The Chinese Herbal Formula PAPZ Ameliorates Behavioral Abnormalities in Depressive Mice

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Abstract

Major depressive disorder (MDD) is a chronic mental disorder characterized by mixed symptoms and complex pathogenesis. With long history of practical application, traditional Chinese medicine (TCM) offers many herbs for the treatment and rehabilitation of chronic disease. In this study, we developed a modified Chinese herbal formula using Panax ginseng, Angelica Sinensis, Polygala tenuifolia Willd, and Ziziphi spinosae Semen (PAPZ), based on an ancient TCM prescription. The antidepressant effects of PAPZ were investigated with a corticosterone (CORT) model of depression in mice. Our results showed that administration of PAPZ ameliorated depression-like phenotypes in the CORT model. An anatomic study showed that chronic PAPZ administration upregulated the protein expression of brain-derived neurotrophic factor (BDNF) in hippocampal tissue. The enzyme activity of superoxide dismutase was enhanced in hippocampal tissue, in line with a decreased malondialdehyde level. Taken together, these findings suggested that PAPZ has therapeutic effects in a mice depression model through increasing protein expression of BDNF and improving the anti-oxidation ability of the brain.

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A neurotrophic model for stress-related mood disorders.

Ronald S. Duman, Lisa M. Monteggia (2006)

There is a growing body of evidence demonstrating that stress decreases the expression of brain-derived neurotrophic factor (BDNF) in limbic structures that control mood and that antidepressant treatment reverses or blocks the effects of stress. Decreased levels of BDNF, as well as other neurotrophic factors, could contribute to the atrophy of certain limbic structures, including the hippocampus and prefrontal cortex that has been observed in depressed subjects. Conversely, the neurotrophic actions of antidepressants could reverse neuronal atrophy and cell loss and thereby contribute to the therapeutic actions of these treatments. This review provides a critical examination of the neurotrophic hypothesis of depression that has evolved from this work, including analysis of preclinical cellular (adult neurogenesis) and behavioral models of depression and antidepressant actions, as well as clinical neuroimaging and postmortem studies. Although there are some limitations, the results of these studies are consistent with the hypothesis that decreased expression of BDNF and possibly other growth factors contributes to depression and that upregulation of BDNF plays a role in the actions of antidepressant treatment.

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The tail suspension test as a model for assessing antidepressant activity: review of pharmacological and genetic studies in mice.

John F. Cryan, Cedric Mombereau, Annick Vassout (2005)

Since its introduction almost 20 years ago, the tail suspension test has become one of the most widely used models for assessing antidepressant-like activity in mice. The test is based on the fact that animals subjected to the short-term, inescapable stress of being suspended by their tail, will develop an immobile posture. Various antidepressant medications reverse the immobility and promote the occurrence of escape-related behaviour. This review focuses on the utility this test as part of a research program aimed at understanding the mechanism of action of antidepressants. We discuss the inherent difficulties in modeling depression in rodents. We describe how the tail suspension differs from the closely related forced swim test. Further, we address some key issues associated with using the TST as a model of antidepressant action. We discuss issues regarding whether it satisfies criteria to be a valid model for assessing depression-related behavioural traits. We elaborate on the tests' ease of use, strain differences observed in the test and gender effects in the test. We focus on the utility of the test for genetic analysis. Furthermore, we discuss the concept of whether immobility maybe a behavioural trait relevant to depression. All of the available pharmacological data using the test in genetically modified mice is collated. Special attention is given to selective breeding programs such as the Rouen 'depressed' mice which have been bred for high and low immobility in the tail suspension test. We provide an extensive pooling of the pharmacological studies published to date using the test. Finally, we provide novel pharmacological validation of an automated system (Bioseb) for assessing immobility. Taken together, we conclude that the tail suspension test is a useful test for assessing the behavioural effects of antidepressant compounds and other pharmacological and genetic manipulations relevant to depression.

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Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments.

M Nibuya, S Morinobu, RS Duman (1995)

The influence of chronic electroconvulsive seizure (ECS) or antidepressant drug treatments on expression of brain-derived neurotrophic factor (BDNF) and its receptor, trkB, was examined by in situ hybridization and Northern blot. In frontal cortex, acute ECS increased BDNF mRNA approximately twofold, an effect significantly augmented by a prior course of chronic ECS treatment (10 d). In the hippocampus, the influence of chronic ECS varied between the major subfields. In the dentate gyrus granule cell layer, chronic ECS decreased the acute induction of BDNF and trkB mRNA by approximately 50%, but prolonged their expression: levels remained elevated two- to threefold 18 hr later after the last chronic ECS treatment, but returned to control 18 hr after acute ECS. In CA3 and CA1 pyramidal cell layers, chronic ECS significantly elevated the acute induction of BDNF, and tended to prolong the expression of BDNF and trkB mRNA. A similar effect was observed in layer 2 of the piriform cortex, where chronic ECS significantly increased the acute induction and prolonged the expression of BDNF and trkB mRNA. Chronic (21 d), but not acute (1 d), administration of several different antidepressant drugs, including tranylcypromine, sertraline, desipramine, or mianserin, significantly increased BDNF mRNA and all but mianserin increased trkB mRNA in hippocampus. In contrast, chronic administration of nonantidepressant psychotropic drugs, including morphine, cocaine, or haloperidol, did not increase levels of BDNF mRNA. Furthermore, chronic administration of ECS or antidepressant drugs completely blocked the down-regulation of BDNF mRNA in the hippocampus in response to restraint stress. The enhanced induction and prolonged expression of BDNF in response to chronic ECS and antidepressant drug treatments could promote neuronal survival, and protect neurons from the damaging effects of stress.

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Author and article information

Journal

Journal ID (nlm-ta): Nutrients

Journal ID (iso-abbrev): Nutrients

Journal ID (publisher-id): nutrients

Title: Nutrients

Publisher: MDPI

ISSN (Electronic): 2072-6643

Publication date (Electronic): 16 April 2019

Publication date Collection: April 2019

Volume: 11

Issue: 4

Electronic Location Identifier: 859

Affiliations

[1 ]MOE Key Laboratory of Protein Science, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China; chenhl16@ 123456mails.tsinghua.edu.cn (H.C.); qinghuangfgh@ 123456163.com (Q.H.); shunjia.zhang@ 123456yale.edu (S.Z.); hkq15@ 123456mails.tsinghua.edu.cn (K.H.); xiongwxiang@ 123456163.com (W.X.)

[2 ]School of Life Science and Technology, Tokyo Institute of Technology, Yokohama 2668501, Japan

[3 ]Environmental Health Science, School of Public Health, Yale University, New Haven, CT 06520, USA

[4 ]Research & Development Centre, Infinitus (China) Company Ltd., Guangzhou 510663, China; xiaolingyun12@ 123456126.com (L.X.); Renhuai.Cong@ 123456infinitus-int.com (R.C.)

Author notes

[* ]Correspondence: liuqf@ 123456tsinghua.edu.cn (Q.L.); zwang@ 123456tsinghua.edu.cn (Z.W.); Tel: +86-10-62772241 (Q.L. & Z.W.)

Article

Publisher ID: nutrients-11-00859

DOI: 10.3390/nu11040859

PMC ID: 6521158

PubMed ID: 30995790

SO-VID: c416d29a-9898-482f-8339-12e1143a2f8d

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

The Chinese Herbal Formula PAPZ Ameliorates Behavioral Abnormalities in Depressive Mice

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Abstract

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Chinese Journal of School Health

Most cited references 40

A neurotrophic model for stress-related mood disorders.

The tail suspension test as a model for assessing antidepressant activity: review of pharmacological and genetic studies in mice.

Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments.

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