mPFC-Notch1 signaling mediates METH-induced mental disorders through Hes1 inhibition of GABAB1 receptor expression

METH is a widely abused stimulant drug with strong addictive properties and high dose or long-term use of METH induces psychotic disorder (MIP)

Figure 1: Thesis map

The highly conserved Notch signaling pathway is involved in the development and differentiation of stem cells

Figure 2: Notch1 signaling pathway is specifically downregulated in mPFC of METH-sensitized mice

02 In the next study, the researchers injected the Notch1 signaling pathway inhibitor DAPT into the mPFC of mice and found that DAPT alleviated anxiety-like symptoms in METH mice

Figure 3: Differential expression of Notch1 signaling in mPFC can regulate MIP behavior

03 The dysregulation of mPFC neuronal activity is a key factor in causing MIP

Figure 4: Downregulation of NICD in mPFC attenuates neuronal activity in sensitized mice

Figure 5: Notch1 signaling negatively regulates GABAB1 receptor expression in mPFC

Figure 6: Notch1 signaling directly regulates GABAB1 receptor expression via Hes1

06 Finally, the researchers simultaneously modulated the activity of Notch1 and GABAB receptors in mouse mPFC and tested METH sensitization behavior

Figure 7: Notch1 signaling modulates METH-induced motor deficits through GABAB1 receptors

Summarize

Using a METH-induced rodent exercise sensitization model, the authors found that Notch1 signaling was downregulated in the medial prefrontal cortex (mPFC) of sensitized mice

advantage:

• Avoid the coordinate error caused by the implantation of multiple pins, and the experimental results are more accurate;

• Unified optical path to avoid signal crosstalk;

• Reduce line connections and easily improve experimental efficiency

  
  

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