Preparation method of a model of synuclein pathological REM sleep behavior disorder

Abstract

The present invention relates to a method for inducing a rapid eye movement sleep behavior disorder (RBD) phenotype that can be converted to a Parkinson's phenotype in a non-human test animal, the method comprising 1) unilateral treatment of the non-human test animal Or bilateral pontine tegmental dorsolateral inferior nucleus (SLD) stereotaxic injection of substances capable of inducing pathological changes in synuclein; 2) Assess the induction of RBD phenotype in the non-human test animals; 3) In the described Induction of Parkinsonian phenotypes was assessed in RBD animals. The invention also relates to a preparation method of a synuclein pathological RBD model. The present invention proposes to inject prefabricated fibrils (PFFs) that can induce synuclein pathology into SLD nuclei in a stereotaxic manner. It is expected that this model can provide an important animal model basis for elucidating the etiology, pathogenesis, and Parkinson's outcome of RBD in future research and developing effective blocking drugs.

Description

technical field [0001] The present invention relates to the fields of medicine and biotechnology. Specifically, the present invention relates to a method for preparing an animal rapid eye movement sleep behavior disorder (RBD) model based on the pathological characteristics of synuclein in the inferior dorsolateral nucleus of the pontine tegmentum (SLD), which can be converted to a Parkinsonian phenotype. Background technique [0002] As an important premotor symptom of Parkinson's disease, rapid eye movement sleep behavior disorder (RBD) can appear as early as 10 years before the onset of motor symptoms [1], and continuous follow-up of primary RBD patients found that the follow-up period was 10-15 years. About 80-90% of patients transform into synucleinopathies [2]. Neuroimaging and autopsy studies of patients with primary RBD also suggest that patients at this stage have reduced striatal dopamine transporter function, loss of midbrain substantia nigra dopaminergic neurons...

AI Technical Summary

Problems solved by technology

[0004] However, many of the existing RBD modeling schemes listed above still have major defects: 1. The mechanical destruction method used in the early stage and the neurotoxin damage method later will inevitably affect the surrounding brain regions and nuclei, introducing many irrelevant The confounding factors of the prediction are difficult to achieve a single variable and precise, nor can it reflect the pathological nature of RBD synucleinopathy; 2. Emerging gene mutations or gene silencing targeting key receptors and transporters in the REM sleep regulation loop Although it can selectively target and manipulate specific types of neurons in specific regions to achieve precision and minimal invasiveness, this modeling method does not involve the participation of synuclein pathological factors, nor can it reflect RBD synuclein disease 3. Whether the above RBD model construction schemes are mechanical damage, toxin damage, or REM loop receptor and transporter gene silencing strategies, without exception, they can induce RBD-like behaviors in animals in a short period of time or even immediately, so they do not Pathophysiological features of a chronic progressive degenerative synucleinopathy inconsistent with RBD

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