Rapid and long-lasting antidepressant-like effects of ketamine and their relationship with the expression of brain enzymes, BDNF, and astrocytes

Viana, Glauce Socorro de Barros; Vale, Eduardo Mulato do; Araújo, Agf; Coelho, Nhv; Andrade, Stephanie; Costa, Rafael; Aquino, Pedro Everson Alexandre de; Sousa, Caren Nádia Soares de; Medeiros, Ingridy S.; Vasconcelos, Silvânia Maria Mendes; Neves, Kelly Rose Tavares

doi:10.1590/1414-431x202010107

Cited by 12 publications

(8 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Stress-induced decreases in levels of BDNF in the mouse hippocampus and the ventromedial prefrontal cortex is effectively restored with ketamine administration ( 102 – 105 ). Ketamine also acutely increases BDNF levels in the hippocampus and amygdala ( 106 – 111 ), dentate gyrus ( 109 ), and serum ( 112 ) of rodents. Administration of a TrkB inhibitor to the hippocampus blocks ketamine’s behavioral and molecular effects in a rat model of depression ( 81 , 113 ).…”

Section: Resultsmentioning

confidence: 99%

“…Significantly increased levels of BDNF promotor IV’s transcriptional activity has also been found post-ketamine ( 118 ). Ketamine decreases levels of a transcriptional regulator, histone deacetylase (HDAC), in the mouse striata, hippocampus, and PFC ( 109 ). However, knocking out histone deacetylase 5 (HDAC5) resulted in a dysregulated increase of BDNF, which abolished ketamine-induced increases ( 118 ).…”

Section: Resultsmentioning

confidence: 99%

“…Constitutively active GSK-3 is associated with resistance to ketamine’s antidepressant effect, and the usage of a GSK-3 inhibitor, lithium, mimics ketamine’s effects ( 149 ). Ketamine has shown to decrease levels of GSK-3 in the mouse hippocampus, striata, dentate gyrus, and PFC ( 109 ), and may also act through increasing levels of phosphorylated GSK-3β, the inactive form, in rat prefrontal cortex ( 151 , 152 ). GSK-3 inhibitors act to augment antidepressant-like effects of ketamine when the dose of ketamine is at a sub-threshold value ( 152 ).…”

Section: Resultsmentioning

confidence: 99%

“…BDNF upregulation after ketamine administration may partially explain ketamine’s mechanism in BD ( 191 ). Patients with euthymic BD have reported decreased expression of HDAC genes compared to control ( 192 ), and ketamine has shown to alter levels of HDAC in animal models as well ( 109 , 193 ), suggesting the involvement of epigenetic mechanisms of ketamine.…”

Section: Resultsmentioning

confidence: 99%

See 3 more Smart Citations

The Mechanisms Behind Rapid Antidepressant Effects of Ketamine: A Systematic Review With a Focus on Molecular Neuroplasticity

2022

View full text Add to dashboard Cite

The mechanism of action underlying ketamine’s rapid antidepressant effects in patients with depression, both suffering from major depressive disorder (MDD) and bipolar disorder (BD), including treatment resistant depression (TRD), remains unclear. Of the many speculated routes that ketamine may act through, restoring deficits in neuroplasticity may be the most parsimonious mechanism in both human patients and preclinical models of depression. Here, we conducted a literature search using PubMed for any reports of ketamine inducing neuroplasticity relevant to depression, to identify cellular and molecular events, relevant to neuroplasticity, immediately observed with rapid mood improvements in humans or antidepressant-like effects in animals. After screening reports using our inclusion/exclusion criteria, 139 publications with data from cell cultures, animal models, and patients with BD or MDD were included (registered on PROSPERO, ID: CRD42019123346). We found accumulating evidence to support that ketamine induces an increase in molecules involved in modulating neuroplasticity, and that these changes are paired with rapid antidepressant effects. Molecules or complexes of high interest include glutamate, AMPA receptors (AMPAR), mTOR, BDNF/TrkB, VGF, eEF2K, p70S6K, GSK-3, IGF2, Erk, and microRNAs. In summary, these studies suggest a robust relationship between improvements in mood, and ketamine-induced increases in molecular neuroplasticity, particularly regarding intracellular signaling molecules.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

The Mechanisms Behind Rapid Antidepressant Effects of Ketamine: A Systematic Review With a Focus on Molecular Neuroplasticity

2022

View full text Add to dashboard Cite

show abstract

“…3a, b ). Moreover, the increase of mTORC1 activation caused by the rapid-antidepressant Ketamine promotes the expression of BDNF [ 26 , 27 ]. To mimic the effect of mTORC1 activity changes in depression in vivo, HT-22 and BV2 were treated with mTORC1 inhibitor rapamycin (200 nM), and then the changes of Pdcd4 and BDNF expression were measured by western blot and ELISA.…”

Section: Resultsmentioning

confidence: 99%

The brain targeted delivery of programmed cell death 4 specific siRNA protects mice from CRS-induced depressive behavior

et al. 2021

View full text Add to dashboard Cite

Depression is one of the most common psychiatric disorders. Recently, studies demonstrate that antidepressants generating BDNF not only maintain synaptic signal transmission but also repress neuroinflammatory cytokines such as IL-6 and IL-1β. Therefore, promoting BDNF expression provides a strategy for the treatment of depression. Our recent research has indicated that programmed cell death 4 (Pdcd4) is a new target for antidepressant treatment by facilitating BDNF. Herein, we modified Pdcd4 specific small interfering RNA (siPdcd4) with the rabies virus glycoprotein peptide (RVG/siPdcd4) which enables it cross the blood-brain barrier (BBB). We found that RVG/siPdcd4 complex was selectively delivered to neurons and microglia and silenced the expression of Pdcd4, thereby up-regulating the level of BDNF and down-regulating IL-6 and IL-1β expression. More importantly, RVG/siPdcd4 injection attenuated synaptic plasticity impairment and protected mice from CRS-induced depressive behavior. These findings suggest that RVG/siPdcd4 complex is a potential therapeutic medicine for depression.

show abstract

Baicalin Ameliorates Corticosterone-Induced Depression by Promoting Neurodevelopment of Hippocampal via mTOR/GSK3β Pathway

Wang

Cheng

Lu³

et al. 2023

Chin. J. Integr. Med.

View full text Add to dashboard Cite

Rapid and long-lasting antidepressant-like effects of ketamine and their relationship with the expression of brain enzymes, BDNF, and astrocytes

Cited by 12 publications

References 41 publications

The Mechanisms Behind Rapid Antidepressant Effects of Ketamine: A Systematic Review With a Focus on Molecular Neuroplasticity

The Mechanisms Behind Rapid Antidepressant Effects of Ketamine: A Systematic Review With a Focus on Molecular Neuroplasticity

The brain targeted delivery of programmed cell death 4 specific siRNA protects mice from CRS-induced depressive behavior

Baicalin Ameliorates Corticosterone-Induced Depression by Promoting Neurodevelopment of Hippocampal via mTOR/GSK3β Pathway

Contact Info

Product

Resources

About