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Method and kit for diagnosing depression

A technology for depression and kits, applied in the field of disease diagnosis, can solve problems such as increasing the risk of severe depression

Active Publication Date: 2018-11-13
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Cannabinoid receptor antagonist drugs such as rimonabant do work well in treating obesity but may increase the risk of major depressive disorder in users

Method used

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  • Method and kit for diagnosing depression
  • Method and kit for diagnosing depression
  • Method and kit for diagnosing depression

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0056] Embodiment 1 Materials and methods

[0057] Virus

[0058] To achieve selective photoactivation or photoinhibition of BLA CCK glutamatergic neurons, the BLA of CCK‐ires‐Cre mice was injected with AAV2 / 9‐CaMKIIα‐Cre on‐ChR2(H134R)‐mCherry virus (viral titer : 4.5×10 12 particles / mL), or AAV2 / 9‐CaMKIIα‐Cre on‐Arch3.0‐eYFP virus (virus titer: 3.6×10 12 particles / mL). In order to achieve chemogenetic activation or inhibition of BLA CCK glutamatergic neurons, the BLA of CCK‐ires‐Cre mice was injected with AAV2 / 9‐CaMKIIα‐Cre‐on‐hM3Dq‐mCherry virus (virus titer: 3.5 ×10 12particles / mL), or AAV2 / 9‐CaMKIIα‐Cre on‐hM4Di‐mCherry virus (virus titer: 2.2×10 12 particles / mL).

[0059] To achieve selective photoactivation or photoinhibition of BLA non-CCK glutamatergic neurons, the BLA of CCK‐ires‐Cre mice was injected with AAV2 / 9‐CaMKIIα‐Cre out‐ChR2(H134R)‐eYFP virus (viral titer Degree: 1.8×10 12 particles / mL) or AAV2 / 9‐CaMKIIα‐Cre out‐Arch3.0‐eYFP virus (virus titer: 3.6×1...

Embodiment 2

[0110] Example 2 Cholecystokinin CCK as a marker of amygdala glutamatergic neurons subdividing mediating opposite emotional valences

[0111]To visualize CCK-expressing neurons in the amygdala, mice expressing Cre recombinase under the cholecystokinin promoter (CCK-ires-Cre) and Cre-dependent expression of tdTomato (tdT) reporter mice (Ai14-LSL ‐tdT) for hybridization ( figure 1 a). CCK-positive neurons were predominantly distributed rostral to caudal to the basolateral amygdala BLA rather than the central amygdala (CeA) (figure 1b).

[0112] To test whether CCK-positive neurons in the BLA are also inhibitory GABAergic neurons, immunofluorescence ( figure 1 c) To detect (1) glutamic acid decarboxylase 1 (GAD 67), a marker of inhibitory GABAergic neurons; (2) parvalbumin (PV), a marker of GABAergic neuron subtypes; (3) growth inhibitory (SOM), a marker for GABAergic neuron subtypes; and (4) CaMKIIα, a marker for excitatory glutamatergic neurons. Surprisingly, it was found t...

Embodiment 3

[0114] Example 3 Cholecystokinin-positive neurons and negative neurons projecting to the nucleus accumbens mediate opposite emotional valences, respectively

[0115] To test whether parallel cholecystokinin-positive glutamate neuron and cholecystokinin-negative glutamate neuron circuits from BLA to NAC mediate similar or different behavioral phenotypes, respectively, the aforementioned Cre-on and Cre The ‐out strategy selectively activates cholecystolin-positive or cholecystin-negative glutamatergic neurons and is validated in real-time light-evoked place preference or place aversion experiments. Unexpectedly, optogenetic activation of cholecystin-positive glutamatergic neurons projecting to the nucleus accumbens when selectively administered to one side of the two-box experiment resulted in a decrease in the time mice spent on this one ( figure 1 i, l), which shows that activation of this circuit produces behavioral aversion. In order to confirm this behavioral aversion, dur...

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Abstract

The invention provides a method for diagnosing depression, which comprises the detection of a glutamate acid neural signal in a patient's nucleus accumbens loop, and particularly comprises the detection of a cannabinoid systemic neural signal in the patient's basolateral amygdala-nucleus accumbens loop, for example, the detection of the amount of a type 1 cannabinoid receptor (a CB1 receptor) in cholecystokinin-positive glutamate neurons of the basolateral amygdala. The invention further provides a kit for diagnosing the depression, which comprises a reagent for detecting a glutamate systemicneural signal of the nucleus accumbens loop, in particular the reagent for detecting the cannabinoid systemic neural signal in the basolateral amygdala-nucleus accumbens loop, for example, the reagentfor detecting the amount of the type 1 cannabinoid receptor (the CB1 receptor) in the cholecystokinin-positive glutamate neurons of the basolateral amygdala.

Description

technical field [0001] The invention relates to the field of disease diagnosis. Specifically, the present invention relates to diagnostic methods and kits for depression. Background technique [0002] Depression is a highly prevalent psychiatric disorder that may trigger a variety of dysfunctions including behavioral hopelessness and social avoidance. External stress can lead to changes in the neuroplasticity of the brain's reward and aversion systems. And this change in plasticity plays an important role in the formation and development of depression. There are many brain regions involved in the encoding of emotional valence, and the basolateral amygdala (BLA) is one of the important brain regions. This brain region is known to play an important role in the emotion of fear and anxiety, according to current research. [0003] A major downstream of the BLA is the nucleus accumbens (NAc). Current research suggests that the NAc is involved in various affective processes su...

Claims

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Application Information

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IPC IPC(8): G01N33/94G01N33/68G01N33/577C12Q1/686
CPCC12Q1/686G01N33/577G01N33/68G01N33/9413G01N2333/70571G01N2800/304C12Q2521/107
Inventor 沈晨杰郑迪李晓明
Owner ZHEJIANG UNIV
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