CN115350172A

CN115350172A - Application of Gabapentinin in AD scene memory improvement

Info

Publication number: CN115350172A
Application number: CN202211125119.2A
Authority: CN
Inventors: 甘平; 胡炜彦; 付朝江; 彭福基; 杨颖颖; 谢太玉; 徐洁; 周朝香; 刘芸君; 李璐明
Original assignee: Kunming Medical University
Current assignee: Kunming Medical University
Priority date: 2022-08-12
Filing date: 2022-09-14
Publication date: 2022-11-18

Abstract

The invention discloses an application of Gabapentin in improving AD scene memory, which comprises the application of an APP/PS1 Alzheimer disease animal model as an application model, a wild mouse is used as a control group, and Gabapentin granules are dissolved by normal saline and used in an intraperitoneal injection mode: the dosage of single administration is 50mg/kg, the administration is carried out 7 days per month, and then the behavioral detection is carried out. And detecting and analyzing the result of practical application to obtain the description of the effect of the Gabapentin on the AD scene memory improvement. The medicine is injected into the abdominal cavity, so that the overexcitement of neurons can be reduced, the situation memory function of an AD mouse is improved, a new use method of Gabapentin is expanded, and a new idea is provided for the treatment of AD.

Description

Application of Gabapentinin in AD scene memory improvement

Technical Field

The invention belongs to the technical field of medicine application, and particularly relates to application of Gabapentin in improving AD scene memory.

Background

Alzheimer's Disease is also called senile dementia, english name Alzheimer's Disease is abbreviated as AD, the AD is a progressive neurodegenerative Disease, the main clinical symptoms of the AD are aphasia, learning and memory disorder, agnosias, serious mental problems possibly occur in the later period of Disease onset, the learning and memory disorder is one of the main symptoms of AD, a method capable of effectively treating the learning and memory disorder is not found at present, the contextual memory is used as an important memory mode of learning and memory and is the basis of learning and cognition, data show that the disorder of contextual memory occurs in AD patients and animal models, gabapentin (Gabapentin) is used as a second-line medicine for resisting epilepsy and has the effects of analgesia, anticonvulsion, post-stroke treatment and the like, but no research reports that the Gabapentin can be used for treating the related symptoms of AD at present, the effect of treating the epilepsy is used for solving the problem of abnormal excitation of neurons, the specific mechanism of the Gabapentin is acted on a receptor alpha 2 delta on a calcium ion channel, 20% of the AD patients and the animal models have 20% of the related symptoms of the AD, the epilepsy, the AD is used for treating the abnormal excitation of the neuronal excitation, and the neuronal hyperexcitability of the AD in the animal models, and the neuronal hyperexcitability is an important mechanism for treating the AD, thus the AD is a neuron for treating the AD in the cognitive neuronal hyperexcitability of the AD.

Disclosure of Invention

The invention aims to provide application of Gabapentin to AD scene memory improvement and aims to solve the problems in the background technology. In order to realize the purpose, the invention adopts the technical scheme that:

the application of the Gabapentin to the AD scene memory improvement comprises that the applied model is an APP/PS1 Alzheimer disease animal model, a wild mouse is used for a control group, and the Gabapentin granules are dissolved by normal saline and used in an intraperitoneal injection mode: the dosage of single administration is 50mg/kg, the administration is carried out 7 times per month, and then the behavioral detection is carried out. And detecting and analyzing the result of practical application to obtain the description of the effect of the Gabapentin on the AD scene memory improvement.

The invention has the beneficial effects that: the invention discloses application of Gabapentin in improving AD situation memory, and by adopting the medicine disclosed by the invention for intraperitoneal injection, the overexcitation of neurons can be reduced, the AD mouse situation memory function can be improved, a new application method of Gabapentin is expanded, and a new thought is provided for treating AD.

Drawings

FIG. 1 is a graph showing the results of a fear memory test on the background before administration to mice of 11 to 12 months of age;

FIG. 2 is a graph showing the results of a fear-box experiment on mice administered 12-13 months of age-one month later;

FIG. 3 is a graph showing the results of a fear box experiment in mice administered two months after 11-12 months of age;

Detailed Description

In order that the invention may be more fully understood, reference will now be made to the accompanying examples. The preferred embodiments of the present invention are given in the examples. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.

The technical solution of the present patent will be described in further detail with reference to the following embodiments.

The embodiment of the invention provides an improvement experiment of Gabapentinin on AD scene memory

Animal grouping:

the APP/PS1 model mouse is 20 mice, the month of age is between 11 months and 12 months, and the mice with the age of more than 10 months are defined as aged mice. 10 males and females are divided into two groups, one group is used as a solvent control group, the other group is used as an experimental group (the concentration of Gabapentinin is 50 mg/kg), and each group is provided with 5 females and males; wild Type mice, i.e., wild Type mice, were divided into groups of 5 males and females, respectively, to make a WT control group.

The experimental steps are as follows:

the method comprises the steps of carrying out intraperitoneal injection on 0.9% physiological saline in a WT control group, carrying out intraperitoneal injection on 0.9% physiological saline in a solvent control group, carrying out intraperitoneal injection on mice in the WT control group and the solvent control group according to 100ul physiological saline/10 g of body weight, carrying out intraperitoneal injection on Gabapentin in an experimental group, uniformly mixing the Gabapentin with the 0.9% physiological saline, vibrating and dissolving the Gabapentin, wherein the administration concentration of each mouse is 50mg/kg, the administration volume is 100ul/10g of body weight, preparing the medicine in a present preparation manner, carrying out a background fear memory experiment detection baseline for 4 days before administration, carrying out rest for 19 days after continuous administration of the mice for 7 days, carrying out a background fear memory experiment after administration after 19 days, carrying out rest for 7 days, and repeating the experiment steps. Statistical analysis was performed using Graphpad principles software.

Background fear memory test:

introduction to the experiment

The conditional fear experimental system (scene fear system) is used for environmental-related conditional fear experimental study of small rodents (big and mouse). Rodents exhibit a characteristic immobility state (Freezing) upon fear, in which case the animals tend to remain in a stationary defensive posture. During the experiment, the subject was given an acoustic signal (conditional stimulus) followed by an electric shock (unconditional) stimulus. The training is called conditional training, and after the training is finished, the experimental animal carries out sound signal or environment connectivity experiment. Rodents typically respond to the same acoustic signature in both the corresponding environment and in different environments with significant conditioned fear, such as standing still. Such tests may be performed immediately or several days after the training is complete and may provide information on short-term and long-term memory under the influence of a conditioned signal.

The training device is mainly 30x24x21cm ³ The box has 18 stainless steel round bars with the diameter of 4mm at the bottom, and generates certain current under set conditions, wherein a box door is provided with a camera, a computer is connected, the electric shock response can be recorded and analyzed by software, and the immobility time (MED-associates St Albans. VT) is analyzed.

Fear memory test, comprising three parts:

(1) the method is suitable for the following steps: i.e. an advance exposure of the scene. The test mice were placed in the test chamber and allowed to move freely for 5min to eliminate the effects of the novel environment.

(2) Training: after 24 hours of adaptation, the mice are placed in the same test box for training, the training time is 12 minutes each time, electric shock is given every 2 minutes, 30 seconds of continuous sound stimulation is given before the electric shock, each electric shock lasts for 2 seconds, the strength is 0.8mA, the electric shock is given for 5 times in total, and after each electric shock, the system records the immobility time as a detection index of fear memory.

(3) And (3) testing: recording the time point of training completion, taking the time as reference, after 2h,24h and 72h, putting the mouse into the same test box again, freely moving for 180s, giving 180s continuous sound stimulation, testing the fear degree of the mouse on the sound, and recording the immobility time of the mouse at the end. "

Statistical methods figure 1 parameter pairing T-test, figure 2 and figure 3 using one-way anova, and Tukey's multiple complexes test between groups.

The upper panel of FIG. 1 is a fear box test before administration of 10 WT mice of 11 to 12 months of age and 20 mice of APP/PS1 of 11 to 12 months of age, the left panel is a group of mice, pre of Training (Training) stage, 1,2,3,4,5 are values of the group of mice after the percentage of the Time of immobility (Freezing Time) to 120s is rounded, AV is an average value, SEM is a standard error of the average value, and the Training (Training) stage is to test the learning ability of the mice. 2h,24h,72h in the Test (Test) phase are different memory Test phases, 2h is testing short-term memory, and 24h and 72h are testing long-term memory. 2h,24h,72h correspond to the values of the group of mice in which the Time of immobility (Freezing Time) is a percentage of the Time of 360s, and the values are rounded up, AV is the mean value, SEM is the standard error of the mean value, and the Test phase is the memory extraction phase. AD mice memory phase of right figure 72h exhibited dysmnesia compared to WT and statistical parameter paired T-test showed p <0.05, significant difference in both groups.

Fig. 2 shows the results of the fear box experiment after three groups of 12-13 month old mice are administered for one month, the memory extraction stage of the experiment, the long-term memory and the short-term memory of the AD Gabapentin administration group mice are close to that of the WT solvent group (saline), and the results prove that the memory of the experiment group is close to that of the WT group after one month administration, and the drug plays a certain role.

Fig. 3 shows the results of the fear box experiment after three groups of 13-14 month old mice were administered one month, the memory extraction stage (Test) of the experiment, the Gabapentin administration group for AD, i.e., the AD 50mg/kg group in the figure, and the long-term memories of 24h and 72h were improved compared with the adaline group, i.e., the AD solvent control, and the number of mice was sufficient, and although statistically no significant difference occurred, the trend was very significant, and compared with other groups, the Gabapentin intraperitoneal injection could indeed improve the situation memory ability.

The above embodiments are only for illustrating the invention and are not to be construed as limiting the invention, and those skilled in the art can make various changes and modifications without departing from the spirit and scope of the invention, therefore, all equivalent technical solutions also belong to the scope of the invention, and the scope of the invention is defined by the claims.

Claims

Application of gabapentin to AD contextual memory improvement.