neurons were distributed within a 2 mm diameter of the cylindrical area around the injection needle in the cerebral cortex. Compared to animals sacrificed immediately after induction, in BrdU + NeuN expression was significantly restored in neurons (see Figure 4 ). From the morphology point of view, BrdU + / NeuN + Neurons can be divided into four types: multipolar neurons ( Figure 4 a-d), bipolar neurons ( Figure 4 e-h), pyramidal cells ( Figure 4 i-l) and large neurons ( Figure 4 m-s).

[0076] In the 4-week group, BrdU + / NeuN + T...

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Abstract

The invention relates to a composition for inducing mature neuron division and a purpose thereof, in particular to the composition for inducing the mature neuron division. The composition contains EGFs (Epidermal Growth Factors), bFGFs (basic Fibroblast Growth Factors), HGFs (Hepatocyte Growth Factors), IGFs (Insulin-Like Growth Factors), NGFs (Nerve Growth Factors), BDNFs (Brain-Derived Neurotrophic Factors) and T3 (tri-iodothyronine).

Description

technical field [0001] The present invention relates to a novel growth / neurotrophic factor composition and use thereof for inducing in vivo division of intrinsic mature neurons of the cortex. Specifically, the present invention relates to a composition for inducing the division of mature neurons, comprising: epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), insulin-like growth factor (IGF), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and triiodothyronine (tri-iodothyronine, T3). Background technique [0002] For decades, there has been extensive debate in the academic community about whether neurogenesis occurs in the cerebral cortex of the adult animal brain or whether mature neurons in the cerebral cortex can be induced to divide. It has been previously reported that in adult rodents 1,2 and macaques 3,4 Low levels of neurogenesis are present in the cortex of the brain, but other studies have re...

Claims

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Application Information

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IPC IPC(8): C12N5/0793A61K38/18A61K31/198A61P25/28A61P25/16A61P25/00A61P3/10
Inventor 刘少君刘若虚林世德马洁景书谦
Owner INST OF BASIC MEDICAL SCI ACAD OF MILITARY MEDICAL SCI OF PLA
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