Publication

Involvement of the agmatinergic system in the depressive-like phenotype of the Crtc1 knockout mouse model of depression

Abstract

Recent studies implicate the arginine-decarboxylation product agmatine in mood regulation. Agmatine has antidepressant properties in rodent models of depression, and agmatinase (Agmat), the agmatine-degrading enzyme, is upregulated in the brains of mood disorder patients. We have previously shown that mice lacking CREB-regulated transcription coactivator 1 (CRTC1) associate behavioral and molecular depressive-like endophenotypes, as well as blunted responses to classical antidepressants. Here, the molecular basis of the behavioral phenotype of Crtc1(-/-) mice was further examined using microarray gene expression profiling that revealed an upregulation of Agmat in the cortex of Crtc1(-/-) mice. Quantitative polymerase chain reaction and western blot analyses confirmed Agmat upregulation in the Crtc1(-/-) prefrontal cortex (PFC) and hippocampus, which were further demonstrated by confocal immunofluorescence microscopy to comprise an increased number of Agmat-expressing cells, notably parvalbumin-and somatostatin-positive interneurons. Acute agmatine and ketamine treatments comparably improved the depressive-like behavior of male and female Crtc1(-/-) mice in the forced swim test, suggesting that exogenous agmatine has a rapid antidepressant effect through the compensation of agmatine deficit because of upregulated Agmat. Agmatine rapidly increased brain-derived neurotrophic factor (BDNF) levels only in the PFC of wild-type (WT) females, and decreased eukaryotic elongation factor 2 (eEF2) phosphorylation in the PFC of male and female WT mice, indicating that agmatine might be a fast-acting antidepressant with N-methyl-D-aspartate (NMDA) receptor antagonist properties. Collectively, these findings implicate Agmat in the depressive-like phenotype of Crtc1(-/-) mice, refine current understanding of the agmatinergic system in the brain and highlight its putative role in major depression.

About this result
This page is automatically generated and may contain information that is not correct, complete, up-to-date, or relevant to your search query. The same applies to every other page on this website. Please make sure to verify the information with EPFL's official sources.
Related concepts (46)
Antidepressant
Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include dry mouth, weight gain, dizziness, headaches, sexual dysfunction, and emotional blunting. There is an increased risk of suicidal thinking and behavior when taken by children, adolescents, and young adults. Discontinuation syndrome, which resembles recurrent depression in the case of the SSRI class, may occur after stopping the intake of any antidepressant, the effects of which may be permanent and irreversible.
Depression (mood)
Depression is a mental state of low mood and aversion to activity. It affects more than 280 million people of all ages (about 3.5% of the global population). Depression affects a person's thoughts, behavior, feelings, and sense of well-being. Depressed people often experience loss of motivation or interest in, or reduced pleasure or joy from, experiences that would normally bring them pleasure or joy.
Management of depression
Management of depression is the treatment of depression that may involve a number of different therapies: medications, behavior therapy, psychotherapy, and medical devices. Depression is a symptom of some physical diseases; a side effect of some drugs and medical treatments; and a symptom of some mood disorders such as major depressive disorder or dysthymia. Physical causes are ruled out with a clinical assessment of depression that measures vitamins, minerals, electrolytes, and hormones.
Show more
Related publications (43)

Linking connectivity of deep brain stimulation of nucleus accumbens area with clinical depression improvements: a retrospective longitudinal case series

Dimitri Nestor Alice Van De Ville, Maria Giulia Preti, Thuy Anh Khoa Nguyen, Katrin Petermann, Simona Leserri

Treatment-resistant depression is a severe form of major depressive disorder and deep brain stimulation is currently an investigational treatment. The stimulation's therapeutic effect may be explained through the functional and structural connectivities be ...
SPRINGER HEIDELBERG2023

Dynamic functional hippocampal markers of residual depressive symptoms in euthymic bipolar disorder

Dimitri Nestor Alice Van De Ville, Julian Gaviria

Objectives: Bipolar disorder (BD) is a severe, chronic, affective disorder characterized by recurrent switching between mood states, psychomotor and cognitive symptoms, which can linger in euthymic states as residual symptoms. Hippocampal alterations may p ...
WILEY2023

Widespread intra-axonal signal fraction abnormalities in bipolar disorder from multicompartment diffusion MRI: Sensitivity to diagnosis, association with clinical features and pharmacologic treatment

Erick Jorge Canales Rodriguez

Despite diffusion tensor imaging (DTI) evidence for widespread fractional anisotropy (FA) reductions in the brain white matter of patients with bipolar disorder, questions remain regarding the specificity and sensitivity of FA abnormalities as opposed to o ...
WILEY2023
Show more
Related MOOCs (12)
Simulation Neurocience
Learn how to digitally reconstruct a single neuron to better study the biological mechanisms of brain function, behaviour and disease.
Simulation Neurocience
Learn how to digitally reconstruct a single neuron to better study the biological mechanisms of brain function, behaviour and disease.
Simulation Neurocience
Learn how to digitally reconstruct a single neuron to better study the biological mechanisms of brain function, behaviour and disease.
Show more

Graph Chatbot

Chat with Graph Search

Ask any question about EPFL courses, lectures, exercises, research, news, etc. or try the example questions below.

DISCLAIMER: The Graph Chatbot is not programmed to provide explicit or categorical answers to your questions. Rather, it transforms your questions into API requests that are distributed across the various IT services officially administered by EPFL. Its purpose is solely to collect and recommend relevant references to content that you can explore to help you answer your questions.