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Application of inhibitory neural precursor cell to preparation of drug for treating Alzheimer's disease

A neural precursor cell, Alzheimer's disease technology, applied in the field of medicine, to achieve the effect of improving cognitive impairment and maintaining balance

Inactive Publication Date: 2019-03-12
SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, it has not been reported whether MGE-derived neural precursor cells can treat AD.

Method used

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  • Application of inhibitory neural precursor cell to preparation of drug for treating Alzheimer's disease
  • Application of inhibitory neural precursor cell to preparation of drug for treating Alzheimer's disease
  • Application of inhibitory neural precursor cell to preparation of drug for treating Alzheimer's disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Example 1 Obtaining MGE-derived inhibitory neural precursor cells

[0023] This technology uses green fluorescent protein-labeled mice as donors, and the transplanted inhibitory intermediate precursor cells can be visually observed in subsequent experiments. The 13.5-day pregnant EGFP mouse was taken out of the cage, and anesthetized with 3.6% chloral hydrate, 0.01ml / g. After anesthesia, sterilize the whole body with alcohol and put it in an ice box, quickly take out the fetal mouse and put it in 4-degree LiebovitzL-15 medium. After the placenta is peeled off, put the fetal mouse into a new petri dish. Use a new set of tweezers to peel off the scalp, periosteum, and meninges sequentially under a dissecting microscope, and put the brain into another Petri dish. Adjust the field of view, cut and separate the two hemispheres on the sagittal plane, and carefully remove the corpus callosum to see the situation inside the ventricle. There are 3 obvious ganglion protrusions, ...

Embodiment 2

[0024] Example 2: Transplantation of MGE-derived inhibitory neural precursor cells

[0025] This technology uses APP / PS1 mice, the classic model of Alzheimer's disease, and the background is C57BL / 6J. This double-transgenic mouse can express mutant human presenilin 1 (PS1-dE9) and human mouse amyloid precursor protein ( APPswe) fusion, the expression of these two genes are all initiated by the mouse prion protein promoter. The PS1-dE9 mutation in the human presenilin gene results from a deletion of the ninth exon of the gene. The model mice showed obvious cognitive impairment at 6-7 months. In this transplantation protocol, mice were transplanted when they were 7 months old.

[0026] The mice to be transplanted were divided into three groups: the experimental group (APP / PS1+transplanted stem cells), the experimental control group (APP / PS1), and the normal control group (WT littermates), with 15 mice in each group. Mice in the experimental control group and normal control gr...

Embodiment 3

[0028] Example 3: Successful Migration and Differentiation of Transplanted Suppressor Precursor Cells

[0029] Transplanted suppressive precursor cells can survive and migrate well ( figure 1 ) and differentiate into interneurons ( figure 2 ). Three mice were taken 5 days after transplantation for perfusion sections and immunostained with the suppressive stem cell marker LHX6, as shown in figure 2As shown in -A, most of the transplanted GFP-expressing cells are stem cells of inhibitory interneurons. Perfusion sections were performed at 7 days, 30 days and 60 days, and the sections with the same interval of 140um were taken and then immunofluorescent stained to observe the distribution of cells in the hippocampus. As shown in Figure 2-B, from left to right, the cells were continuously sliced ​​at the same interval from the proximal end to the proximal end of the hippocampus. At 7 days, the transplanted cells did not migrate around the injection point, but it could be seen ...

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Abstract

The invention discloses application of an inhibitory neural precursor cell to the preparation of a drug for treating the Alzheimer's disease, and belongs to the technical field of medicines. Accordingto the application, an interneuron deleted in a brain suffered from the AD (Alzheimer's disease) can be more accurately compensated by adopting the transplantation of the inhibitory neural precursorcell from an MGE (Medial Ganglionic Eminence) source; and the balance between the excitability of the brain and an inhibitory neural network is maintained. Compared with an anti-excitability medicine,a stem cell subjected to one-time transplantation can effectively survive and is differentiated into a required inhibitory interneuron, takes effect for a long term, has no side effect of a chemicaldrug, and is high in safety. The inhibitory neuron deleted in the brain suffered from the AD is effectively and accurately compensated through the scheme of transplanting the inhibitory neural precursor cell from the MGE source; and the cognitive disorder of the AD is improved.

Description

technical field [0001] The invention relates to the use of an inhibitory neural precursor cell for preparing a drug for treating Alzheimer's disease, and belongs to the technical field of medicine. Background technique [0002] Alzheimer's disease (AD) is a neurodegenerative disease with three typical pathological features: amyloid senile plaques formed by the deposition of amyloid β (Aβ) in the patient's brain, and hyperphosphorylated Tau protein. neurofibrillary tangles and widespread loss of neurons. The clinical manifestations are memory loss, persistent cognitive decline, and movement disorders, accompanied by a series of psychiatric symptoms. The pathological mechanism of AD is complex. Currently, there are Aβ theory, Tau protein theory, cholinergic nerve abnormality theory, metabolic disorder theory, free radical and apoptosis theory, and genetic inheritance theory. In recent years, the theory of excitatory-inhibitory neural activity imbalance in the AD brain has at...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K35/30A61P25/28
CPCA61K35/30A61K9/0019A61P25/28
Inventor 吕美红马全红陈继博
Owner SUZHOU UNIV
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