BCG and PTX Combined Induction for Stable Depression Models
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for constructing depression animal models using Bacille Calmette-Guerin (BCG) require high doses, leading to increased costs and short duration of depression-like behaviors, which are not easily distinguished from pathological behaviors, making them unstable and costly for pharmacological experimental models.
Innovation Solution
A method involving the combined induction of BCG and pertussis toxin (PTX) in mice, where BCG is diluted to a lower colony-forming unit concentration and PTX is administered over several days to induce long-acting depression-like behaviors, reducing the overall cost and duration of the model.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If high dose BCG is used to induce depression model, then the model stability and duration are improved, but the cost increases significantly
Solution Approach 1:
The patent combines BCG with PTX to create a composite induction model. This merging of two substances allows the use of lower BCG doses (1×10^5 to 5×10^6 CFU/mouse) while maintaining model stability and extending depression-like behavior duration, thereby reducing BCG cost without sacrificing model reliability
Solution Approach 2:
The invention uses a composite approach by combining BCG (bacterial component) with PTX (toxin component) to create a synergistic induction system. This composite model achieves prolonged depression-like behaviors and improved stability at reduced BCG dosage, effectively resolving the contradiction between model reliability and substance quantity
2Duration of action of moving object
If high dose BCG is used to induce depression model, then the duration of depression-like behaviors is extended, but the cost of modeling increases
Solution Approach 1:
By merging BCG with PTX in a combined induction protocol, the patent achieves extended duration of depression-like behaviors (lasting from 2 weeks to several months) while using significantly reduced BCG doses. The PTX component appears to prolong the behavioral effects without requiring high BCG quantities
Solution Approach 2:
The invention changes the dosing parameters by using low-dose BCG (1×10^5 to 5×10^6 CFU/mouse) combined with PTX administrations at days 0, 1, and 2. This parameter modification achieves prolonged depression-like behaviors while reducing BCG consumption and associated costs
3Reliability
If high dose BCG is used to induce depression model, then the model is more stable, but the cost of constructing the model increases greatly
Solution Approach 1:
The patent merges BCG with PTX to create a cost-effective induction model. The combination allows construction of stable depression models using lower BCG doses, thereby reducing the overall cost of model construction while maintaining reliability for pharmacological experiments
Solution Approach 2:
The invention employs a strategy of using smaller quantities of expensive BCG by combining it with PTX, effectively replacing part of the BCG requirement with a more cost-effective alternative that achieves the same model stability at lower cost
Data Source
AI summary
The present disclosure provides a kit and method for constructing a long-acting depression animal model. The present disclosure adopts Bacille Calmette-Guerin (BCG) (or Mycobacterium bovis (M bovis)) and low-dose pertussis toxin (PTX) for combined induction, which greatly reduces modeling cost. A mouse model constructed by the method of the present disclosure can clearly distinguish a time interval of pathological behaviors from a time interval of depression-like behaviors and has prominent face validity and predictive validity. The method of the present disclosure is simple and convenient and does not require a large number of tedious daily operations as the depression model construction by chronic unpredictable stress, chronic restraint stress, social defeat, mother-child separation, or the like. The mouse model of the present disclosure can provide a valuable long-term intervention window for research on antidepressant therapy.