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Pharmaceutical composition for specifically regulating activity of hypothalamic ventral nucleus astrocyte and application of pharmaceutical composition

A technology of astrocytes and compositions, applied in the field of biomedicine, can solve the problems of excitotoxicity, stimulation, physical damage, etc., and achieve the effect of unique practicability, long onset time and small damage

Pending Publication Date: 2021-10-01
SHENZHEN INST OF ADVANCED TECH CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, it is well known that stimulating neurons for a long time may cause excitotoxicity; while stimulating for too short a time, differences in anxiety behavior and bone metabolism may not be seen
In addition, optogenetics technology needs to embed optical fibers in the brain for light stimulation, and the surgical process will cause great physical damage

Method used

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  • Pharmaceutical composition for specifically regulating activity of hypothalamic ventral nucleus astrocyte and application of pharmaceutical composition
  • Pharmaceutical composition for specifically regulating activity of hypothalamic ventral nucleus astrocyte and application of pharmaceutical composition
  • Pharmaceutical composition for specifically regulating activity of hypothalamic ventral nucleus astrocyte and application of pharmaceutical composition

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] Embodiment 1 constructs mouse anxiety model

[0055] C57BL / 6 or S100β-Cre mice were subjected to unpredictable environmental stress stress once a day for 4-8 weeks to induce mouse anxiety models.

[0056] Environmental stress stress stimuli include the following three ways:

[0057] a) Four mice were placed in a relatively narrow box (3cm×5cm×7cm) for 2 hours of crowded stress stimulation;

[0058] b) placing the mouse in a wet litter cage for 6 hours;

[0059] c) Put the mice on a transparent platform with a height of 100 cm for 2 hours.

[0060] The three environmental stress modes were randomly selected by the experimenter before the experiment to reduce the adaptability of the mice.

[0061] After the modeling was completed, open field and elevated plus-maze tests (EPM) were performed to verify the anxiety level of the animals to confirm whether the modeling was successful.

[0062] Among them, the open field maze is mainly composed of an empty box with a bottom...

Embodiment 2

[0070] Example 2 Chronic stress stress induces symptoms of anxiety and bone loss, and stimulates astrocytes in the VMH brain area

[0071] (1) Put the perfused animal or the separated leg bone into the Medikors Small Animal Body Composition Analyzer (InAlyzer), and perform bone density scanning analysis on the samples of the dual-energy X-ray animal body composition analysis system:

[0072] Place the sample on the same horizontal plane and in the same direction for dual-energy X-ray scanning analysis;

[0073] After scanning, a 5mm × 5mm area of ​​interest was uniformly drawn to analyze and calculate the bone density of the samples, and the statistical analysis of the differences in bone density among the groups was performed using prism software.

[0074] Such as image 3 As shown, the I picture is the X-ray bone density imaging result, and the II picture is the bone density statistical result;

[0075] Figure 4 It is the H&E comparison chart of bone tissue, in which the...

Embodiment 3

[0079] Example 3 Using pharmacogenetics to activate the Gi signaling pathway in VMH astrocytes

[0080] In order to verify the regulatory role of VMH astrocytes in anxiety and bone loss, the pharmacogenetic element hM4Di was used to selectively activate the Gi pathway of astrocytes in this example.

[0081] In this example, in order to selectively activate the Gi pathway in astrocytes in the VMH, 500 nL of AAV-DIO-hM4Di-mCherry (10 13 gc / mL); the control group was injected with AAV-DIO-mCherry (10 13 gc / mL);

[0082] Give the mice a recovery time of 4 weeks after the operation to ensure the complete expression of the virus;

[0083]After the virus expression was complete, the mice were injected intraperitoneally with clozapine nitrogen oxide (Clozapine N-oxide, CNO, 1 mg / kg) three times a week, and the control group was injected with the same amount of normal saline, and these mice were Perform chronic stress stress stimulation;

[0084] To observe the effect of selectivel...

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Abstract

The invention provides a pharmaceutical composition for specifically regulating activity of hypothalamic ventral nucleus astrocytes and application of the pharmaceutical composition. The pharmaceutical composition comprises clozapine nitrogen oxide and a viral vector used for infecting the astrocytes; the viral vector comprises a pharmaceutical genetics regulatory element hM4Di or hM3Dq. The pharmaceutical composition can selectively activate a Gi pathway or a Gq pathway of astrocytes, and by means of the pharmaceutical composition. According to the invention, it is proved that anxiety-like behaviors and bone loss phenomena induced by chronic pressure stress can be intervened by selectively adjusting the activity of VMH astrocytes.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and specifically relates to a pharmaceutical composition for specifically regulating the activity of astrocytes in the ventromedial nucleus of the hypothalamus and an application thereof. Background technique [0002] Research evidence shows that nervous system function and bone metabolism are interrelated. Combined with a large amount of experimental data, some researchers have proposed that all organs maintain the overall physiological function balance through organ talk; bone growth, metabolism and remodeling are regulated by multiple organs in the body, and bone metabolism itself also affects It affects the function of several vital organs including the brain, gonads and digestive system. [0003] In addition, a large number of research data show that anxiety and depression are closely related to bone loss, but the underlying mechanism is still unclear. And through case correlation anal...

Claims

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Application Information

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IPC IPC(8): A61K31/551A61K48/00A61K9/00A61P25/22A61P19/10
CPCA61K31/551A61K48/005A61K48/0008A61K9/0019A61K9/0053A61K9/0085A61P25/22A61P19/10A61K2300/00
Inventor 刘运辉杨帆邵杰
Owner SHENZHEN INST OF ADVANCED TECH CHINESE ACAD OF SCI
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