Application of Nrsn1 in the preparation of drugs for differentiation of neural stem cells into neuronal cells

Abstract

The present invention discloses the use of Nrsn1 in preparing a drug for differentiating neural stem cells into neurons, belonging to the field of neurobiology. The present invention proposes the use of Nrsn1 in preparing a drug for differentiating neural stem cells into neurons. The present invention also discloses the use of Nrsn1 in preparing a drug for preventing and / or treating ischemic stroke or neurodegenerative diseases. The present invention discovered that the Nrsn1 gene can promote the differentiation of neural stem cells into neurons, thereby increasing the efficiency of neural stem cell differentiation into neurons.

Description

Technical Field

[0001] The present invention relates to the field of neurobiological technology, and in particular to an application of Nrsn1 in preparing a drug for differentiating neural stem cells into neuronal cells. Background Art

[0002] Stroke, commonly known as "stroke," is a brain nerve injury disease with the highest mortality and disability rates worldwide. The pathogenesis of ischemic stroke is complex, involving damage to multiple cells in different brain regions, such as the cortex and striatum, with neuronal damage and apoptosis being particularly severe. Current clinical treatments for ischemic stroke suffer from limitations such as a short golden period, high costs, difficulty repairing the blood-brain barrier, and inability to reconstruct neural circuits. Therefore, the search for new treatments or molecular targets is urgent.

[0003] Neural stem cells have the potential to reshape damaged neural circuits and have broad application prospects. Studies have shown that exogenous NSCs transplanted into the mouse brain can promote neural recovery in mice with ischemic stroke by differentiating into neurons, thereby alleviating neural damage. However, due to the low survival rate of exogenous NSCs in the host body and the rate of their differentiation into neurons is less than 5%, the clinical trials of NSCs for the treatment of ischemic stroke are still less than ideal. Therefore, improving the survival rate of NSCs and the efficiency of their differentiation into neurons is very critical for neural repair and functional reconstruction after stroke.

[0004] How to promote the differentiation of neural stem cells into neuronal cells is a technical problem that needs to be solved by existing technologies. Summary of the Invention

[0005] Nrsn1 is a vesicle membrane protein. During chick embryonic development, Nrsn1 knockout leads to developmental impairments in Purkinje cells (efferent neurons). Furthermore, Nrsn1 is expressed at low levels in motor neurons of adult mice. While Nrsn1 may be a gene involved in neuronal development and injury repair, the relationship between Nrsn1 and the differentiation of neural stem cells (NSCs) remains unknown.

[0006] Based on this, the purpose of the present invention is to overcome the above technical deficiencies, provide an application of Nrsn1 in the preparation of drugs for differentiating neural stem cells into neuronal cells, and solve the technical problem of how to promote the differentiation of neural stem cells into neuronal cells in the prior art.

[0007] In order to achieve the above technical objectives, the technical solution of the present invention provides an application of Nrsn1 in preparing a drug for differentiating neural stem cells into neuronal cells.

[0008] In any embodiment, Nrsn1 is used in the preparation of a drug for preventing and / or treating ischemic stroke or neurodegenerative diseases.

[0009] In any embodiment, the Nrsn1 is an Nrsn1 gene or an Nrsn1 protein.

[0010] In any embodiment, the differentiation of neural stem cells into neuronal cells is promoted by upregulating the expression of the Nrsn1 gene.

[0011] In addition, the present invention also proposes the use of Nrsn1 activators or Nrsn1 mRNA in preparing drugs for preventing and / or treating neural stem cells from differentiating into neuronal cells, or in preparing drugs for preventing and / or treating ischemic stroke or neurodegenerative diseases.

[0012] In any embodiment, the Nrsn1 activator is an Nrsn1 gene activator or an Nrsn1 protein activator.

[0013] The present invention also proposes the use of Nrsn1 as a target in screening and preparing drugs for differentiating neural stem cells into neuronal cells.

[0014] The present invention also proposes the use of Nrsn1 as a target in screening and preparing drugs for preventing and / or treating ischemic stroke or neurodegenerative diseases.

[0015] The present invention also provides a drug for preventing and / or treating ischemic stroke or neurodegenerative diseases, comprising one or both of an Nrsn1 activator and Nrsn1 mRNA, and a pharmaceutically acceptable carrier.

[0016] Compared with the prior art, the present invention has the following beneficial effects: the present invention has found through a series of experiments that the Nrsn1 gene can promote the differentiation of neural stem cells into neurons and improve the efficiency of neural stem cell differentiation into neurons. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 This is a graph showing the effect of OGD / R on Nrsn1 expression in NE-4C cells according to Example 1 of the present invention;

[0018] Figure 2 This is a diagram showing the results of Nrsn1 regulating the differentiation of C17.2 cells into neuronal cells in Example 2 of the present invention;

[0019] Figure 3 This is a graph showing the effect of Nrsn1 overexpression on the differentiation of NE-4C cells treated with OGD / R in Example 3 of the present invention;

[0020] Figure 4 This is a graph showing the effect of Nrsn1 overexpression on the differentiation of C17.2 cells treated with OGD / R in Example 4 of the present invention;

[0021] Figure 5 This is a graph showing the effect of Nrsn1 knockdown on the differentiation of NE-4C cells treated with OGD / R in Example 5 of the present invention;

[0022] Figure 6 This is a graph showing the effect of Nrsn1 overexpression on NSCs differentiation in the brain of MCAO / R mice in Example 6 of the present invention;

[0023] Figure 7 This is a graph showing the effect of Nrsn1 overexpression in the brain of MCAO / R mice on the motor ability of mice in Example 7 of the present invention;

[0024] Figure 8 This is a graph showing the effect of Nrsn1 overexpression in the brain of MCAO / R mice on cerebral infarction in mice according to Example 8 of the present invention;

[0025] Figure 9 This is a graph showing the effect of Nrsn1 overexpression on neuronal and astrocyte differentiation in the brain of MCAO / R mice in Example 9 of the present invention. DETAILED DESCRIPTION

[0026] The "range" disclosed in this application is defined in the form of a lower limit and an upper limit. A given range is defined by selecting a lower limit and an upper limit, and the selected lower limit and upper limit define the boundaries of a particular range. The range defined in this way can be inclusive or exclusive of the end values, and can be arbitrarily combined, i.e., any lower limit can be combined with any upper limit to form a range. For example, if a range of 60 to 120 and 80 to 110 is listed for a particular parameter, it is understood that a range of 60 to 110 and 80 to 120 is also expected. In addition, if the minimum range values ​​listed are 1 and 2, and if the maximum range values ​​listed are 3, 4, and 5, then the following ranges can all be expected: 1 to 3, 1 to 4, 1 to 5, 2 to 3, 2 to 4, and 2 to 5. In this application, unless otherwise specified, the numerical range "a to b" represents an abbreviation of any real number combination between a and b, wherein a and b are both real numbers. For example, a numerical range of "0-5" indicates that all real numbers between "0-5" are listed herein, and "0-5" is simply an abbreviation for these numerical combinations. Furthermore, stating that a parameter is an integer ≥ 2 is equivalent to disclosing that the parameter is, for example, an integer of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, etc.

[0027] Unless otherwise specified, the terms "include" and "comprising" used in this application may be open-ended or closed-ended. For example, "include" and "comprising" may mean that other components not listed may also be included or that only the listed components are included.

[0028] Unless otherwise specified, the term "or" is used in this application to be inclusive. For example, the phrase "A or B" means "A, B, or both A and B." More specifically, the condition "A or B" is satisfied if any of the following conditions are met: A is true (or exists) and B is false (or does not exist); A is false (or does not exist) and B is true (or exists); or both A and B are true (or exist).

[0029] The present invention proposes the recovery effect of overexpressing Nrsn1 in neural stem cells on ischemic stroke. The present invention found that the Nrsn1 gene can promote the differentiation of neural stem cells into neurons, thereby promoting neural repair in mice with ischemic stroke.

[0030] We established various NSC cell lines with Nrsn1 knockdown and overexpression, and conducted in vitro experiments to verify the regulatory effects of Nrsn1 on the differentiation of various NSCs. Through molecular and cell biological approaches, we revealed the specific mechanisms by which Nrsn1 regulates the differentiation of NSCs into neurons. Overexpressing Nrsn1 in NSCs in the brains of mice with ischemic stroke revealed that Nrsn1-overexpressing NSCs repaired damaged neural circuits. This provides new targets and theoretical foundations for basic research and clinical treatment of ischemic stroke, and offers new research ideas for neural reconstruction after ischemic stroke.

[0031] This specific embodiment provides an application of Nrsn1 in preparing a drug for differentiating neural stem cells into neuronal cells.

[0032] This specific embodiment also proposes the use of Nrsn1 in the preparation of drugs for preventing and / or treating ischemic stroke or neurodegenerative diseases.

[0033] In some embodiments, the Nrsn1 is an Nrsn1 gene or an Nrsn1 protein.

[0034] In some embodiments, the differentiation of neural stem cells into neuronal cells is promoted by upregulating the expression of the Nrsn1 gene.

[0035] This specific embodiment also proposes the use of an Nrsn1 activator or Nrsn1 mRNA in preparing a drug for differentiating neural stem cells into neuronal cells, or in preparing a drug for preventing and / or treating ischemic stroke or neurodegenerative diseases.

[0036] In some embodiments, the Nrsn1 activator is an Nrsn1 gene activator or an Nrsn1 protein activator.

[0037] This specific embodiment also proposes the use of Nrsn1 as a target in screening and preparing drugs for differentiating neural stem cells into neuronal cells.

[0038] This specific embodiment also proposes the use of Nrsn1 as a target in screening and preparing drugs for preventing and / or treating ischemic stroke or neurodegenerative diseases.

[0039] This specific embodiment also provides a drug for preventing and / or treating ischemic stroke or neurodegenerative diseases, comprising one or both of an Nrsn1 activator and Nrsn1 mRNA, and a pharmaceutically acceptable carrier.

[0040] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0041] In the present invention, references to “some embodiments”, “this embodiment”, examples, etc. describe a subset of all possible embodiments, but it can be understood that “some embodiments” may be the same subset or different subsets of all possible embodiments, and may be combined with each other without conflict.

[0042] If similar descriptions of "first / second" appear in the application documents, the following explanation is added. In the following description, the terms "first\second\third" are merely used to distinguish similar objects and do not represent a specific order of the objects. It can be understood that "first\second\third" can be interchanged with the specific order or sequence where permitted, so that the embodiments described herein can be implemented in an order other than that illustrated or described herein.

[0043] In this embodiment, the term "and / or" is merely a description of the association relationship between associated objects, indicating that three relationships may exist. For example, object A and / or object B may represent three situations: object A exists alone, object A and object B exist at the same time, and object B exists alone.

[0044] Below, the embodiment of the present application is described. The embodiment described below is exemplary and is only used to explain the present application, and is not to be construed as limiting the present application. Where specific techniques or conditions are not specified in the embodiments, the techniques or conditions described in the literature in this area or the product specifications are used. Reagents or instruments used that do not specify the manufacturer are conventional products that can be obtained commercially.

[0045]

[0046] Example 1: Changes in Nrsn1 in the Neural Stem Cell Line NE-4C after OGD / R Treatment

[0047] This study involved quantitative real-time polymerase chain reaction (qRT-PCR) to examine the effects of oxygen and glucose deprivation / reperfusion (OGD / R) on Nrsn1 expression in the mouse neural stem cell line NE-4C. The experimental methods are as follows:

[0048] NE-4C cells were selected and the original culture medium was replaced with preheated Dulbecco's modified medium. The cell culture plate was placed in a hypoxic chamber with a culture environment of 5% CO2 + 94% N2 + 1% O2 and subjected to hypoxia treatment at 37°C for 2 h. Then, the Dulbecco's modified medium was immediately replaced with normal culture medium, and the cell culture plate was placed back in a cell culture incubator at 37°C and 5% CO2 under normal oxygen concentration for reoxygenation. The expression of Nrsn1 was detected by qRT-PCR at 0 h, 6 h, 12 h, 24 h, and 48 h after reoxygenation. Figure 1 * indicates P <0.05, *** indicates P <0.001. The results are as follows Figure 1 As shown, the expression level of Nrsn1 in NE-4C cells gradually increased after OGD / R treatment.

[0049] Example 2: Changes in Nrsn1 in the neural stem cell line C17.2 after OGD / R treatment

[0050] The qRT-PCR assay was used to further detect changes in Nrsn1 expression during differentiation of a second mouse neural stem cell line, C17.2. The experimental method was as follows:

[0051] C17.2 cells were selected and treated with OGD / R. The hypoxia time was set at 2h, 4h and 6h. The expression of Nrsn1, neuronal marker Tubb3b and classical genes regulating neural stem cell differentiation (Nes, Sox2, Pax6, Neurog2 and Neurod1) were detected by qRT-PCR. Figure 2 As shown in the figure, * indicates P <0.05, ** indicates P <0.01, *** indicates P<0.001, ns indicates no significant difference. The results showed that after OGD / R treatment, C17.2 cells differentiated into neurons and the expression of Nrsn1 increased.

[0052] Example 3: Effect of Nrsn1 overexpression on NE-4C cell differentiation

[0053] Lentiviral transfection was used to construct Nrsn1-overexpressing NE-4C cells. qRT-PCR, immunofluorescence, and Western blot were used to detect the differentiation of NE-4C cells after OGD / R treatment. The experimental methods are as follows:

[0054] NE-4C cells were transfected with Nrsn1 overexpression plasmid, and the transfection efficiency was detected by qRT-PCR and Western blot. Subsequently, OGD / R treatment was performed, and the expression of Tuj1 was detected by qRT-PCR, Western blot, and immunofluorescence assay. Figure 3 As shown in the figure, * indicates P <0.05, ** indicates P <0.01, ns indicates no significant difference. The results showed that Nrsn1-overexpressing NE-4C cells showed increased neuronal differentiation after OGD / R treatment.

[0055] Example 4: Effect of Nrsn1 overexpression on C17.2 cell differentiation

[0056] Lentiviral transfection was used to construct Nrsn1-overexpressing C17.2 cells. qRT-PCR, immunofluorescence, and Western blot were used to detect the differentiation of C17.2 cells after OGD / R treatment. The experimental methods are as follows:

[0057] The Nrsn1 overexpression plasmid was transfected into C17.2 cells, and the transfection efficiency was detected by qRT-PCR and Western blot. Subsequently, OGD / R treatment was performed, and the expression of Tuj1 was detected by qRT-PCR, Western blot, and immunofluorescence. Figure 4 As shown in the figure, * indicates P <0.05, ** indicates P <0.01, *** indicates P <0.001. The results showed that Nrsn1-overexpressing C17.2 cells showed increased neuronal differentiation after OGD / R treatment.

[0058] Example 5: Effect of Nrsn1 knockdown on NE-4C cell differentiation

[0059] Nrsn1 conditional knockout cells (denoted as Sh-Nrsn1) were constructed based on NE-4C cells. After OGD treatment, qRT-PCR, immunofluorescence, and Western blot experiments were used to detect whether the number of NE-4C cells differentiating into neurons was reduced. Figure 5 As shown in the figure, **** indicates P <0.0001. The results showed that Nrsn1 knockdown NE-4C cells had reduced neuronal differentiation after OGD / R treatment.

[0060] Example 6: Effect of Nrsn1 on NSCs differentiation after ischemic stroke

[0061] The MCAO / R model was constructed to simulate ischemic stroke. Adeno-associated virus (AAV) was used to overexpress Nrsn1 in the brain of MCAO / R mice. Immunofluorescence was used to detect the expression of Tuj1 and EdU in the striatum. + and EdU + The percentage of double-positive cells was compared to that of mice not injected with AAV. The experimental method is as follows:

[0062] Healthy 5-week-old C57BL / 6 male mice were selected for Nrsn1 overexpression in the brains of MCAO / R mice using intracerebroventricular injection of adeno-associated virus (AAV) at a dose of 2E+13 per mouse. Three weeks after AAV injection, mice were anesthetized with 2% isoflurane for induction and maintained with 1.5% isoflurane. The mice were secured in the supine position on the operating table. The neck hair was removed with depilatory cream to prevent bacterial infection. An incision was made in the mid-left part of the neck, and muscles and glands were separated. The pulsating common carotid artery was identified, the vagus nerve was isolated, and the common carotid vessels were clamped with an artery clamp. The external and internal carotid arteries were dissected upward along the distal end of the common carotid artery. The external carotid artery was ligated with a 5-0 suture. A small incision was made below the ligated external carotid artery with scissors. A suture was inserted up to the hemostatic clamp, then turned to insert into the internal carotid artery. The suture was advanced until it reached approximately 8-9 mm into the middle cerebral artery, stopping when slight resistance was encountered. The wound was sutured and the mouse was placed in an incubator set to 28°C. One hour after ischemia, the suture plug was removed, reperfusion was performed, and the opening was ligated with sutures, followed by closure of the wound. After the mouse regained consciousness, it was returned to its home environment, thus establishing the MCAO / R mouse model.

[0063] EdU solution was injected intraperitoneally every day at 0 h of perfusion. Brain tissue was taken for frozen section 7 days after injection. Immunofluorescence was used to detect the expression of Tuj1 and EdU in the striatum of mice. + and EdU + Whether the proportion of double-positive cells is increased compared with that of mice not injected with AAV. Figure 6As shown, the results showed that in ischemic stroke mice, the proportion of NSCs differentiated into neurons increased in Nrsn1-overexpressing mice.

[0064] Example 7: Effect of Nrsn1 overexpression on motor ability of MCAO / R mice

[0065] The study involved testing the motor abilities of MCAO / R mice using three behavioral tests, continuing until week 4. These tests included a balance beam test, a horizontal ladder test, and a rotarod test. By comparing behavioral scores, the researchers evaluated the efficacy of Nrsn1-overexpressing NSCs in improving motor and balance dysfunction in MCAO / R mice. The experimental methods were as follows:

[0066] Balance beam test: The test mice are placed on a 1 m long, 4 cm wide square wooden rod to analyze their spontaneous movements. Test durations range from 1 to 5 minutes, depending on the animal's activity level. During the test, two experimenters stand on either side of the balance beam to record the animals' upper limb movements while they face away from the experimenters. All scoring is performed blindly by the experimenters. Mice are placed in a dark room for 2 hours before the test. Three days before the test, the experimenters conduct grasping training to familiarize the animals with the experimenters' grasping method. No fasting or food rewards are required during the experiment. During the test, the number of limb slips is recorded: mice are placed on one side of a 1 m long, 4 cm wide square wooden rod and spontaneously walk to the other side. The number of limb drops is recorded. A score of 10 is assigned if the mouse does not drop at all, and one point is deducted for each slip. The test ends when the mouse crosses the balance beam into the dark room. The test score is the maximum score (10) minus the number of slips. If the mouse fails to pass or falls during the test, the lowest score (0) is recorded. The experiment is repeated three times, and the average of the three tests is calculated. After the test is completed, the animal's motor performance is evaluated by counting the number of falls on the right side (the injured side).

[0067] The rotarod test assesses the overall motor coordination of mice. During the test, mice are placed on a rotating rotarod at 30 r / min, and a timer is started. When the mouse falls from the rotarod into its corresponding channel, the latency to fall and the rotarod speed at the time of fall are recorded. A partition between channels prevents interference between mice in adjacent channels. If a mouse persists for 5 minutes without falling, the latency is recorded as 300 seconds. The test is repeated three times, with a 30-minute interval between each. To ensure test stability, two to three acclimatization training sessions are performed before each test. During the test, the time it takes for the mouse to fall from the rotarod is recorded. The mouse is placed on a rotating rotarod at 40 r / min, and a timer is started. When the mouse falls from the rotarod into its corresponding channel, the latency to fall and the rotarod speed at the time of fall are recorded. If a mouse persists for 5 minutes without falling, the latency is recorded as 300 seconds. The experiment was performed three times in succession, with an interval of 30 min between each trials.

[0068] Horizontal Ladder Test: Test mice were placed on a horizontal ladder with 70 × 15 cm side panels, spaced 5 cm apart, and instructed to walk spontaneously. The ladder's side panels contained 121 2 mm diameter circular holes spaced 5 mm apart. Stainless steel crossbars, 8 cm long and 1 mm in diameter, were inserted into the holes at irregular intervals to analyze the animals' spontaneous movements. Test durations ranged from 3 to 10 minutes, depending on the animal's activity level. During the test, two experimenters stood on either side of the ladder to simultaneously record and analyze the movements of the animal's limbs. The time required for the mouse to traverse the ladder from the starting point to the target point was recorded, excluding pauses. If the mouse failed to walk within 300 seconds, the test was terminated and the recording time was 300 seconds. After training, mice that could traverse the entire ladder within 180 seconds were selected for subsequent experiments. All scoring was performed blindly by the experimenter. Mice were kept in a dark room for 2 hours before the experiment. The test records the number of times an animal's limbs slip while walking on a horizontal ladder. A mouse is placed on one side of the ladder and spontaneously walks to the other side. The number of times the mouse's limbs fall is recorded. A score of 10 is assigned if the mouse does not fall at all, and one point is deducted for each slip. The test ends when the mouse passes the ladder. The test score is the full score (10) minus the number of slips. If the mouse fails to pass, the minimum score (0) is recorded.

[0069] like Figure 7 As shown, ** in the figure indicates P <0.01, *** indicates P <0.001. The results showed that Nrsn1 overexpression in NSCs cells promoted the recovery and improvement of motor ability in MCAO / R mice.

[0070] Example 8: Effect of Nrsn1 overexpression on cerebral infarction in MCAO / R mice

[0071] The MRI experiment detected the infarct volume in MCAO / R mice and found that Nrsn1 overexpression reduced the infarct volume in MCAO / R mice. The experimental method was as follows:

[0072] MRI examination was performed on the mouse brain to obtain high-resolution whole-brain structural images and whole-brain functional images at rest; the substantia nigra and striatum were used as seed points to analyze the differences in resting-state brain functional connectivity and changes in brain structure between the control group-MCAO / R group and the overexpression group-MCAO / R group. MRI examination was performed on the 4th week of MCAO / R modeling. During the experiment, the mice were anesthetized and brain imaging data were collected using a 2T high-magnetic field magnetic resonance imaging. The collected images include: positioning images, whole-brain high-resolution structural images, and resting-state whole-brain functional images. The structural images are planned to use the RARE sequence, and the resting-state data are planned to use the GE-EPI sequence. The differences in whole-brain resting-state functional connectivity and changes during treatment were analyzed. Body weight was monitored on days 1, 3, 5, and 7 of MCAO / R modeling to comprehensively judge the effect of Nrsn1 overexpression on cerebral infarction in MCAO / R mice. Figure 8 As shown in the figure, *** indicates P <0.001. The results showed that Nrsn1 overexpression reduced short-term weight loss in MCAO / R mice and reduced the volume of cerebral infarction in the chronic phase of MCAO / R mice.

[0073] Example 9: Effect of Nrsn1 overexpression on neuronal differentiation in the brain of MCAO / R mice

[0074] This study involved overexpressing Nrsn1 in the mouse brain using AAV to establish a MCAO / R mouse model. Immunofluorescence was used to detect the expression of GFP, Nestin, Tuj1, and NeuN in the striatum at 2 and 4 weeks, and the proportion of differentiated newborn neurons and mature neurons was calculated. The experimental methods are as follows:

[0075] Nrsn1 was overexpressed in NSCs cells of 5-week-old C57BL / 6 mice using AAV. MCAO / R mouse models were established 3 weeks after injection. Immunofluorescence was used to detect the expression of GFP, Nestin (neural stem cell marker), Tuj1 (immature neuron marker), NeuN (mature neuron marker), and GFAP (astrocyte marker) in the striatum at 2 and 4 weeks. The expression of Tuj1 was statistically analyzed. + and GFP + Double-positive cells, NeuN + and GFP + The proportion of double-positive cells was compared with that of control AAV-injected mice. Figure 9 As shown in the figure, *** indicates P <0.001. The results showed that Nrsn1 overexpression promoted the differentiation of neural stem cells into neurons in the brains of MCAO / R mice and promoted the neurological recovery of MCAO / R mice.

[0076] Compared with the prior art, other beneficial effects of the present invention include:

[0077] 1. The Nrsn1 gene of the present invention can promote the differentiation of neural stem cells into neurons and improve the efficiency of neural stem cell differentiation into neurons.

[0078] 2. The Nrsn1 gene provided by the present invention provides a new target and theoretical basis for basic research and clinical treatment of ischemic stroke.

[0079] 3. The present invention discloses a new medical use of the Nrsn1 gene in the treatment of ischemic stroke. The Nrsn1 gene can be used as a target gene. By upregulating the expression of the Nrsn1 gene, the differentiation of neural stem cells into neuronal cells can be promoted. Therefore, neural stem cells overexpressing Nrsn1 can be used in the treatment of various neurological diseases such as ischemic stroke and Alzheimer's disease. Based on the above functional characteristics, the Nrsn1 gene can be used as a potential target for the treatment of ischemic stroke, providing a new target and theoretical basis for the basic research and clinical treatment of ischemic stroke, and providing a new research idea for neural reconstruction after ischemic stroke injury.

[0080] The specific embodiments of the present invention described above do not limit the scope of protection of the present invention. Any other corresponding changes and modifications made based on the technical concept of the present invention should be included in the scope of protection of the claims of the present invention.

Claims

1. Application of Nrsn1 in the preparation of drugs for preventing and / or treating ischemic stroke.

2. The use according to claim 1, characterized in that The Nrsn1 is the Nrsn1 gene or the Nrsn1 protein.

3. The use according to claim 1, characterized in that By upregulating the expression of the Nrsn1 gene, the differentiation of neural stem cells into neuronal cells is promoted.

4. Use of Nrsn1 mRNA in the preparation of drugs for preventing and / or treating ischemic stroke.

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