47 results about "Cholinergic cells" patented technology

A specific clinical protocol for use toward therapy of defective, diseased and damaged cholinergic neurons in the mammalian brain, of particular usefulness for treatment of neurodegenerative conditions such as Alzheimer's disease. The protocol is practiced by delivering a definite concentration of recombinant neurotrophin into, or within close proximity of, identified defective, diseased or damaged brain cells. Using a viral vector, the concentration of neurotrophin delivered as part of a neurotrophic composition varies from 10<10 >to 10<15 >neurotrophin encoding viral particles / ml of composition fluid. Each delivery site receives from 2.5 mul to 25 mul of neurotrophic composition, delivered slowly, as in over a period of time ranging upwards of 10 minutes / delivery site. Each delivery site is at, or within 500 mum of, a targeted cell, and no more than about 10 mm from another delivery site. Stable in situ neurotrophin expression can be achieved for 12 months, or longer.

Provided are cortical interneurons and other neuronal cells and in vitro methods for producing such cortical interneurons and other neuronal cells by the directed differentiation of stem cells and neuronal progenitor cells. The present disclosure relates to novel methods of in vitro differentiation of stem cells and neural progenitor cells to produce several type neuronal cells and their precursor cells, including cortical interneurons, hypothalamic neurons and pre-optic cholinergic neurons. The present disclose describes the derivation of these cells via inhibiting SMAD and Wnt signaling pathways and activating SHH signaling pathway. The present disclosure relates to the novel discovery that the timing and duration of SHH activation can be harnessed to direct controlled differentiation of neural progenitor cells into either cortical interneurons, hypothalamic neurons or pre-optic cholinergic neurons. The present disclosure also relates to compositions of cortical interneurons, hypothalamic neurons or pre-optic cholinergic neurons, and their precursors, that are highly enriched and can be used in variety of application. These cells can be used therapeutically to treat neurodegenerative and neuropsychiatric disorders, and can be used for disease modeling and drug screening.

Methods of efficiently converting primate pluripotent stem cells to GABA neurons or cholinergic neurons, as well as applications thereof, are disclosed.

The invention discloses a novel application of fucoidan sulfate in prevention and cure of a parkinson disease. According to the experiments of an isolated PD cell model and an in vivo animal model, fucoidan sulfate has a certain neuroprotection effect on DA cholinergic neurons of the PD cell model and animal model and can prevent and cure the PD disease. The fucoidan sulfate of the invention can be natural polysaccharide extracts obtained form brown alga such as kelp, focus, bladder wrack, sea-tangle or chorda filum and also can be materials such as low molecular weight SSPSA or oligosaccharide which are obtained through the degradation of fucoidan sulfate.

A specific clinical protocol for use toward therapy of defective, diseased and damaged cholinergic neurons in the mammalian brain, of particular usefulness for treatment of neurodegenerative conditions such as Alzheimer's disease. The protocol is practiced by delivering a definite concentration of recombinant neurotrophin into, or within close proximity of, identified defective, diseased or damaged brain cells. Using a viral vector, the concentration of neurotrophin delivered as part of a neurotrophic composition varies from 1010 to 1015 neurotrophin encoding viral particles / ml of composition fluid. Each delivery site receives from 2.5 μl to 25 μl of neurotrophic composition, delivered slowly, as in over a period of time ranging upwards of 10 minutes / delivery site. Each delivery site is at, or within 500 μm of, a targeted cell, and no more than about 10 mm from another delivery site. Stable in situ neurotrophin expression can be achieved for 12 months, or longer.

A specific clinical protocol for use toward therapy of defective, diseased and damaged cholinergic neurons in the mammalian brain, of particular usefulness for treatment of neurodegenerative conditions such as Alzheimer's disease. The protocol is practiced by delivering a definite concentration of recombinant neurotrophin into, or within close proximity of, identified defective, diseased or damaged brain cells. Using a viral vector, the concentration of neurotrophin delivered as part of a neurotrophic composition varies from 1010 to 1015 neurotrophin encoding viral particles / ml of composition fluid. Each delivery site receives form 2.5 μl to 25 μl of neurotrophic composition delivered slowly, as in over a period of time ranging upward of 10 minutes / delivery site. Each delivery site is at, or within 500 μm of, a targeted cell, and no more than about 10 mm from another delivery site. Stable in situ neurotrophin expression can be achieved for 12 months, or longer.

The invention relates to novel polymorph crystal forms A and B of N-(2,3-dimethyl-5,6,7,8-tetrahydrofuro[2,3-b]quinolin-4-yl)-2-(2-oxopyrrolidin-1-yl)acetamide: The compounds and pharmaceutical compositions thereof are useful for activating a malfunctioned cholinergic neuron that is associated with memory loss disturbances.

The process of extracorporeal inducing nerve stem cell to directionally differentiate into cholinergic neuron includes the following steps: separating, culturing and identifying nerve stem cell; adding bFGF, heparin and laminin into F12-DMEM(1:1) culture medium with B27 in 1 % and EGF in 20 ng / mL; l inducing nerve stem cell to differentiate at 37 deg.c, 50 mL / L CO2 and saturated humidity for 7 days; and the immunogical identification of cholinergic neuron. The said process is simple and good in repeatability, and has differentiating rate over 30 %. The present invention provides new way of obtaining cholinergic neuron.

Differentiated cholinergic cells having motor neuron-like morphology and increased sensitivity to botulinum neurotoxin are provided herein. Methods of using such differentiated cells for detecting neurotoxin are also provided.

A specific clinical protocol for use toward therapy of defective, diseased and damaged cholinergic neurons in the mammalian brain, of particular usefulness for treatment of neurodegenerative conditions such as Alzheimer's disease. The protocol is practiced by delivering a definite concentration of recombinant neurotrophin into, or within close proximity of, identified defective, diseased or damaged brain cells. Using a viral vector, the concentration of neurotrophin delivered as part of a neurotrophic composition varies from 1010 to 1015 neurotrophin encoding viral particles / ml of composition fluid. Each delivery site receives form 2.5 μl to 25 μl of neurotrophic composition, delivered slowly, as in over a period of time ranging upwards of 10 minutes / delivery site. Each delivery site is at, or within 500 μm of, a targeted cell, and no more than about 10 mm from another delivery site. Stable in situ neurotrophin expression can be achieved for 12 months, or longer.

The present invention relates to a method for producing cholinergic neurons comprising obtaining neural progenitor cells from stem cells so as to continuously produce cholinergic neural cells with high purity and the same traits, followed by differentiating the neural progenitor cells into the cholinergic neurons, and cholinergic neurons produced therefrom. Since the method of preparing the cholinergic neurons provided in the present invention enables not only production of the cholinergic neurons with high purity, but also rapid production of the cholinergic neurons with the same traits, it can be widely used for effectively treating degenerative cranial nerve diseases such as Alzheimer's disease.

A specific clinical protocol for use toward therapy of defective, diseased and damaged cholinergic neurons in the mammalian brain, of particular usefulness for treatment of neurodegenerative conditions such as Alzheimer's disease. The protocol is practiced by delivering a definite concentration of recombinant neurotrophin into, or within close proximity of, identified defective, diseased or damaged brain cells. Using a viral vector, the concentration of neurotrophin delivered as part of a neurotrophic composition varies from 10<10 >to 10<15 >neurotrophin encoding viral particles / ml of composition fluid. Each delivery site receives from 2.5 mul to 25 mul of neurotrophic composition, delivered slowly, as in over a period of time ranging upwards of 10 minutes / delivery site. Each delivery site is at, or within 500 mum of, a targeted cell, and no more than about 10 mm from another delivery site. Stable in situ neurotrophin expression can be achieved for 12 months, or longer.

The invention relates to a genetic expression box, and a construction method and application of the genetic expression box. The genetic expression box comprises a neuron specific promoter, a target gene, a target sequence of gamma-aminobutyric acid cholinergic neuron specificity miRNA, and a terminator which are connected in sequence. The target sequence of the gamma-aminobutyric acid cholinergic neuron specificity miRNA is added to the tail end of the target gene of the genetic expression box, due to the fact that a gamma-aminobutyric acid cholinergic neuron contains specific miRNA, the miRNA leads the genetic expression box to keep silent in the gamma-aminobutyric acid cholinergic neuron, and the target gene can not be expressed. A serotonin cholinergic neuron contains no miRNA, is not affected by gene silencing, and can normally express the target gene, thereby being stronger in specificity. Meanwhile, the specific promoter of the entire neuron is adopted, and the expression efficiency is high when the target gene is promoted in the neuron. A recombinant expression vector constructed by utilizing the genetic expression box or the genetic expression box can be widely applied in the research field of neural circuits related to the serotonin cholinergic neuron.

The invention relates to a cell line of precursor of forebrain nerve of a telomerase immortalization human embryo and an establishing method and application thereof; the cell line is preserved in China culture collection and management committee general biology center in 21st February 2008, with the collection number of CGMCC No.2372. The cell line of the invention is named as hSN12W-TERT; the cell line expresses growth factor receptor of human nerves and green fluorescent protein, has high activity of telomerase, double core type than normal human, continuous passage culture in vitro of 36 months with 45th generation at the present and population doubling of 100 to 200 times and has the property of contact inhibition and density inhibition; the neuron which is formed by differentiation of the cell line has the property of electrophysiology; the cell line can be differentiated into Gamma-aminobutyric acid (GABA) cholinergic neuron under the induction of bone marphogenic protein 2(BMP2).

The invention provides for methods of upregulating endogenous GDNF by inhibiting Shh signaling. The invention further provides a method for increasing the production of cholinergic neurons and dopamine neurons by subventricular zone (SVZ) neurogenesis in a subject. The invention further provides methods for treating a neurodegenerative disorder in a subject.

The invention relates to methods and compositions for developing basal forebrain cholinergic neurons (BFCNs) from stem cells, and in particular, BFCNs having repaired electrophysiological defects relating to one or more mutations in PSEN2, and to the use of such BFCNs in cell-based therapies to treat Alzheimer's disease.

The invention discloses a method for promoting differentiation of hippocampal neural stem cells to cholinergic neurons, comprising the following steps of: separating hippocampus NSCs, inoculating, culturing with an NSCs culture solution, adding viruses, removing the NSCs culture solution after a certain period of time, and replacing with a fresh NSCs culture solution to continue culturing; whereinthe virus is a GAS5 overexpression lentivirus; and the MOI value of the added virus is 5-100. According to the invention, the expression quantity of GAS5 can be remarkably increased, and the proportion of hippocampus neural stem cells differentiating to cholinergic neurons can be remarkably increased.

The invention discloses an application of mussaenda erythrophylla glucoside U in preparation of an antiacetyl-choline medicine. An inventor researches influences of mussaenda erythrophylla glucoside U to contractility of ileum smooth muscles of in-vitro guinea pig caused by acetylcholine bromide and the influences to mouse pupil diameter, sialaden secretion quantity and small intestine carbon powder promotion percentage of an M cholinergic neuron excitation model caused by pilocarpine, and the results prove that the of mussaenda erythrophylla glucoside U is the antiacetyl-choline medicine. By performing a mouse acute toxicity test, the half lethal dose of the mussaenda erythrophylla glucoside U for intravenous injection is obtained, and a proper dose of the mussaenda erythrophylla glucoside U for antiacetyl-choline intravenous injection can be obtained by means of calculation based on a mouse in-vivo test dose. Therefore, after a proper dose of the mussaenda erythrophylla glucoside U is taken by a person by intravenous injection or by other methods, a pharmacodynamic effect the same as that of atropine can be played. Thus, the mussaenda erythrophylla glucoside U and a medicine excipient are used for preparing an antiacetyl-choline medicine preparation which can be used for treating clinical patients with organophosphorus nerve agent poisoning, acute microcirculation disturbance, stomach and intestine cramp and biliary tract or urethral canal spasmodic pain.

The invention relates to novel polymorph crystal forms A and B of N-(2,3-dimethyl-5,6,7,8-tetrahydrofuro[2,3-b]quinolin-4-yl)-2-(2-oxopyrrolidin-1-yl)acetamide: The compounds and pharmaceutical compositions thereof are useful for activating a malfunctioned cholinergic neuron that is associated with memory loss disturbances.

System and method for treating intractable epilepsy are provided. The method includes implanting electrodes in pedunculopontine nucleus and delivering electrical pulses to the pedunculopontine nucleus, thereby inducing the stimulation of cholinergic neurons leading to the release of acetylcholine, thereby enhancing the genesis of rapid eye movement sleep, which reduces the occurrence of epileptic attacks and also chronically suppresses the epileptogenic process.

A method of treating a subject and preventing in a subject age-dependent basal forebrain cholinergic dysfunction related neurodegenerative disorders, comprising: administering a lipid composition comprising a therapeutically effective amount of highly enriched 1-acyl chains / 2-docosahexaenoic acid containing molecular species of highly pure phospholipids to promote survival of aged basal forebrain cholinergic neurons, the phospholipids selected from the group consisting of phosphatidylserine, phosphatidylethanolamine, and phosphatidyl-monomethylethanolamine. A composition for treating a subject and preventing in a subject age-dependent basal forebrain cholinergic dysfunction related neurodegenerative disorders, the composition comprising: a lipid composition comprising: a therapeutically effective amount of highly enriched 1-acyl chains / 2-docosahexaenoic acid containing molecular species of highly pure phospholipids to promote survival of aged basal forebrain cholinergic neurons, the phospholipids selected from the group consisting of phosphatidylserine, phosphatidylethanolamine, and phosphatidyl-monomethylethanolamine. A process for preparing a lipid composition comprising a therapeutically amount of natural source-based highly enriched 1-acyl chains / 2-docosahexaenoic acid containing molecular species of highly pure phosphatidylserine to promote survival of aged basal forebrain cholinergic neurons; the process comprising: purifying a natural source-based phosphatidylcholine by silica chromatography; obtaining a related lysophosphatidylserine species by phospholipase A2 catalysis of transphosphatidylated natural source-based phosphatidylserine species; acylating the lysophosphatidylserine species with natural docosahexaenoic acid to form 1-acyl chains / 2-docosahexaenoic acid containing phosphatidylserine species; and purifying the 1-acyl cgains / 2-docosahexaenoic acid containing phosphatidylserine species by silica chromatography.

The invention discloses application of 3,4-methyl dihydroxybenzoate (MDHB) in preparation of drugs for inducing directional differentiation of neural stem cells or neural precursor cells. The invention discovers that MDHB has the effect of directionally inducing differentiation of neural stem cells or neural precursor cells to cholinergic neurons, can be used for developing drugs for curing related diseases (SCI, AD and the like) of cholinergic neuron damage and loss, can be used for cell transplantation therapy of related diseases (SCI, AD and the like) of cholinergic neuron damage and loss, and can be used for developing directional inducers and the like of neural stem cells or neural precursor cells. The new pharmacological activity of MDHB is determined, the illumination of a pesticide effect mechanism provides reference for developing new drugs with proprietary intellectual property rights, MDHB is applied to basic experiments in the field of neurosciences, and a novel method is provided for searching models of cholinergic neurons.

The invention discloses treatment effect of a compound medicine on alzheimer's disease. The compound medicine is composed of galanthamine and meclofenoxate in a combination and matching dosage proportion of (0.5-4):(17.5-70), preferable 2:35. Under the matching condition, galanthamine and meclofenoxate are combined to achieve obvious improving effect for memory acquisition disorder, memory consolidation disorder and memory representation disorder. Meanwhile, the compound medicine can achieve effects of preventing and treating the alzheimer's disease by delaying brain ageing, reducing amyloid deposition in brain, protecting cholinergic neuron and the like. Moreover, learning memory can be improved and the alzheimer's disease can be prevented and treated by combined use of galanthamine and meclofenoxate.

The invention relates to a method for preparing basal forebrain cholinergic neurons reserving age characteristics through non-nerve cell transformation. According to the preparation method disclosed by the invention, key cell direct transdifferentiation gene combinations and promoters for regulating and controlling the expression level are optimized, viruses capable of efficiently infecting donor-derived cells of various ages are packaged, and adherent growth of the donor-derived cells and transformed neuronal cells is promoted by adopting a proper coating matrix; an induced differentiation culture solution containing small molecular compounds capable of promoting transdifferentiation and growth factors is utilized; a large number of basal forebrain cholinergic neurons are obtained throughtransdifferentiation after the differentiation culture solution is replaced for multiple times within 10-14 days; and finally, the high-purity basal forebrain cholinergic neurons are obtained throughseparation and purification.

The invention discloses a method for constructing a female AD model by utilizing an oxytocin receptor gene silencing technology and an identification method. Constructing and screening are carried outto obtain an AAV9-Oxtr-RNAi vector, AAV9-Oxtr-RNAi viruses are injected into a rat basal nucleus region by utilizing brain stereotaxis, according to a brain infection pathological state, detection and evaluation are carried out in combination with senile dementia symptoms caused by estrogen decline of clinical women, rats are randomly divided into a sham group, a con-shRNA control group and an OXTR-shRNA group, and the learning and memory abilities of the rats are detected by adopting a behavioral Morris water maze experiment and a bright and dark box experiment; an Elisa kit is used for detecting the change of the level of the rat brain tissue cortical estrogen (Estrogen, E2) and the change of the level of a acetylcholine neurotransmitter (acetylcholine, Ach); and in combination with animmunofluorescence technology, the co-localization and expression conditions of incoming nerve fibers of hippocampus in a brain basal nuclear cholinergic neuron fiber projection region, OTR and ChAT are observed, and a basis can be provided for better exploring and researching the pathogenesis and pathological changes of female Alzheimer disease.

The invention discloses a 1, 2, 3, 4-tetrahydroacridine-9-amine compound as well as a preparation method and application thereof. The compound is characterized in that: tacrine is taken as a parent nucleus; the compound has structural formulas shown in formulas I and II or pharmaceutically acceptable salts, esters or solvates of the compounds shown in the formulas I and II; and the compound can beused for preparing medicines for resisting Alzheimer's disease, medicines for delaying neurodegenerative diseases, medicines for repairing cholinergic neurons in vitro, medicines for resisting oxidative stress injury in vitro and medicines for relieving beta-amyloid protein (A beta) neurotoxicity, improving cognitive disorder through a CREB-ERK pathway or improving cognitive disorder through reducing Tau protein phosphorylation. Thecompound has the advantage of excellent anti-Alzheimer's disease activity.

Provided is a substance which is a safe material such as a food component and an extract of a natural product and has a stronger effect of ameliorating a cerebral function (effect of ameliorating a metabolism of monoamines as an intracerebral neurotransmitter and ameliorating deterioration in memory and learning due to hypofunction of a cholinergic neuron). The present invention provides a composition for ameliorating a cerebral function, comprising an alkali-stable lipid from an acetic acid bacterium, N-acylsphinganine or N-2′-hydroxypalmitoyl-sphinganine, as an active ingredient.

Methods of efficiently converting primate pluripotent stem cells to GABA neurons or cholinergic neurons, as well as applications thereof, are disclosed.

The invention discloses a method for constructing an animal brain injury model based on hippocampal cholinergic neuron regulation, which comprises the following steps: setting electromagnetic radiation conditions, and carrying out electromagnetic radiation treatment on a test animal; and comparing the influence of cholinergic neuron activation or inhibition of the hippocampal CA3 region of the experimental animal on the behavior of the experimental animal before and after the electromagnetic radiation treatment, and if the influence on the behavior of the experimental animal has statistical significance, constructing the electromagnetic radiation animal brain injury model by utilizing the electromagnetic radiation condition. According to the method, the electromagnetic radiation animal brain injury model can be well constructed, and possibility is increased for clarification of the molecular mechanism of the electromagnetic radiation brain injury effect and research and development of prevention and treatment drugs.