Preparation method of synuclein pathological rapid eye movement sleep behavior disorder model

Abstract

The invention relates to a method for inducing a rapid eye movement sleep behavior disorder (RBD) phenotype capable of transforming to a Parkinson phenotype in a non-human subject animal. The method comprises the following steps: 1) stereotactically injecting a substance capable of inducing a pathological change of synuclein into a unilateral or bilateral mesocephalon sublaterodorsal tegmental nucleus (SLD) of a non-human subject animal; 2) evaluating the induction of the RBD phenotype of the non-human tested animal; and 3) evaluating the induction of the Parkinson phenotype in the RBD animal. The invention also relates to a preparation method of a synuclein pathological RBD model. Prefabricated fibrous bodies (PFFs) capable of inducing synuclein pathology is stereodirectionally injected into an SLD nucleus, a mouse RBD model capable of transforming to a Parkinson phenotype is constructed by virtue of a pathology induction characteristic of "dissemination-nucleation" of the fibrous bodies, and the model is expected to provide an important animal model basis for clarification of pathogenesis and Parkinson's disease transforming of RBD and research and development of effective blocking drugs in a future research.

Description

technical field [0001] The invention relates to the fields of medicine and biotechnology. Specifically, the present invention relates to a preparation method of an animal rapid eye movement sleep behavior disorder (RBD) model that can revert to a Parkinsonian phenotype based on the pathological characteristics of synuclein in the subdorsal lateral nucleus of the pontine tegmentum (SLD). 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 patients with primary RBD found that after 10-15 years of follow-up About 80-90% of patients convert to synucleinopathies [2]. Neuroimaging and autopsy studies of patients with primary RBD also suggest that patients at this stage have decreased function of striatal dopamine transporters, loss of dopaminergic neurons in the substantia nigra of the midbrain, sub...

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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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