Depression-mental disorders-Brain Case ()

The neurological issue affecting hundreds of millions of young people globally: Depression

Depression, manifested as persistent low spirits and mood disorders, is one of the most common and prominent mental disorders worldwide. Globally, years lost to disability (YLD) due to disability caused by depression is as high as 76.4 million, accounting for 10.3% of all disease burden YLD, ranking first among disease burden factors. About 350 million people around the world suffer from depression, and the incidence rate in China is about 3.02%, and researchers believe that due to the impact of diagnosis methods, Chinese people's depression is far underestimated[1] . Its typical symptoms mainly include depression, slow thinking, loss of interest, eating and sleeping disorders, cognitive impairment and various other physical symptoms [2].

Despite this, we still know little about the etiology and pathogenesis of depression. Depression is not a simple functional mental disorder, but a disease involving genetic, psychological, biochemical and social environment factors[3-4] Based on this, hypotheses explaining the pathogenesis of depression from different perspectives have also been formed, such as the monoamine neurotransmitter hypothesis (that depression is related to the lack of neurotransmitters such as serotonin), and the neuroplasticity hypothesis (that neuroplasticity disorders eventually lead to depression), etc. The hypotheses have different entry points and pathogenic mechanisms, but they all provide the possibility to explain the pathogenesis of depression.

In order to study the development and mechanism of depression, after continuous exploration, researchers have constructed a scientific and effective animal model of depression as the in vivo research basis for basic research on depression. Depression model animals show behavioral changes such as depression and cognitive dysfunction, which can simulate human depression symptoms. The use of animal models can not only circumvent the ethical issues of human depression research, but also obtain sufficient sample size for research. Therefore, animal models of depression have become an important tool for depression research [5].

Animal models of depression

Over the years, in order to accurately simulate the occurrence and symptoms of depression, researchers have carried out in-depth research on animal models of depression in terms of environmental stress, social stress, neurobiochemistry, and genetic modification. The entry point of each model is different, and each has its own scope of application and limitations. The modeling methods of depression can be divided into four categories, namely, stress modeling, surgical modeling, and drug-induced modeling. modeling and genetic modeling.

	Model Name	Modeling Method	Advantages/ Disadvantages
Stress modeling	Forced swimming test，FST	Rats or mice are placed in a limited and inescapable space to swim, and when escape fails for many times, they give up struggling and float on the surface of the water in a state of "desperate".	This method is simple and easy to implement, and can be used for primary screening of antidepressants with high reliability. However, this model has false positive reactions, and there are large differences in strains.
	Tail suspension test，TST	Hanging the head of the animal downwards, in order to overcome the abnormal position, the animal will not get out of the predicament after many struggles, and then intermittently does not move, showing the state of "desperate behavior".	This method is a behavioral method with high sensitivity in the screening of antidepressant drug activity, and because it is fast and convenient, but the model also has strain differences and may be more suitable for the establishment of an acute stress depression model.
	Learned helplessness model, LH	After repeatedly giving uncontrollable vicious stimuli, it shows the lack of escape behavior and other phenomena.	Controversial: There is no evidence that the clinical symptoms of patients with depression are due to the psychological process of learned helplessness.
	Chronic social defeated stress, CSDS	This is achieved by using conflicts between the same species to generate mental and psychological pressure.	This model can induce behavioral manifestations of depression and anxiety at the same time, and may be more suitable for the study of mechanisms with mixed characteristics of the two.
	Chronic restraint stress，CRS	The chronic restraint stress model consists of repeatedly placing rodents in restraint tubes and restricting their freedom of movement for a period of time.	This kind of model is easy to make, and it is often combined with chronic mild stress model in experiments. This model is widely used to study changes in morphology, hormone levels and behavior of different brain regions in rodents.
Surgical modeling	Olfactory bulbectomized , OB	The olfactory bulbs are located in the front of the telencephalon. Removal of bilateral olfactory bulbs in rats produces complex behaviors, so it is also a very effective model for simulating human depression.	This model has obvious depressive effects and good reliability, and is often used for secondary screening and mechanism research of antidepressants. However, the requirements for experimental surgical techniques are high, the mortality rate of animals in the experiment is high, and the models have strain differences.
Surgical modeling	Post-stroke depression , PSD	An animal model of post-stroke depression combined with middle cerebral artery occlusion and spatial behavioral restriction	This model ideally simulates the depression state of clinical stroke patients due to limb paralysis and limited movement, and provides a basis for the pathological mechanism research and clinical treatment of post-stroke depression.
Drug-induced modeling	Reserpine drug model	Such models are mainly based on the monoamine hypothesis of depression, such as the reserpine-induced depression model	This type of model mainly screens antidepressants for specific targets. It can be used to explore the pharmacological properties of antidepressants, or to screen unknown compounds.
Genetic modeling	Flinders sensitive rat line, FSL	Overstreet and Wegener[6] initially discovered the rat model.	The behavioral performance, neurochemical and pharmacological mechanisms of this model rat are similar to those of patients with depression, and it is a very effective animal model for testing antidepressants.
Genetic modeling	Wistar·Kyoto, WKY	Nam et al. [7] found this animal model.	This strain of rats is derived from spontaneously hypertensive rats, which can show similar hormone levels, behavioral and physiological abnormalities as those of patients with depression.

Literature citation
[1] Smith K. Mental health: a world of depression [J]. Nature,2014, 515(7526):181.
[2] Kupfer D J, Frank E, Phillips M L. Major depressive disorder：new clinical, neurobiological, and treatment perspectives [J] Lancet, 2012,379： 1045-1055.
[3] Fischer AS, Camacho MC, Ho TC, et al. Neural markers of resilience in adolescent females at familial risk for major depressive disorder[J]. JAMA Psychiatry ,2018,75 (5) :493-502.
[4] Malhi GS, Mann JJ. Depression [J]. Lancet , 2018 ,392 (10161): 2299-2312.
[5] Harro J. Animal models of depression: pros and cons[J]. CellTissue Res, 2019, 377(1):5-20.
[6] Overstreet D H , Wegener G. The flinders sensitive line rat model of depression-25 years and still producing [ J ]. Pharmacological Reviews, 2013,65：143-155.
[7] Nam H , Clinton S M , Jackson N L, et al. Learned helplessness and social avoidance in the Wistar-Kyoto rat [ J ]. Front Behav Neurosci, 2014,8：109.

One-stop service

In the field of drug efficacy and pharmacological evaluation related to neurological diseases, Brrain Case can provide you with a one-stop platform for evaluating the behavior of animals from the gene molecular level to the cell tissue level, to the neural circuit, and finally to the animal as a whole.

At the gene molecular level, through gene editing, gene interference, in situ hybridization, immunohistochemistry and other technical means, verify the influence of genes or proteins on cell physiological metabolic signal transduction, gene expression regulation, etc. Experimentally verify the function of a molecule.

At the neural circuit level, we can analyze the structure and function of neural circuits formed between different brain regions and different types of neurons by means of circuit tracing, optogenetics, chemical genetics, and electrophysiology. Such research is one of the key development directions of neuroscience at present. Understand, manipulate and analyze the dramatic phenotypic differences brought about by changes in neuronal connectivity.

At the same time, Brain Case also provides a high-precision animal behavior testing platform after neurological disease modeling, including but not limited to: cognitive function testing, motor function testing, multi-channel in vivo electrophysiological recordings of awake animals, respiratory recordings, auditory, Pain, anxiety, depression, behavioral tests related to olfactory function, etc.

MRI/fMRI/PET-CT small animal living imaging, cardiac ultrasound, X-ray film, tissue fluorescence imaging (whole brain slide scanning, tissue immunofluorescence imaging), calcium imaging, and confocal two-photon imaging can also be provided.