50 results about "GABAergic neuron" patented technology

The invention discloses a Parkinson's disease animal model, a construction method and application, and relates to the field of animal genetic engineering and disease model construction. According to the model, seven mutation sites related to the human familial Parkinson's disease are introduced behind an initiation codon of a fourth exon of an endogenous SNCA gene, and the mutation sites are A18T, A29S, A30P, E46K, H50Q, G51D and A53T and have genotypes related to the human familial Parkinson's disease. The pig model shows nigra dopaminergic neuron reduction and cortical neuron reduction in the newborn period, and the core pathological process of the human Parkinson's disease can be systematically reproduced. The model can be widely applied to Parkinson's disease pathogenesis research, drug screening and cell therapy effect evaluation, and has important scientific research and preclinical application values.

The invention discloses a composition for regulating sleep rhythm homeostasis as well as a preparation method and application thereof. The composition for regulating the sleep rhythm homeostasis is prepared from the following components in percentage by weight: 5 to 18 percent of polydextrose, 9 to 15 percent of galactooligosaccharide, 1 to 10 percent of inulin, 0.4 to 2 percent of gamma-aminobutyric acid, 0.8 to 2.2 percent of L-theanine, 0.1 to 3.5 percent of magnesium citrate, 2 to 21 percent of semen ziziphi spinosae extract, 1 to 10 percent of poria cocos extract, 0.5 to 2 percent of pericarpium citri reticulatae extract, 0.3 to 1 percent of liquorice root extract and 15 to 40 percent of maltodextrin. 5-18% of coconut oil powder MCTs, and 0.5-2% of a lily extract. According to the application, a magnesium MCTs shell-core structure is delivered by maltodextrin to form a mitochondrial piezoelectric engine so as to improve prebiotics, promote flora metabolism efficiency and energy supply feedback, activate intestinal pheochromophilic cells and improve SLC6A4 gene expression so as to improve synthesis of 5-hydroxytryptamine in the brain and activate GABA energy neurons; meanwhile, through the spina date seed and poria cocos quantum dots and a pericarpium citri reticulatae and liquorice pi-pi stacking network, the blood-brain barrier penetration rate is greatly increased, and hypothalamic CRH release is adjusted.

The invention provides a pharmaceutical composition containing polypeptide and application of the pharmaceutical composition to preparation of a medicine for preventing and treating Parkinson's disease, and belongs to the technical field of polypeptide and biology. The amino acid sequence of the polypeptide is PCVLYDLREKM, the damage of 6-OHDA induced BZ555 nematode dopaminergic neurons can be obviously relieved, mouse dyskinesia caused by a Parkinson's disease model can be obviously improved, the spontaneous standing frequency can be improved, the movement speed in an open field can be increased, and meanwhile the IL-1beta and IL-18 levels caused by the mouse Parkinson's disease model can be reduced; the polypeptide provided by the invention can significantly reduce MAO-B level while significantly increasing DA level in nigra of brain tissues of rats with Parkinson's disease, which prompts that the polypeptide provided by the invention has a significant therapeutic effect on Parkinson's disease, and has a wide market prospect in many fields such as health food and medicine.

The present disclosure provides methods of differentiating pluripotent stem cells, including inducible pluripotent stem cells, into lineage-specific midbrain floor progenitor cells, decisive dopaminergic neuron progenitor cells, definitive dopaminergic neuron progenitor cells, and / or dopaminergic neuron cells. Also provided are compositions use thereof, such as for the treatment of neurodegenerative diseases and conditions, including Parkinson's disease, as well as articles of manufacture and kits for use thereof.

A method and system for differentiating acute and chronic pain based on the functional state of specific neural circuits is proposed. This method utilizes in vivo two-photon / endoscopic calcium imaging and ex vivo brain slice patch-clamp techniques to longitudinally monitor the activity dynamics of neurons in the DRN and ZI brain regions during the acute and chronic phases of a neuropathic pain model. By extracting and analyzing calcium and electrophysiological signal parameter sets, distinguishing criteria are established: if the activity of 5-HTergic neurons in the DRN is specifically enhanced in the acute phase, the indication is acute pain; if the activity of GABAergic neurons in the ZI is specifically enhanced in the chronic phase, the indication is chronic pain. This invention achieves an objective and precise differentiation of the transition from acute to chronic pain at the level of specific neural circuits, providing a new strategy and tool for pain mechanism research and clinical diagnosis and treatment.

The invention relates to the technical field of sleep regulation and control, and discloses a method for regulating and controlling anxiety insomnia based on LPAG brain region GABAergic neurons, which takes the regulation effect of LPAG on sleep-awakening as an entry point, adopts in-vivo multichannel recording, EEG / EMG polysleep synchronous recording, photoelectrode recording and opto-genetics manipulation on a cell-loop level, and realizes the regulation and control of anxiety insomnia. The system analyzes the effect of the LPAG in sleep-awakening, and proves the regulation effect of the LPAG on anxiety sleep disorder.

This invention belongs to the field of biomedicine and relates to a method for preparing a Kabuki syndrome brain organoid model and its application. This invention provides the application of GSK-3 inhibitors in the preparation of drugs for treating Kabuki syndrome. Currently existing Kabuki models include heterozygous mice, zebrafish, and 2D human cell models. However, the complexity of human brain development cannot be compared to animal models or single 2D cell models. In this invention, the inventors used CRISPR-CAS9 gene editing technology to knock out KMT2D and established a Kabuki syndrome brain organoid model using brain organoid technology. Studies have found that, compared to the wild type, the Kabuki syndrome brain organoid exhibits premature differentiation of excessive GABAergic neurons. Furthermore, by testing the dosage and time window of the small molecule chir99021, we found that this small molecule can restore the phenotype of abnormal neuronal differentiation in the Kabuki syndrome brain organoid. This discovery will provide new insights for the treatment of Kabuki syndrome.

Provided is a method for differentiating pluripotent stem cells in vitro to prepare a cell population mainly composed of midbrain floor plate dopaminergic progenitor cells, wherein the progenitor cells can efficiently and directionally differentiate into midbrain dopaminergic neuron precursors and midbrain dopaminergic neurons after being transplanted into a subject. Further provided is a cell population prepared by the method, a pharmaceutical composition containing the cell population, and a method for using the cell population or the pharmaceutical composition to treat or ameliorate a neurological disorder caused by a reduction in the number of midbrain dopaminergic neurons and / or impairment of function thereof.

The present invention provides novel irisin peptides (e.g, irisin glycosylation mutants and biologically active fragments thereof). Also provided are methods for preventing or reducing degeneration of dopaminergic neurons and / or preventing or ameliorating at least one motor deficit in a subject in need thereof, such as in a subject with α-synucleinopathy, using the novel irisin peptides to modulate irisin-induced integrin signaling. The novel irisin peptides can also be used in methods for increasing expression of brain-derived neurotrophic factor (BDNF), and / or treating or preventing neurological diseases or disorders that would benefit from decreased neuronal cell death and / or increased neuronal survival in a subject. In addition, the novel irisin peptides may be used in methods for preventing or treating muscular atrophy or muscular dystrophy.

A cell population comprising Corin- and / or Lrtm1-positive cells was produced by the following steps (1) and (2), from which Corin positive and / or Lrtm1 positive cells are collected using a substance that binds to Corin and / or a substance that binds to Lrtm1, and dopaminergic neuron progenitor cells are produced by performing suspension culture of the Corin positive and / or Lrtm1 positive cells in a culture solution containing one or more nutritional factors:(1) a step of performing adhesion culture of pluripotent stem cells in a medium for maintaining undifferentiated state containing a Sonic hedgehog (SHH) signal stimulant, and an undifferentiated state-maintaining factor in the absence of feeder cells but in the presence of an extracellular matrix, and(2) a step of culturing the cell population obtained in the step (1) in a culture solution containing one or more differentiation-inducing factors.

The invention provides an induction method for directionally differentiating neural stem cells into dopaminergic neurons. The induction method comprises the following steps: (1) electroporating the neural stem cells, and enabling a 40-80nm Fe2O3 (at) TGA (at) MIL-100 (at) PDA (at) Ag nano material to enter the neural stem cells; and (2) placing the neural stem cells in the step (1) in a 0.25-0.4 Tesla magnetic field, rotating the neural stem cells in the horizontal direction for 10-20 minutes without changing the magnetic field intensity, then culturing the neural stem cells, controlling the induced electromotive force induced by the rotating magnetic field to be 0.1-10 mV, rotating the magnetic field direction for 10-20 minutes every 23-25 hours, and culturing the neural stem cells for 72-240 hours. According to the induction method, the dopaminergic neuron differentiation rate is high, the synaptic function maturity is improved, the dopaminergic neuron differentiation rate exceeds 80%, the synaptic function maturity is improved compared with a traditional method, the induction method can be applied to Parkinson's disease treatment and nervous system injury repair, and an efficient induction technology is provided for cell treatment of nervous system degenerative diseases and injuries.

The invention provides a plant-derived active polypeptide and application thereof in prevention or treatment of Parkinson's syndrome, and belongs to the technical field of polypeptide bioengineering. The amino acid sequence of the active polypeptide is MKGASSIMYALG, and the active polypeptide is prepared from Fuding white tea raw materials through a directional two-step enzymolysis process. According to the polypeptide, the damage of 6-OHDA induced BZ555 nematode dopaminergic neurons can be remarkably reduced, and the dyskinesia of Parkinson's syndrome model animals can be remarkably improved; meanwhile, the expression level of proinflammatory factors such as IL-1beta and IL-18 in serum of a model mouse can be lowered, the content of dopamine in a nigra area of brain tissue of the model mouse can be increased, and the activity of monoamine oxidase B can be reduced. The results show that the Fuding white tea-derived active polypeptide has exact prevention and treatment effects on Parkinson's syndrome, and has important development value and wide application prospects in the field of medicines.

This invention discloses the application of GRP94 protein as a drug delivery target in the construction of drug carriers for Parkinson's disease. GRP94 is highly upregulated on the cell membranes of dopaminergic neurons in the substantia nigra of Parkinson's disease cells, while its expression is extremely low on the surface of normal brain cells. The invention also discloses the application of GRP94 as a target in a targeted delivery system for anti-Parkinson's disease drugs. By targeting GRP94, the delivered anti-Parkinson's drug can efficiently penetrate the blood-brain barrier to reach the brain parenchyma, avoiding normal brain cells and specifically targeting dopaminergic neurons in the substantia nigra of Parkinson's disease cells, thus achieving targeted drug delivery for Parkinson's disease. This invention applies GRP94 as a target in the construction of drug carriers for Parkinson's disease and in the preparation of targeted delivery systems for anti-Parkinson's disease drugs. Compared to other target receptors that cross the blood-brain barrier for targeted brain delivery, targeting GRP94 more specifically targets dopaminergic neurons in the substantia nigra, avoiding drug accumulation and neurotoxicity in normal intracranial regions.

The invention provides a neural stem cell induced differentiation and clinical application method for intractable epilepsy, and relates to the technical field of biological medicine, the induced differentiation method comprises the following steps: S1, cell source and preparation: adopting induced pluripotent stem cells from a patient; s2, constructing an induced differentiation system, differentiating the induced pluripotent stem cells into GABA (gamma-aminobutyric acid) inhibitory interneurons, and differentiating the GABA inhibitory interneurons; s3, purifying and amplifying the cells, adopting immunomagnetic bead sorting, and purifying and enriching the cells expressing the GABA energy neuron marker; s4, cell quality control; according to the method, the autologous induced pluripotent stem cells of the patient are taken as a source, immunological rejection is avoided, the transplanting safety is improved, and moreover, the high-purity GABAergic neurons can more effectively supplement damaged inhibitory neurons in the brain of the epileptic and reconstruct the inhibition balance of a neural network, so that the epileptic seizure is more effectively controlled.

This invention discloses a method for inducing adipose-derived stem cells to differentiate into dopaminergic neurons, belonging to the field of biomedical technology. Through the isolation, passage culture, and induced transformation of adipose-derived stem cells, dopaminergic neurons are obtained. This method achieves the separation and culture of a large number of adipose-derived stem cells from autologous adipose tissue. By using two specific culture media to transform the adipose-derived stem cells into dopaminergic neurons, a safe and effective batch of stable dopaminergic neurons with a high differentiation rate can be obtained. Immunofluorescence and cell counting experiments show that the dopaminergic neuron conversion rate is 90.4±0.76, and the survival rate is 98.9±0.55. The average dopamine secretion of the transformed dopaminergic neurons, detected by a dopamine ELISA kit, is 450 pg / ml. Therefore, this invention confirms that the adipose-derived stem cell extraction and transformation steps provided by this invention are mild and stable, and the extracted cells are suitable for large-scale applications.

The invention discloses ultrasonic response ZnS (at) Lf piezoelectric nanoparticles as well as a preparation method and application thereof, and relates to the technical field of piezoelectric materials. The ultrasonic response ZnS (at) Lf piezoelectric nano-particle comprises a ZnS nano-particle and lactoferrin loaded on the surface of the ZnS nano-particle. According to the invention, lactoferrin is used as a potent brain-targeting ligand, and passes through a blood-brain barrier to be accumulated in brain parenchyma under the cell transfer action of brain capillary endothelial cells. ZnS nano particles release charges under the ultrasonic action, an electric signal activates a voltage-gated calcium ion channel and extracellular calcium ion influx, calcium ion / calmodulin kinase induces tyrosine hydroxylase (TH) phosphorylation, the activity of tyrosine hydroxylase is enhanced, tyrosine hydroxylase is a key enzyme for generating dopamine, and the activity of the tyrosine hydroxylase is enhanced. Therefore, more tyrosine in vivo is converted into neurotransmitter dopamine under the action of the enzyme. Finally, the regeneration of dopaminergic neurons is realized, so that the Parkinson's disease is effectively improved.

The present application belongs to the technical field of biological medicine, and particularly relates to a pharmaceutical composition for treating Parkinson syndrome. Researches show that the Antarctic fish protein and the multi-domain derivative thereof have the functions of reducing PD pathology and protecting dopaminergic neurons.

Compositions and methods for treating Parkinson's disease are provided. The present specification provides compounds, compositions, uses, and methods for increasing cell viability of dopaminergic neurons or for preventing or treating the death of dopaminergic neurons. In certain embodiments, methods are provided for alleviating symptoms and / or preventing or treating Parkinson's disease in an individual in need thereof, the methods comprising increasing GDP-bound Rab1a (Rab1a GDP ), Rab1a GDP The method includes treating with one or more expressible nucleic acids encoding the compound of formula (I), or a combination thereof.

The invention provides an efficient and repeatable in-vitro differentiation protocol, and human pluripotent stem cells are differentiated into functional midbrain dopaminergic neurons by accurately controlling sequential activation of SHH and FGF8 signal pathways. The protocol comprises five key differentiation stages: neural precursor induction, midbrain mode establishment, midbrain dopaminergic precursor amplification, terminal differentiation and maturation. Experiments prove that after the midbrain dopaminergic neuron obtained by the method is transplanted into a Parkinson's disease model animal body, the survival rate exceeds 80%, and the midbrain dopaminergic neuron can be effectively integrated into a host neural network and improve dyskinesia. According to the differentiation scheme, the purity (gt; gt) of mDA neurons is remarkably improved; 85%) and functional maturity, and a reliable cell source is provided for cell replacement treatment of Parkinson's disease.

This invention discloses the application of bimatoprost in the preparation of drugs for the prevention and / or treatment of Parkinson's disease, within the field of drug reuse. Bimatoprost is a prostaglandin F2α analog, currently mainly used for glaucoma and eyelash growth. This invention has found that bimatoprost can improve Parkinson's disease-related behavioral disorders, increase the expression of tyrosine hydroxylase, a protein associated with dopaminergic neurons in the substantia nigra, and reduce the abnormal accumulation of α-synuclein, thus exhibiting good ameliorative and protective effects against Parkinson's disease. This invention provides a new drug option for the treatment of Parkinson's disease.

The present invention relates to a method for modulating the effect of a botulinum neurotoxin composition, that is accelerating the onset of action and / or extending the duration of action and / or enhancing the intensity of action of a botulinum neurotoxin composition, comprising adding at least one postsynaptic inhibitor of cholinergic neuronal transmission to the botulinum neurotoxin composition. The invention also relates to compositions comprising at least one postsynaptic inhibitor of cholinergic neuronal transmission and a botulinum neurotoxin, and their uses for treating aesthetic or therapeutic conditions.

The application discloses application of anterior piriform cortex GABAergic neurons as an analgesic target point, and relates to the technical field of neuroscience and pain. GABA The application discloses that the neural loop (APC GABA →MD) from the anterior piriform cortex GABAergic neurons to the thalamic dorsal medial nucleus plays a key role in pain regulation. Experiments prove that the loop can not only relieve acute pain, but also has a significant analgesic effect on the clinical treatment of intractable chronic inflammatory pain and neuropathic pain models, and shows a wide treatment application prospect.

Artificial expression constructs are provided.SOLUTION: Artificial expression constructs are provided that selectively regulate gene expression in selected central nervous system cell types. Such artificial expression constructs can be used to selectively express synthetic genes or alter the expression of genes in inhibitory neocortical GABAergic neurons, including somatostatin GABAergic neurons, parvalmine GABAergic neurons, vasoactive intestinal peptide GABAergic neurons, Lamp5GABA GABAergic neurons, or in some instances astrocytes.SELECTED DRAWING: Figure 2-1

The invention relates to the technical field of depression prevention and treatment, discloses an anti-depression method based on LPAG brain region GABAergic neuron regulation and control, reveals a new neural mechanism for regulating and controlling depressive disorder, develops a new theoretical understanding for the occurrence mechanism of the depressive disorder, further provides a new view angle for exploring clinical depressive disorder pathogenesis, pathogenesis and intervention measures, and provides a new application prospect. And a new intervention method is provided for clinical treatment of depressive disorder.

The application discloses application of brain-type creatine kinase in preparation of a medicine for preventing or treating Parkinson's disease, belongs to the technical field of genetic engineering, and provides the application of brain-type creatine kinase in preparation of the medicine for preventing or treating Parkinson's disease, wherein the amino acid sequence of the brain-type creatine kinase is shown as SEQ ID NO. 6. The application of brain-type creatine kinase as a treatment target in screening of the medicine for preventing or treating Parkinson's disease. The application firstly finds that in a Parkinson's disease mouse model, reducing expression of brain-type creatine kinase (CKB) increases loss and death of dopaminergic neurons in the substantia nigra pars compacta of the Parkinson's disease mouse, and significantly aggravates motor dysfunction of the Parkinson's disease mouse; overexpression of CKB obviously reduces damage of Parkinson's disease neurons. The CKB protein is a new target for preventing and treating Parkinson's disease, can be used for screening and finding the medicine for preventing and treating Parkinson's disease, can inhibit death of dopaminergic neurons by improving CKB expression, and realizes the effect of preventing and treating Parkinson's disease.

The invention discloses human-derived lactobacillus johnsonii HA1108 and application thereof in preparation of biological agents and / or medicines for treating or relieving Parkinson's disease, and belongs to the technical field of biological medicines. The invention provides a strain of lactobacillus johnsonii, which is classified and named as Lactobacillus johnsonii, and the preservation number of the lactobacillus johnsonii is CGMCC (China General Microbiological Culture Collection Center) No.35865. Based on'flora-intestine-brain axis', the lactobacillus johnsonii HA1108 can improve dyskinesia in Parkinson's disease, relieve deletion of dopaminergic neurons of nigra in the brain, increase protein expression of tyrosine hydroxylase at the nigra part in the brain, and improve the immunity of the Parkinson's disease. The microbial inoculum prepared from the lactobacillus johnsonii HA1108 does not affect the body weight after being eaten for a long time, and a new choice is provided for patients with Parkinson's disease. The screened lactobacillus johnsonii HA1108 has important significance in preparation of biological agents or medicines for treating or relieving Parkinson's disease, improving dyskinesia and improving tyrosine hydroxylase expression, has safety and application value, and is wide in market prospect.

Artificial expression constructs for modulating gene expression in targeted central nervous system cell types are described. The artificial expression constructs can be used to express synthetic genes or modify gene expression in forebrain glutamatergic neurons.

The application discloses a Pediococcus acidilactici strain and application thereof in improving neurodegeneration, improving memory and relieving anxiety. The application screens a probiotic, which is isolated and identified, and is named as Pediococcus acidilactici GXU-B2. The Pediococcus acidilactici GXU-B2 is preserved in the Guangdong Microbial Culture Collection Center (GDMCC) of the No. 59 Building, 5th Floor, Guangzhou City, at No. 100, Martyrs' Road, on November 17, 2025, and has a preservation number of GDMCC No: 67306. The Pediococcus acidilactici GXU-B2 has a neuroprotective effect, can protect dopaminergic neurons, repair intestinal barrier and reduce the concentration of plasma pro-inflammatory factors, and can improve motor dysfunction, cognitive impairment and depressive behavior. Therefore, the Pediococcus acidilactici GXU-B2 can be used for developing related products for relieving or treating neurodegenerative diseases.

The invention relates to a construction method and application of a Parkinson's disease animal model, and belongs to the technical field of animal model construction. The construction method comprises the following steps: (1) acquiring an NR4A2 flox / + mouse and a DAT cre-ERT2 mouse; (2) hybridizing the NR4A2 flox / + mouse with a DAT cre-ERT2 mouse for two times, and screening to obtain homozygous generation mice NR4A2 flox / flox and DAT cre-ERT2, wherein the NR4A2 flox / flox and the DAT cre-ERT2 are selected from the NR4A2 flox / flox and the DAT cre-ERT2; and (3) inducing the homozygous generation mice NR4A2 flox / flox and DAT cre-ERT2 by adopting the estrogen analogues, so as to obtain the Parkinson's disease model mice NR4A2 flox / flox and DAT-iCRE. The Parkinson's disease animal model which stably induces dysfunction of dopaminergic neurons of the midbrain and does not influence the survival rate of mice is successfully constructed for the first time through mouse hybridization and drug induction, and the defects that the drug stability is poor and the long disease development of PD cannot be simulated when neurotoxic drugs are injected into the abdominal cavity are effectively overcome; and the problems of poor activity, slow growth speed and low birth rate of the NR4A2 gene deletion mouse model constructed by a conventional construction method, and the limitations of difficulty in normal breeding and the like are solved.

Methods for electrical modulation of inflammation or serum TNF levels in a subject.