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Use of synaptotagmin-7 in the diagnosis and treatment of bipolar disorder

A bipolar disorder, uses technology, applied in the field of biomedicine, to solve problems that do not exhibit cycles of manic and depressive mood cycles

Active Publication Date: 2021-10-15
TSINGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these genes represent only a small fraction of clinical cases; moreover, genetic animal models based on these genes do not exhibit spontaneous cycles of manic and depressive mood, which is a core symptom in BD patients

Method used

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  • Use of synaptotagmin-7 in the diagnosis and treatment of bipolar disorder
  • Use of synaptotagmin-7 in the diagnosis and treatment of bipolar disorder
  • Use of synaptotagmin-7 in the diagnosis and treatment of bipolar disorder

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Example 1 Syt7 identified as a candidate risk factor for neuropsychiatric disease-like behavior

[0042] In order to effectively identify the contributing factors of emotional abnormalities in BD patients, we selectively observed the expression and function of some genes in neurons differentiated from iPSCs derived from BD patients. Also consider that an important feature of BD patients is that about 40% of BD patients suffer from insulin / glucose metabolism disorders (references Ruzickova M, Slaney C, Garnham J, & AldaM (2003) Clinical features of bipolar disorder with and without comorbiddiabetes mellitus.Canadian journal of psychiatry 48(7):458-461, Hajek T, McIntyre R, & Alda M(2016) Bipolar disorders, type 2diabetes mellitus, and the brain. Current opinion in psychiatry29(1):1-6, and Literature Wysokinski A, Strzelecki D, & Kloszewska I (2015) Levels of triglycerides, cholesterol, LDL, HDL and glucosein patients with schizophrenia, unipolar depression and bipolar di...

Embodiment 2

[0047] Example 2 Syt7 deficiency induces fluctuating behavioral abnormalities in mice

[0048] In order to systematically study the role of Syt7 in brain psychiatric disease-like behaviors, we first independently studied the expression of Syt7 in BD patients in neurons differentiated from two types of iPSCs from different sources. in figure 2 A and B show hippocampus from LR and NR patients recorded in Mertens J, et al. (2015) Differential responses to lithium in hyperexcitable neurons from patients with bipolar disorder. Nature 527(7576):95-99 Expression of Syt7 in neurons, where LR represents iPSC differentiated neurons that respond to lithium (lithium salt), and NR represents iPSC differentiated neurons that do not respond to lithium. figure 2 C shows the iPSC-differentiated hippocampal nerves described in the literature Stern S, et al. (2017) Neurons derived from patients with bipolar disorder divide into intrinsically different sub-populations of neurons, predicting th...

Embodiment 3

[0056] Example 3 Emotional stabilizer treatment of Syt7KO mice

[0057] In order to further determine the relationship between abnormal behavior of Syt7KO mice and BD manifestations, we treated Syt7KO mice with olanzapine (olanzapine, OLZ) and lithium, two drugs used clinically and preclinically to treat BD patients, and observed animal behavior.

[0058] First, Syt7KO mice were treated with atypical antipsychotic drug olanzapine (OLZ), and the dose-dependent relationship was observed (the doses used were 0.2, 0.5 and 1.0 mg / kg) (ANOVA statistical method was used). Such as Figure 5 As shown in A and B, moderate doses of olanzapine in drug-treated Syt7KO mice were sufficient to alter behavioral abnormalities (i.e., the relatively short immobility time of the nocturnal phase) in the FST test compared with the non-treated group. was reversed); furthermore, high-dose olanzapine treatment prolonged diurnal immobility. In addition, low-dose olanzapine treatment reduced the immobi...

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Abstract

The invention relates to the field of biomedicine, in particular to the use of Synaptotagmin-7 (Syt7) in the diagnosis and treatment of bipolar affective disorder. A biomarker for bipolar disorder is provided, the biomarker includes Syt7 gene and / or its expression product. Also provided is the use of the Syt7 gene and / or its expression product in the preparation of medicines for treating bipolar affective disorder. By monitoring the Syt7 gene and / or its expression products, it can be used to screen drugs for the treatment of bipolar disorder, and provide assistance for the diagnosis and treatment of Syt7 molecules.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to the use of Synaptotagmin-7 in the diagnosis and treatment of bipolar disorder. Background technique [0002] Bipolar disorder (BD) is a typical neuropsychiatric disease in which patients suffer from alternating episodes of mania and depression. The global incidence of BD exceeds 1%, and 15% of patients commit suicide because of lack of timely treatment. Therefore, BD is listed by the World Health Organization (WHO) as one of the diseases with the highest morbidity and labor loss rate. Clinical studies have discovered a series of susceptibility genes for BD using genome-wide association analysis. These genes were once considered to be related to the inheritance and pathogenic mechanism of BD. However, genetic animal models based on these susceptibility genes have not been able to display the clinical features of BD, especially the core symptoms of spontaneous alternating cycles of man...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12Q1/6883G01N33/68A61K38/17A61P25/18A61P25/24A01K67/027C12Q1/02A61K49/00
CPCC12Q1/6883G01N33/6893A61K38/1709A61P25/18A61P25/24A01K67/0276G01N33/5008A61K49/0008C12Q2600/158C12Q2600/118G01N2800/304G01N2800/52G01N2333/47A01K2217/075A01K2227/105A01K2267/0356C12N2503/02G01N2500/10G01N33/5023G01N33/5088C12Q2600/136A01K2267/0306A01K2217/058A61K31/5513A61K33/00G01N2333/705
Inventor 姚骏沈伟王秋文刘要南
Owner TSINGHUA UNIV