40 results about "Striatum" patented technology

The invention relates to a technetium [99mTc]-labeled deuterated tropane derivative and application thereof, and belongs to the technical field of nuclear medicine. The invention provides a technetium [99mTc]-labeled deuterated tropane derivative, which can be specifically combined with a dopamine transporter, and can be used for preparing the technetium [99mTc]-labeled deuterated tropane derivative. The technetium [99mTc]-labeled deuterated tropane derivative has the advantages of good affinity to a dopamine transporter, high radioactive uptake of a target region (striatum) in a brain and high target / background ratio, and has an extremely high application prospect in the aspect of SPECT (Single Photon Emission Computed Tomography) imaging of the dopamine transporter.

Described herein, inter alia, are compositions and methods of use for administering a population of regulatory T (TREG) cells and / or a population of midbrain dopamine (mDA) cells to the brain of a subject (e.g., treating Parkinson's disease and / or reducing immune responses due to acupuncture wounds during cell transplantation).

The invention discloses application of C-176 in preparation of a medicine for treating Parkinson's disease, belongs to the technical field of medicines, and particularly relates to a medicine for treating Parkinson's disease, which comprises C-176 or a pharmaceutical salt thereof. As an STING inhibitor C-176 is adopted as a medicine for treating Parkinson's disease, 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) is utilized to construct an animal model of Parkinson's disease, and animal experiments prove that the expression of STING protein in striatum of a mouse in the model is increased, and the expression of tyrosine hydroxylase (TH) is reduced at the same time. The C-176 can improve the expression level of TH in striatum of a Parkinson model mouse. A behavioral experiment result proves that the C-176 can improve the movement and movement coordination ability of a model mouse and relieve the anxiety behavior of the model mouse.

This application belongs to the field of genetic engineering, and specifically relates to a method for constructing a Parkinson's animal model, a gRNA specifically targeting the Parkin gene, and its applications. By injecting a gene editing system specifically targeting the Parkin gene, the Parkin gene of the recipient animal is edited. After two months of viral expression, pathological features similar to those in the brains of PD patients, such as degeneration and death of dopamine neurons, reduced dopamine synthesis in the striatum, and significant aggregation of a-synuclein, can occur. Compared with the PINK1 gene knockout monkey model using the CRISPR / Cas9 technology, the Parkin gene knockout animal model highly coincides with PD patients in terms of gene mutations and selective degeneration and death characteristics of dopamine neurons, providing a more ideal and important animal model for the pathological mechanism of PD and the development of therapeutic targets.

The present invention relates to a method for treating autism spectrum disorder, a mouse for monitoring autism spectrum disorder, and a method for screening a candidate for preventing or treating autism spectrum disorder. Specifically, according to the present invention, the output signal (or excitation of population) of neurons of the ventrolateral thalamus (VL), the laterodorsal thalamus (LD) or the striatum may be suppressed by introducing a halorhodopsin protein into neurons of the ventrolateral thalamus (VL), the laterodorsal thalamus (LD) or the striatum and then irradiating light to induce hyperpolarization of the halorhodopsin protein. Thus, the present invention has the effect of preventing or treating autism.

The invention discloses a PET (Positron Emission Tomography) image transmembrane state synthesis method based on deep learning, which is suitable for DAT (Dopamine Transporter) imaging, improves the diagnosis accuracy of Parkinson's disease through an advanced image processing technology, and consists of two core parts, namely a 11C-CFT generation model and a PD (Parkinson's Disease) classification model. Wherein the < 11 > C-CFT generation model is responsible for converting an actually scanned < 18 > F-FDG PET image into a < 11 > C-CFT PET image through a cross-modal synthesis technology, and the PD classification model outputs a prediction result by utilizing multi-modal information of the real < 18 > F-FDG PET image and the synthesized < 11 > C-CFT PET image. The method has the advantages that the DAT level of a striatum area of a PD patient is directly reflected through the synthesized 11C-CFT PET image by utilizing the advantages of 11C-CFT PET in dopamine energy system evaluation, an intuitive visual basis is provided for a model diagnosis result, doctors are helped to understand and trust diagnosis decisions of an AI model, resource limitation of 11C-CFT PET imaging is effectively overcome, and the method is suitable for popularization and application. Therefore, the accurate PD automatic diagnosis technology can be implemented in a wider medical environment.

The invention discloses an application of indole-3-pyruvic acid in preparation of an STRIPAK blocking agent interacting with striatum, the inventor accidentally discovers that the indole-3-pyruvic acid (IPyA) is combined with striatum protein (STRN3) of STRIPAK to prevent the STRIPAK from being combined with serine / threonine protein phosphatase (PP2A), so that the structure of the STRIPAK is destroyed, PP2A in the compound is inactivated, and the STRIPAK blocking agent interacts with striatum. According to the present invention, with the application of PP2A, the dephosphorylation of PP2A on a variety of kinases such as AMPK, PI3K and the like on the downstream of PP2A can be weakened, the tumor cell proliferation can be ultimately inhibited, the tumor cell killing ability of killer T cells (CD8 + T cells and Tc) can be enhanced, the treatment effect of the immune checkpoint inhibitor (ICI) in tumor treatment can be improved, and the two have the synergistic effect;

The invention discloses application of an Apob gene in preparation of drugs for relieving depression, and belongs to the technical field of biological medicines. According to the present invention, it is found that the APOB protein of the brain region of the DMS is overexpressed, and the APOB protein has the anti-depression effect; when the Apob gene in the GABA energy neuron of the dorsal medial striatum (DMS) is knocked out, the mouse is correspondingly irritable and susceptible, which indicates that the Apob gene has a positive effect in dealing with depression.

Provided herein are novel methods for delivering recombinant adeno-associated viral (rAAV) particles to the central nervous system of a mammal (e.g., a human). In aspects, the methods involve administering rAAV particles containing a heterologous nucleic acid to the striatum and causing expression of the heterologous nucleic acid in at least the cerebral cortex and the striatum of the mammal.

The application provides application of a hydroxy pentylbenzoic acid double ester compound L-NRB in treatment of Parkinson's disease. Animal model test proves that L-NRB can effectively improve the MPTP-induced Parkinson's disease mouse behavior index, increase the content of DA and its metabolites DOPAC and HVA in the brain, inhibit the loss of dopamine neurons in the substantia nigra and striatum, inhibit the expression of inflammatory factors and the activation of astrocytes and microglia in the substantia nigra; meanwhile, L-NRB can also inhibit the activity of MAO-B in the striatum. L-NRB has no toxic side effects in vivo and in vitro; has the advantages of high safety, small dosage, long-term stability and the like, and is suitable for further development for actual clinical treatment.

The present invention relates to a method for treating autism spectrum disorder, a mouse for monitoring autism spectrum disorder, and a method for screening a candidate for preventing or treating autism spectrum disorder. Specifically, according to the present invention, the output signal (or excitation of population) of neurons of the ventrolateral thalamus (VL), the laterodorsal thalamus (LD) or the striatum may be suppressed by introducing a halorhodopsin protein into neurons of the ventrolateral thalamus (VL), the laterodorsal thalamus (LD) or the striatum and then irradiating light to induce hyperpolarization of the halorhodopsin protein. Thus, the present invention has the effect of preventing or treating autism.

To provide anti-DAT antibodies and compositions thereof for slowing the progression of Parkinson's disease.SOLUTION: Anti-DAT antibodies are formed by transcription and translation of gene fragments containing specific sequences. The anti-DAT antibody provided by the present invention is used for labeling a dopamine transporter. The anti-DAT antibody provided by the present invention is capable of forming a composition that crosses the blood-brain barrier, is capable of specifically binding to dopaminergic neurons, and is capable of specifically binding to cells in the striatum The use of reducing the deposition of α - synuclein protein in the brain region is achieved, and the excellent effect of delaying the progress of Parkinson's disease is exerted.SELECTED DRAWING: Figure 1

The invention relates to an application of bifidobacterium animalis subsp. Lactis BLa80 in preparation of a preparation for improving Parkinson's disease. The bifidobacterium animalis subsp. Lactis BLa80 is a strain of the bifidobacterium animalis subsp. Lactis BLa80 with the preservation number of CGMCC (China General Microbiological Culture Collection Center) No.22547, and the strain of the bifidobacterium animalis subsp. Lactis BLa80 is a strain of the bifidobacterium animalis subsp. Lactis BLa80 with the preservation number of CGMCC No.22547. The brand new application of the BLa80 strain of the animal bifidobacterium subsp. Lactis is developed, namely the BLa80 strain is used for improving the Parkinson's disease, specifically, the BLa80 strain can weaken the cytotoxicity of 6-OHDA induced SH-SY5Y cells, relieve weight loss of MPTP induced subacute Parkinson's disease model mice, relieve dyskinesia of the mice and improve the Parkinson's disease. According to the present invention, the mice are subjected to the mouse striatum activation, such that the dopaminergic neuron is protected, the dopamine content in the mouse striatum is increased, the intestinal inflammation is relieved, the ratio of the thick-wall mycophylum to the bacteroides in the mouse intestinal flora is increased, the intestinal beneficial flora abundance is improved, and the intestinal flora diversity is increased;

Diagnosing and treating presbycusis (age related hearing loss) includes measuring basilar membrane stiffness. In an example, a low frequency component of an electrocochleogram stimulation signal is used to bias a region of the basilar membrane, the results of which are used basilar membrane stiffness. The resulting measurement is used to measure a subcomponent of presbycusis. Further, the measurement can be combined with known diagnostic methods to reveal or distinguish other origins of hearing loss such as strial presbycusis, sensory presbycusis, neural presbycusis, and cochlea conductive presbycusis. The relative contributions for each of the diagnosed origins of hearing loss can be determined.

The invention relates to the technical field of stimulation feedback feature extraction, in particular to a stimulation feedback visual analysis method for a cortex-striatum reward network. The method comprises the following steps: constructing a stimulation propagation path of each simulation stimulation test, and obtaining propagation contribution degrees of nodes in a reward network under each simulation stimulation test; screening an efficient propagation path of each simulation stimulation test according to the propagation contribution degree of the nodes on the stimulation propagation path, adjusting the stimulation increase amount of the nodes in the reward network during the next simulation stimulation test, and recalculating the propagation contribution degree of the nodes in the reward network under the next simulation stimulation test; and performing visual analysis on stimulation feedback according to the propagation contribution degree of the node under all simulation stimulation tests. According to the method, multiple simulation stimulation tests are carried out on the reward network, so that the propagation process of stimulation and feedback is more detailed and dynamic, the accuracy of identifying the pleasant sensation lacking part is improved, and the stimulation feedback visualization effect of the reward network is improved.

The invention discloses application of Trolox in preparation of a medicine for treating neurodevelopment disorder related diseases, and belongs to the technical field of biological medicine. The invention firstly discovers that Trolox has new application of drugs for preventing and / or treating neurodevelopment disorder related diseases; furthermore, the Trolox restores the neural connectivity by repairing the densities of the damaged neuron dendritic spines of the brain hippocampus and / or striatum; abnormal dopaminergic signal channels are corrected, so that expression of key receptors and downstream molecules thereof is recovered to be normal, and therefore, diseases related to neurodevelopment disorders are prevented and / or treated; the neuroprotective effect of Trolox depends on the activation of dopamine D1 and D2 receptor pathways; in addition, the invention discloses the potential of Trolox in the aspect of targeted repair of the core pathology link of the neurodevelopmental disorder for the first time, and a clear candidate compound and an action target are provided for developing a novel medicine for treating the diseases.

Provided herein are novel methods for delivering recombinant adeno-associated viral (rAAV) particles to the central nervous system of a mammal (e.g., a human). In aspects, the methods involve administering rAAV particles containing a heterologous nucleic acid to the striatum and causing expression of the heterologous nucleic acid in at least the cerebral cortex and the striatum of the mammal.

The invention discloses an anti-DAT antibody which is formed by transcription and translation of a fragment gene, and the fragment gene comprises SEQ ID No: 2. The anti-DAT antibody provided by the invention can be prepared into a composition capable of crossing a blood brain barrier, and can achieve specific binding aiming at dopamine nerve cells, and achieve the excellent effects of reducing accumulation of protein synuclein in a striatum brain region of degeneration or lesion of the dopamine nerve cells and delaying the course of Parkinson's disease.

The invention discloses a five-vine tranquilizing decoction for treating Parkinson's disease and a preparation method thereof, the five-vine tranquilizing decoction is composed of main materials and auxiliary materials, the main materials comprise suberect spatholobus stem, wintercreeper, tuber fleeceflower stem, tinospora sinensis merr and uncaria rhynchophylla; the auxiliary materials comprise the following components: radix paeoniae alba and liquorice. Compared with the prior art, according to the strong medicine etiology and pathogenesis of Parkinson's disease, the traditional Chinese medicine composition takes tuber fleeceflower stem, uncaria, suberect spatholobus stem, wintercreeper and tinospora sinensis merr as main medicines, takes white paeony root as an auxiliary medicine and takes liquorice as an auxiliary medicine through strict compatibility and network pharmacology screening, and the seven medicines are combined to achieve the effects of dispelling wind and nourishing yin, balancing qi and blood, regulating qi and blood and dredging two ways. The Zhuang prescription has the effects of improving the dyskinesia symptom, relieving the loss of black matter-striatum dopaminergic neurons, regulating intestinal flora and metabolites of a PD model and promoting the proliferation of regulatory T cells.

The invention belongs to the technical field of medicines, and particularly relates to application of CARNS1 in Parkinson's disease (PD). The research finds that CARNS1 is highly expressed in striatum and nigra brain regions in C57BL / 6 mouse brains, is positioned in dopaminergic neurons in the nigra brain regions, and is down-regulated in MPTP and alpha-syn animal models and MPP + cell models; the nigra region CARNS1 knocks down and aggravates MPTP-induced dyskinesia and neurodegeneration, and the exogenous supplement carnosine can partially reverse phenotypes; the overexpression of the wild type CARNS1 can be used for relieving the neurodegeneration in MPTP and alpha-syn models. The invention clarifies the regulation role of CARNS1 in PD, provides a new perspective for understanding the pathogenesis of PD, and prompts that the CARNS1-carnosine metabolic axis may become an important target for intervening the pathological process of PD.

The invention belongs to the technical field of Parkinson's disease sleep disorder research, and particularly relates to a neural network modeling method for researching Parkinson's disease sleep disorder. Firstly, nucleuses forming the neural network are determined, the nucleuses comprise a cortex, striatum, a globular pallidum outer side, a globular pallidum inner side, a subthalamic nucleus, a thalamus and a foot bridge nucleus, the cortex comprises rCTX and iCTX neurons, and the striatum comprises D1 middle spinous neurons and D2 middle spinous neurons; then, mathematical modeling is carried out on neurons of various nuclei, and membrane potential equations of various neurons are obtained; and finally, performing synaptic connection on neurons, adopting an Alpha synaptic model for synaptic connection between neurons rCTX and D2, between rCTX and iCTX, between iCTX and rCTX, between D1 and GPi, between D2 and GPe, between D1 and D1, between GPe and GPi, between GPe and GPe, between STN and GPi, between GPi and Th, between GPi and PPN, and between Th and rCTX, and adopting a double-index synaptic model for synaptic connection between neurons GPe and STN, between rCTX and STN, between PPN and STN, between STN and GPe, and between STN and PPN. According to the method, the foot bridge nucleus is introduced on the basis of the basal nucleus-thalamus-cortex neural network, the association between the foot bridge nucleus and the sleep disorder is established, and the blank of research on the sleep disorder of the Parkinson's disease is filled.

The present invention is directed to amino and alkyl pyrazolopyrimidine compounds which may be useful as therapeutic agents for the treatment of disorders associated with phosphodiesterase 9 (PDE9). The present invention also relates to the use of such compounds for treating cardiovascular and cerebrovascular diseases, such as hypertension, chronic kidney disease and heart failure, and neurological and psychiatric disorders, such as schizophrenia, psychosis or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.

This invention relates to the field of pharmaceutical technology for treating motor dysfunction in Parkinson's disease, and particularly to a traditional Chinese medicine preparation for treating motor dysfunction in Parkinson's disease. The formula consists of Cimicifuga rhizome, processed turtle shell, Angelica sinensis, raw licorice root, ginger-processed Pinellia ternata, Gastrodia elata, and scorpion. This invention uses a traditional Chinese medicine formula to treat motor dysfunction in Parkinson's disease. The medicinal materials comply with national regulations for the management of traditional Chinese medicine materials and have undergone clinical testing. The formula is rationally formulated with high synergistic effects and long-lasting and stable efficacy. Based on the principles of traditional Chinese medicine syndrome differentiation and treatment, this formula addresses the deficiency of both liver and kidney, and the insufficiency of qi and blood, with tremor and paralysis attributed to internal liver wind. It significantly improves motor dysfunction and tremor symptoms in Parkinson's disease. This preparation is highly effective, safe, reliable, and has few side effects. It can also significantly reduce the expression levels of tyrosine hydroxylase in the substantia nigra and striatum. This preparation represents a new approach to treating motor dysfunction in Parkinson's disease and has broad prospects in the field of treating this condition.

The invention belongs to the field of neurobiology and neuroengineering, and provides a method for predicting and preventing dyskinesia diseases (such as Parkinson's disease) caused by dopamine system damage before clinical symptoms appear by taking abnormal low-frequency beta neural oscillation of a specific brain region as a biomarker. The method is used for predicting abnormal high-frequency beta neural oscillation occurring after the diseases (especially the period after motion symptoms appear); wherein the monitoring and intervention target brain region of the abnormal low-frequency beta oscillation is striatum, and the abnormal high-frequency beta oscillation is visible in the striatum, the motor cortex and the subthalamic nucleus.

To provide medicaments for delivering recombinant adeno-associated virus (rAAV) particles to the central nervous system of a mammal (e.g., a human).SOLUTION: Provided is a medicament containing a recombinant adeno-associated virus (rAAV) particle containing an AAV serotype 2 (AAV2) capsid, which is used for delivering the rAAV particle to a central nervous system of a mammal, the rAAV particle being administered to each hemisphere of a striatum at a rate greater than 1 μL / min to 5 μL / min by convection-enhanced delivery (CED), the rAAV particle comprising an rAAV vector comprising a heterologous nucleic acid encoding a therapeutic polypeptide, and the heterologous nucleic acid being expressed in at least the striatum and at least an occipital cortex and / or layer IV of a cerebral cortex of the mammal.SELECTED DRAWING: None

A specific method for differentiating pluripotent stem cells into midbrain substantia nigra dopaminergic (A9 mDA) neural cells is provided. The differentiation forms mature A9 mDA neurons that express surface molecular markers of midbrain substantia nigra dopaminergic neurons, including TH, FOXA2, EN1, LMX1A, NURR1, and GIRK2, while expressing little of the marker CB for ventral tegmental area dopaminergic neurons. The A9 mDA neural cells are transplanted into the substantia nigra, and their axons specifically project to the target brain region dorsal striatum innervated by endogenous substantia nigra dopaminergic neurons; the transplanted A9 mDA neurons themselves exhibit the classic electrophysiological properties of endogenous substantia nigra dopaminergic neurons, including low frequency of spontaneous firing and sag induced by hyperpolarizing current stimulation. Transplanting A9 mDA neural cells into the substantia nigra or striatum of a subject with a neurodegenerative disease can improve motor dysfunction.

The invention provides application of a glucosylceramide synthetase activator in preparation of a medicine for preventing and / or treating anxiety, and belongs to the field of medicine. According to the application disclosed by the invention, the glucosylceramide synthetase of the dorsal striatum is found to be an important regulatory protein for treating anxiety for the first time, and the key effect of the glucosylceramide synthetase in the dorsal striatum in anxiety mice induced by chronic constraint stress is determined by means of molecules, behavioristics and the like. It is found for the first time that the glucosylceramide synthetase agonist can significantly improve anxiety behaviors induced by chronic constraint stress, and the glucosylceramide synthetase agonist has wide application prospects in preparation of drugs for preventing and / or treating anxiety.

The invention provides a transcranial magnetoacoustic stimulation system based on regulation and control of a cortical-basal node neural circuit. The transcranial magnetoacoustic stimulation system comprises a digital signal generator, a radio frequency power amplifier, an ultrasonic transducer, an oscilloscope, a microelectrode array and two permanent magnets, the digital signal generator is connected with the ultrasonic transducer through the radio frequency power amplifier, and the ultrasonic transducer is provided with a collimator and emits ultrasonic waves in a pulse form; the microelectrode array is arranged on the head of a stimulated object and is used for collecting electroencephalogram signals in real time when stimulation is executed; the permanent magnets are fixed to the two sides of the head of a stimulated object, static magnetic fields and focused ultrasonic stimulation are applied to a target brain area at the same time, and neural activities of the deep brain area are regulated and controlled through the magnetoacoustic coupling effect. According to the application, the magnetoacoustic coupling effect is utilized to perform non-invasive regulation and control on neural activity in the deep brain region, so that the neural oscillation synchronism between the prefrontal lobe and the striatum is enhanced, and the motor and cognitive dysfunction related to the Parkinson's disease is improved.

The invention relates to the technical field of disease model construction, in particular to a construction method of a vascular Parkinson's syndrome composite animal model. The method comprises the following steps: sequentially performing chronic whole-brain hypoperfusion treatment and systemic mitochondrial complex I inhibition treatment on an advanced mammal, and applying the vascular Parkinson's syndrome animal model to preparation of a medicine for screening or evaluating prevention and / or treatment of the vascular Parkinson's syndrome. According to the construction method of the vascular Parkinson's syndrome composite animal model provided by the invention, a stable cerebrovascular lesion and a definite nigra-strike dopamine energy system are simultaneously induced on the same animal individual through an innovative double-strike modeling method; therefore, a brand-new animal model which is highly similar to human diseases in pathology is created.

Provided herein are compositions and methods for treating striatonigral degeneration, and more particularly, to a recombinant adenovirus associated (AAV) vector comprising a nucleic acid comprising in a 5′ to 3′ direction: a 5′ AAV inverted terminal repeat (ITR) sequence, a promoter sequence, a gene encoding a full-length human VAC14 gene, a polyadenylation sequence, and a 3′ ITR sequence.