Use of cytokine CXCL10 in depression and / or anxiety disorders

By using the cytokine CXCL10 to prepare the drug, leukocytes are activated to regulate the immune response, which solves the problems of low efficacy and large side effects in existing treatments for depression and anxiety disorders, and achieves rapid and safe therapeutic effects.

WO2025247345A1PCT designated stage Publication Date: 2025-12-04SHANGHAI JIAOTONG UNIV
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Patent Information

Application Number
PCT/CN2025/098136
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2024-05-30
Filing Date
2025-05-29
Publication Date
2025-12-04

AI Technical Summary

Technical Problem

Existing medications for depression and anxiety disorders have low efficacy, slow onset of action, significant side effects, and high relapse rates, and there is a lack of precise and safe treatment options.

Method used

Drugs prepared using the cytokine CXCL10 are used to prevent and treat depression and anxiety disorders by activating leukocytes to regulate immune responses and improve symptoms.

Benefits of technology

It significantly shortens immobility time in patients with depression and anxiety, reduces the level of despair, improves anhedonia, reduces anxiety, enhances resistance to defiance and "exploration-avoidance" conflict behaviors, and has high safety at low doses and can cross the blood-brain barrier to exert its effects.

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Abstract

The present invention relates to the use of cytokine CXCL10 in depression and / or anxiety disorders.
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Description

Application of cytokine CXCL10 in depression and / or anxiety disorders Technical Field

[0001] This invention relates to the field of medicine, and more specifically to the application of cytokine CXCL10 in depression and / or anxiety disorders. Background Technology

[0002] Depression and anxiety disorders are two of the most common mental disorders in modern society. They often coexist as comorbidities, affecting more than 300 million people worldwide. The pathophysiological mechanisms of these disorders are not yet fully understood, posing challenges to treatment.

[0003] In the clinical treatment of depression, commonly used first-line drugs include fluoxetine (a selective serotonin reuptake inhibitor, SSRI) and venlafaxine (a serotonin-norepinephrine reuptake inhibitor, SNRI). These drugs are also suitable for the treatment of anxiety disorders. However, the efficacy of these drugs in clinical use is approximately 30%, and they suffer from slow onset of action (generally requiring 4 to 6 weeks or longer), significant side effects, and a high relapse rate. On the other hand, second-generation antidepressants, represented by ketamine, face safety challenges such as addiction, hallucinations, and cognitive impairment. Currently, these drugs are mainly used for patients at high suicide risk or in treatment-resistant conditions, requiring strict monitoring and management during treatment. Given these challenges, the development of novel, more precise, and applicable drug treatment regimens for depression and anxiety disorders has become an urgent need in the field of psychiatry. Summary of the Invention

[0004] The purpose of this invention is to provide the use of cytokine CXCL10 in the preparation of a medicament for treating depression and / or anxiety disorders.

[0005] In a first aspect, the present invention provides the use of the cytokine CXCL10 for the preparation of a medicament for the prevention and / or treatment of depression and / or anxiety disorders.

[0006] In another preferred embodiment, the cytokine CXCL10 has the amino acid sequence shown in SEQ ID NO:1.

[0007] In another preferred embodiment, the CXCR3 blocking polypeptide has the amino acid sequence shown in SEQ ID NO:2.

[0008] In another preferred embodiment, the drug is used for one or more purposes selected from the group consisting of:

[0009] 1) Used to shorten immobility time in patients with depression and / or anxiety disorders;

[0010] 2) Used to reduce the level of despair in patients with depression and / or anxiety disorders;

[0011] 3) Used to improve anhedonia in patients with depression and / or anxiety disorders;

[0012] 4) Used to reduce anxiety levels in patients with depression and / or anxiety disorders.

[0013] In another preferred embodiment, the patient with depression and / or anxiety disorder is a person.

[0014] In another preferred embodiment, the drug is used to enhance the level of resistance behavior in patients with depression and / or anxiety disorders during difficult situations.

[0015] In another preferred embodiment, the drug is used to enhance the resistance of patients with depression and / or anxiety disorders to "exploration-avoidance" conflict behaviors, thereby increasing their probability of choosing exploratory behaviors.

[0016] In another preferred embodiment, the drug is administered after a model of depression and / or anxiety disorder.

[0017] In another preferred embodiment, the depression and / or anxiety disorder is a depression and / or anxiety disorder associated with different depression models.

[0018] In another preferred embodiment, the depression and / or anxiety disorder is modeled by a chronic restraint stress model.

[0019] In another preferred embodiment, the depression and / or anxiety disorder is modeled by a chronic unpredictable mild stress model.

[0020] In another preferred embodiment, the depression and / or anxiety disorder is modeled by a social isolation model.

[0021] In another preferred embodiment, the method of administration of the drug is selected from the group consisting of intravenous injection, subcutaneous injection, and nasal inhalation.

[0022] In another preferred embodiment, the drug is administered via tail vein injection.

[0023] In another preferred embodiment, the dosage of the drug is 0.5-2 ng per mouse.

[0024] In another preferred embodiment, the dosage of the drug is 0.8-1.5 ng per mouse (preferably 1-1.2 ng).

[0025] In another preferred embodiment, the depression and / or anxiety disorder is a depression and / or anxiety disorder with low CXCL10 expression.

[0026] In another preferred embodiment, the depression and / or anxiety disorder is a depression and / or anxiety disorder with low expression of CXCL10 in peripheral monocytes / macrophages and in the brain.

[0027] In another preferred embodiment, the depression and / or anxiety disorder is a CXCR3-related depression and / or anxiety disorder.

[0028] In another preferred embodiment, the drug is capable of crossing the blood-brain barrier.

[0029] In a second aspect, the present invention provides a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a safe and effective amount of the cytokine CXCL10.

[0030] A third aspect of the invention provides the use of the pharmaceutical composition described in the second aspect of the invention for the prevention and / or treatment of depression and / or anxiety disorders.

[0031] It should be understood that, within the scope of this invention, the above-described technical features of this invention and the technical features specifically described below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be described in detail here. Attached Figure Description

[0032] Figure 1. Low-dose CXCL10 administration via tail vein can alleviate depression and anxiety-like behaviors in CRS model mice. (a) Tail suspension test results, (b) Forced swimming test results, (c) Sucrose preference test results, (d) Elevated cross maze test results, (e) Open field test results.

[0033] Figure 2. Low-dose CXCL10 administration via tail vein can alleviate depression and anxiety-like behaviors in CUMS model mice. (a) Tail suspension test results, (b) Forced swimming test results, (c) Sucrose preference test results, (d) Elevated cross maze test results, (e) Open field test results.

[0034] Figure 3. Low-dose CXCL10 administration via tail vein can alleviate depression and anxiety-like behaviors in SI model mice. (a) Tail suspension test results, (b) Forced swimming test results, (c) Sucrose preference test results, (d) Elevated cross maze test results, (e) Open field test results.

[0035] Figure 4. Induction of depression / anxiety-like behavior in mice by tail vein injection of a blocking peptide of CXCR3. (a) Tail suspension test results, (b) Forced swimming test results, (c) Sucrose preference test results, (d) Elevated cross maze test results, (e) Open field test results.

[0036] Figure 5: Cy5.5-labeled CXCL10 injected via tail vein can cross the blood-brain barrier and enter the brain. Detailed Implementation

[0037] Through long-term and in-depth research, the inventors have made an innovative discovery that the cytokine CXCL10 has excellent effects in treating depression and / or anxiety disorders.

[0038] Specifically, administration of the cytokine CXCL10 after model establishment significantly improved the depressive and / or anxiety symptoms of research subjects. It significantly improved depressive and / or anxiety symptoms in chronic restraint stress-induced depression models, chronic unpredictable stress-induced depression models, and social isolation-induced depression models, thus demonstrating a therapeutic effect on the development of depression and / or anxiety. Based on this, the inventors completed this invention.

[0039] Cytokine CXCL10

[0040] CXCL10 is a small cytokine belonging to the CXC chemokine family. CXCL10 binds to the CXCR3 receptor and regulates immune responses by activating and recruiting leukocytes (such as T cells, eosinophils, and monocytes). Studies have found that CXCL10 has anti-tumor and angiogenesis-promoting effects. However, no studies have yet established a correlation between CXCL10 and depression or anxiety disorders.

[0041] CXCL10 has the amino acid sequence shown in SEQ ID NO:1.

[0042] Pharmaceutical Composition

[0043] The present invention also provides a pharmaceutical composition comprising a pharmaceutically acceptable carrier and one or more safe and effective amounts of the cytokine CXCL10.

[0044] The pharmaceutical composition of the present invention comprises cytokine CXCL10 within a safe and effective range and a pharmacologically acceptable excipient or carrier. "Safe and effective range" refers to an amount of cytokine CXCL10 sufficient to significantly improve the condition without causing serious side effects. Typically, the pharmaceutical composition contains 0.1-200 mg of cytokine CXCL10 per dose, more preferably 1-100 mg of cytokine CXCL10 per dose.

[0045] "Pharmaceuticalally acceptable carriers" refer to substances that are suitable for use in humans and / or animals without excessive adverse side effects (such as toxicity, irritation, and allergic reactions), i.e., substances with a reasonable benefit / risk ratio.

[0046] It should be understood that the carrier described in this invention is not particularly limited and is a commonly used material in the field, the type of which, the method of use, and the source are well known to those skilled in the art.

[0047] Pharmaceutically acceptable examples of carrier components include cellulose and its derivatives (such as methylcellulose, ethylcellulose, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, etc.), gelatin, talc, solid lubricants (such as stearic acid, magnesium stearate), calcium sulfate, vegetable oils (such as soybean oil, sesame oil, peanut oil, olive oil, etc.), polyols (such as propylene glycol, glycerin, mannitol, sorbitol, etc.), emulsifiers (such as Tween), wetting agents (such as sodium dodecyl sulfate), buffers, chelating agents, thickeners, pH adjusters, transdermal penetration enhancers, colorants, flavoring agents, stabilizers, antioxidants, preservatives, antibacterial agents, pyrogen-free water, etc.

[0048] The pharmaceutical composition is an injection or an inhalation.

[0049] There are no particular limitations on the administration method of the pharmaceutical composition of the present invention. Representative administration methods include (but are not limited to): intravenous injection, subcutaneous injection and nasal inhalation.

[0050] Compositions for parenteral injection may comprise physiologically acceptable sterile aqueous or anhydrous solutions, dispersions, suspensions, or emulsions, and sterile powders for reconstitution into sterile injectable solutions or dispersions. Suitable aqueous and non-aqueous carriers, diluents, solvents, or excipients include water, ethanol, polyols, and suitable mixtures thereof.

[0051] The cytokine CXCL10 of this invention can be administered alone or in combination with other pharmaceutically acceptable drugs (such as antidepressants and / or anxiety disorder drugs).

[0052] The treatment method of the present invention can be used alone or in combination with other treatment methods or drugs.

[0053] When using a pharmaceutical composition, a safe and effective amount of the cytokine CXCL10 is administered to the mammal (such as a human) requiring treatment. The dosage at the time of administration is the pharmaceutically considered effective dose. Of course, the specific dosage should also take into account factors such as the route of administration and the patient's health condition, which are all within the scope of a skilled physician's expertise.

[0054] Indications

[0055] This invention uses different mouse models of depression and anxiety. Adding the cytokine CXCL10 of this invention to the drug can significantly alleviate the depression and anxiety-like behaviors of the model mice. Furthermore, blocking the receptor CXCR3 of the cytokine of this invention leads to depression and anxiety-like behaviors in mice.

[0056] Compared with the prior art, the present invention has the following main advantages:

[0057] (1) The cytokines described in this invention have significant therapeutic effects on depression and / or anxiety disorders;

[0058] (2) The cytokines described in this invention are effective at low doses and have higher safety.

[0059] (3) The cytokines described in this invention can cross the blood-brain barrier to exert their effects when used to treat depression and / or anxiety disorders.

[0060] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods in the following embodiments, unless otherwise specified, are generally performed under conventional conditions as described in Sambrook et al., Molecular Cloning: A Laboratory Manual (New York: Cold Spring Harbor Laboratory Press, 1989), or as recommended by the manufacturer. Unless otherwise stated, percentages and parts are by weight.

[0061] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as are familiar to those skilled in the art. Furthermore, any methods and materials similar to or equivalent to those described herein may be applied to the methods of this invention. The preferred embodiments and materials described herein are for illustrative purposes only.

[0062] general material

[0063] CXCL10: Purchased from MedChemExpress Biotechnology Company, USA, catalog number HY-P7227.

[0064] CXCR3 blocking peptide: purchased from Beijing Bio-Sens Biotechnology Co., Ltd., catalog number bs-1502P.

[0065] Example 1: The efficacy and mechanism of action of CXCL10 in the treatment of depression and anxiety.

[0066] 1. Laboratory animals:

[0067] SPF-grade newborn C57BL / 6 mice, 6-12 weeks old, male, weighing approximately 20-28g, were purchased from Shanghai Silex Laboratory Animal Co., Ltd. The mice were housed and managed by the Laboratory Animal Center of Shanghai Jiao Tong University, and were SPF-grade (specific pathogen-free). Stable housing conditions were maintained, including constant temperature and humidity, 12-hour light and 12-hour darkness, with free access to water and food. No more than 5 mice were housed per cage.

[0068] 2. Modeling methods

[0069] 2.1 Chronic restraint stress (CRS) model:

[0070] Mice were restrained for 6 hours daily for 21 days using a mouse restraint device. After establishing the model, behavioral experiments such as the tail suspension test, forced swimming test, sucrose preference test, elevated cross maze test, and open field test were used to assess the mice's despair, anhedonia, anxiety, and motor abilities.

[0071] 2.2 Chronic unpredictable mild stress (CUMS) model:

[0072] Mice were exposed to mild social and environmental stressors 2-3 times daily for 10 weeks. Stressors included: 1) 24-hour food deprivation; 2) 24-hour water deprivation; 3) nighttime lighting (mice were placed in a bright environment from 7:00 PM to 7:00 AM the following day); 4) removal of bedding for 24 hours; 5) dirty cage (200 ml water in 100 g bedding) for 24 hours; 6) forced swimming in 4°C water for 6 minutes; 7) tail clamping (1 cm from the tail tip) for 5 minutes; 8) restraint for 2 hours; 9) forced swimming in 45°C water for 6 minutes; and 10) normal feeding for 24 hours. Different stressors were applied randomly for each day. After establishing the model, behavioral tests such as the tail suspension test, forced swimming test, sucrose preference test, elevated cross maze test, and open field test were used to assess the mice's despair, anhedonia, anxiety, and motor skills.

[0073] 2.3 Social Isolation (SI) Model:

[0074] Five mice were housed in a cage in the control group, while mice in the model group were housed individually in cages for 21 days. After establishing the model, behavioral experiments such as the tail suspension test, forced swimming test, sucrose preference test, elevated cross maze test, and open field test were used to detect the mice's despair, anhedonia, anxiety, and motor ability.

[0075] 3. Handling method:

[0076] 3.1 The role of CXCL10 in a chronic restraint stress-induced depression model: related experimental treatment methods

[0077] 3.1.1 Intervention via tail vein administration of medication

[0078] Control group: Mice were injected with solvent via tail vein on days 15, 18 and 21 after one week of acclimatization.

[0079] Model group: After mice adapted to the environment for one week, their movement was restricted by a mouse restraint device for 6 hours daily for 21 days. Solvent was injected via tail vein on days 15, 18, and 21.

[0080] Model group + CXCL10 intervention group: After mice adapted to the environment for one week, their movement was restricted for 6 hours daily using a mouse restraint device for 21 days. CXCL10 was administered via tail vein on days 15, 18, and 21. The dosage was 1 ng per mouse.

[0081] 3.2 The role of CXCL10 in a chronic, unpredictable, mild stress-induced depression model: related experimental treatment methods

[0082] 3.2.1 Intervention via tail vein administration of medication

[0083] Control group: Mice were injected with solvent starting in week 10 after one week of acclimatization, once every three days via tail vein injection, for a total of three injections.

[0084] Model group: Mice were exposed to two social and environmental stressors daily for 10 weeks after acclimatizing to the environment for one week. Solvents were injected starting in week 10, once every three days via tail vein, for a total of three injections.

[0085] Model group + CXCL10 intervention group: After mice adapted to the environment for one week, they were exposed to two social and environmental stressors daily for 10 weeks. Starting in week 10, CXCL10 was administered at a dose of 1 ng per mouse, injected via the tail vein every three days for three weeks.

[0086] 3.3 The role of CXCL10 in a social isolation depression model: related experimental treatment methods

[0087] 3.3.1 Intervention via tail vein administration of medication

[0088] Control group: Mice (5 mice per cage) were acclimatized to the environment for one week, and then injected with solvent via tail vein on the fifteenth, eighteenth and twenty-first day.

[0089] Model group: Mice (5 mice per cage) were housed individually in cages for 21 days after acclimatizing to the environment for one week. Solvent was injected via tail vein on days 15, 18, and 21.

[0090] Model group + CXCL10 intervention group: After mice (5 mice per cage) acclimatized to the environment for one week, they were housed individually for 21 days. The drugs were administered via tail vein on days 15, 18, and 21. The dosage was 1 ng per mouse.

[0091] 3.4 Experimental Treatment Methods for Influence of CXCR3 Blocking Peptide on Depression- and Anxiety-like Behaviors in Mice

[0092] 3.4.1 Intervention via tail vein administration of medication

[0093] Control group: Mice were injected with solvent via tail vein on days 15, 18 and 21 after one week of acclimatization.

[0094] Model group: After mice adapted to the environment for one week, their movement was restricted by a mouse restraint device for 6 hours daily for 21 days. Solvent was injected via tail vein on days 15, 18, and 21.

[0095] CXCR3 blocking peptide intervention group: After mice acclimatized to the environment for one week, they were fed normally for 21 days. CXCR3 blocking peptide was administered via tail vein on days 15, 18, and 21. The dosage was 60 μg per mouse.

[0096] 3.5 Experimental procedures for CXCL10 blood-brain barrier permeability testing

[0097] 3.5.1 Control group: Mice were injected with solvent via the tail vein.

[0098] CXCL10 administration group: C57BL / 6J wild-type mice were administered CXCL10 labeled with Cy5.5 via the tail vein at a dose of 0.2 mg / kg. The distribution of CXCL10-Cy5.5 in the mice was detected by a small animal three-dimensional imaging system at 4 h and 8 h. The mice were dehaired before imaging.

[0099] 4. Mouse behavioral experiments

[0100] 4.1 Tail Suspension Test (TST)

[0101] Under acoustic and visual isolation, the animal was suspended at least 80 cm above the floor using tape placed approximately 1 cm from the tip of its tail. The total TST procedure was 6 minutes, with the immobility time recorded during the last 4 minutes; the mouse was considered immobile only when passively suspended and stationary.

[0102] 4.2 Forced swimming test (FST)

[0103] Each mouse was placed individually in a 4000 mL glass beaker containing 3000 mL of warm water (temperature 25±1℃). The entire FST procedure lasted 6 minutes, and the immobility time during the last 4 minutes was recorded; a mouse was considered immobile only if it remained still, floated, or made only minor movements necessary to keep its head above the water surface.

[0104] 4.3 Sucrose Preference Test (SPT)

[0105] The experiment used a 2% fresh sucrose solution and normal drinking water for mice. Mice were acclimatized to the 2% fresh sucrose solution for 12 hours, then deprived of water and food for another 12 hours. Mice were divided into individual cages, and each cage was given one bottle of 2% fresh sucrose solution and normal water. After 12 hours, the consumption of the 2% fresh sucrose solution and drinking water was measured and calculated. Based on these values, the mice's sucrose preference level was calculated. Sucrose preference = 2% fresh sucrose solution consumption / (2% fresh sucrose solution consumption + drinking water consumption).

[0106] 4.4 Elevated Plus-Maze Test (EPM)

[0107] One week prior to the experiment, the animals were petted for 1-5 minutes daily for 7 consecutive days to reduce their fear of the experimenter. The animals were placed in the central area of ​​the maze, heads facing the open arms, and each animal was placed in the same position thereafter. A video monitor was simultaneously activated to record the number of times each animal entered the maze (open and closed arms) within 5 minutes, as well as the time taken to enter each arm. The experimenter remained 1 meter away from the maze during the experiment. After recording, the animals were returned to their cages. The maze was then cleaned and wiped with 75% alcohol to eliminate the influence of animal odors on subsequent animals. Percentage of animals entering through open arms = Number of animals entering through open arms / (Number of animals entering through open arms + Number of animals entering through closed arms)

[0108] 4.5 Open field test (OFT)

[0109] Mice were placed in the central area of ​​the experimental chamber, and a monitor was activated to record the total distance the mice traveled within the chamber over 5 minutes. After the experiment, the mice were returned to their cages, and the maze was cleaned with 75% alcohol to eliminate the influence of animal odors on subsequent mice.

[0110] 5. Experimental Evaluation Indicators

[0111] 5.1 Behavioral Indicators of Mice

[0112] 5.1.1 The forced swimming test and the tail suspension test are the most commonly used experimental methods for detecting depressive-like behavior in rodents, mainly used to assess the degree of behavioral despair in mice. Normal mice, when placed in an inescapable environment (water tank or hanging position), will exhibit active swimming or struggling behavior for a prolonged period. If a mouse is in a depressive state, after the initial swimming or struggling, it will exhibit a prolonged state of immobility and despair. We reflect the degree of despair in mice by recording the time they remain immobile within a certain period.

[0113] 5.1.2 Because rodents have an innate and strong craving for sweets, normal mice experience pleasure from drinking 2% sucrose, prompting them to selectively drink excessive amounts of sucrose solution rather than plain water. In depressed model mice, drinking sugar water does not induce pleasure, therefore they do not selectively drink excessive amounts of sugar water. Based on this, calculating the sucrose preference level in mice can help analyze the degree of anhedonia.

[0114] 5.1.3 The elevated cross maze utilizes the contradictory behavior of animals' exploratory nature towards novel environments and their fear of open, suspended arms to examine their anxiety levels. The elevated cross maze has one pair of open arms and one pair of closed arms. Rodents, due to their dark-loving nature, tend to move in the closed arms, but out of curiosity and exploration, they also move in the open arms. When faced with novel stimuli, animals simultaneously experience the impulse to explore and fear, creating a conflict between exploration and avoidance, thus generating anxiety. We used the frequency with which mice entered the open arms to reflect their anxiety levels; the higher the anxiety level, the lower the frequency of entering the open arms.

[0115] 5.1.4 The total distance traveled by mice in the open field experiment reflects the mice's motor ability.

[0116] 6. Experimental Results:

[0117] 6.1 Low-dose CXCL10 significantly improved depression and anxiety-like behaviors in a mouse model of depression.

[0118] CRS, CUMS, and SI models of mice all exhibited depression and anxiety-like behaviors, specifically, in the FST and TST experiments, the immobility time of mice after modeling was significantly higher than that of the control group (Fig. 1a, b; Fig. 2a, b; Fig. 3a, b). In the SPT experiment, the sucrose preference of mice in the model group was significantly reduced (Fig. 1c; Fig. 2c; Fig. 3c). In the EPM experiment, the frequency of mice entering open arms was significantly reduced after modeling (Fig. 1d; Fig. 2d; Fig. 3d). The total distance in the OFT experiment did not differ among the groups, excluding the influence of the mice's voluntary movement ability on the behavioral experiments (Fig. 1e; Fig. 2e; Fig. 3e). Therefore, low-dose administration of CXCL10 is therapeutically effective for depression / anxiety behaviors induced by chronic restraint stress, chronic unpredictable mild stress, and social separation.

[0119] 6.2 Blocking the CXCL10 functional receptor CXCR3 induces depression / anxiety-like behavior in mice.

[0120] In the FST and TST experiments, similar to the CRS group, the immobility time of mice in the CXCR3-blocking peptide intervention group was significantly longer than that of the control group (Fig. 4a, b), while their sucrose preference was significantly lower than that of the control group (Fig. 4c). These results indicate that blocking the CXCR3 peptide induced depressive-like behavior in mice. Similarly, in the EPM experiment, similar to the CRS group, the frequency of mice entering the open arm in the CXCR3-blocking peptide intervention group was significantly lower than that in the control group (Fig. 4d). There was no significant difference in the total distance traveled by mice in the open field experiment among the groups (Fig. 4e), ruling out the influence of differences in the motor abilities of mice between different groups on the experimental results. The above experimental results indicate that blocking CXCR3 can induce depressive / anxiety-like behavior in mice, to a degree similar to that of the CRS model.

[0121] 6.3 Peripheral administration of CXCL10 can cross the blood-brain barrier and enter the brain.

[0122] In vivo imaging experiments showed that after tail vein administration of Cy5.5-labeled CXCL10, red fluorescence was observed in the brain 8 hours later, indicating that the fluorescently labeled CXCL10 could cross the blood-brain barrier and enter the brain (Figure 5). These results suggest that the ameliorative effect of peripheral administration of CXCL10 on depressive-like behavior in mice may depend on its ability to act in the brain by crossing the blood-brain barrier.

[0123] The sequences used in this article are as follows:

[0124] All documents mentioned in this invention are incorporated herein by reference as if each document were individually incorporated by reference. Furthermore, it should be understood that after reading the foregoing teachings of this invention, those skilled in the art can make various alterations or modifications to this invention, and these equivalent forms also fall within the scope defined by the appended claims.

Claims

1. The use of a cytokine CXCL10, characterized in that, Used to prepare a medicine for the prevention and / or treatment of depression and / or anxiety disorders.

2. The use as described in claim 1, characterized in that, The cytokine CXCL10 has the amino acid sequence shown in SEQ ID NO:

1.

3. The use as described in claim 1, characterized in that, The drug is used for one or more purposes selected from the group consisting of: 1) Used to shorten immobility time in patients with depression and / or anxiety disorders; 2) Used to reduce the level of despair in patients with depression and / or anxiety disorders; 3) Used to improve anhedonia in patients with depression and / or anxiety disorders; 4) Used to reduce anxiety levels in patients with depression and / or anxiety disorders.

4. The use as described in claim 1, characterized in that, The administration method of the drug is selected from the following group: intravenous injection, subcutaneous injection, and nasal inhalation.

5. The use as described in claim 1, characterized in that, The dosage of the drug is 0.5-2 ng per mouse.

6. The use as described in claim 1, characterized in that, The dosage of the drug is 0.8-1.5 ng per mouse.

7. The use as described in claim 1, characterized in that, The depression and / or anxiety disorder is a depression and / or anxiety disorder with low CXCL10 expression.

8. The use as described in claim 1, characterized in that, The drug can cross the blood-brain barrier.

9. A pharmaceutical composition, characterized in that, It contains a pharmaceutically acceptable carrier and a safe and effective amount of the cytokine CXCL10.

10. Use of the pharmaceutical composition of claim 9, characterized in that, Used for the prevention and / or treatment of depression and / or anxiety disorders.

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