Rapid and sustained restoration of astrocytic functions by ketamine in depression model mice

Ma, Xiaoyan; Yang, Shuo; Zhang, Zhaoxiang; Liu, Luping; Shi, Wenli; Yang, Sungchil; Li, Shupeng; Cai, Xiang; Zhou, Qiang

doi:10.1016/j.bbrc.2022.03.068

Cited by 11 publications

(6 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, this may need to be systematically tested for a few antidepressants of each class, as it was shown that fluoxetine treatment can reverse the chronic stress-induced GFAP reductions [ 124 ], but not citalopram [ 126 ]. Interestingly, recent work suggested that the fast-acting properties of some antidepressants may coincide with the reversal of chronic stress effects on the astroglial density or function [ 214 ] or rely on astroglia for their long-lasting effects [ 214 , 215 ]…”

Section: Targeting Astrocytes For Treatmentmentioning

confidence: 99%

“…Importantly, while riluzole, ceftriaxone, and harmine were shown to require chronic administration for antidepressant action, guanosine has rapid-acting antidepressant-like properties similar to ketamine and was shown to potentiate ketamine’s effects on GLT1 and GS activity [ 229 , 236 ]. Again, the requirement of GLT1/astroglia for the guanosine antidepressant action needs to be demonstrated, as the rapid-acting antidepressant effects of ketamine were shown to be independent of GLT1 [ 215 ]. Altogether, these findings support targeting GLT1 as a viable avenue for the treatment of MDD and PTSD, but the development of selective compounds is crucially needed [ 237 ].…”

Section: Targeting Astrocytes For Treatmentmentioning

confidence: 99%

See 1 more Smart Citation

Astroglial Dysfunctions in Mood Disorders and Rodent Stress Models: Consequences on Behavior and Potential as Treatment Target

Bansal,

Codeluppi,

Banasr

2024

IJMS

View full text Add to dashboard Cite

Astrocyte dysfunctions have been consistently observed in patients affected with depression and other psychiatric illnesses. Although over the years our understanding of these changes, their origin, and their consequences on behavior and neuronal function has deepened, many aspects of the role of astroglial dysfunction in major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) remain unknown. In this review, we summarize the known astroglial dysfunctions associated with MDD and PTSD, highlight the impact of chronic stress on specific astroglial functions, and how astroglial dysfunctions are implicated in the expression of depressive- and anxiety-like behaviors, focusing on behavioral consequences of astroglial manipulation on emotion-related and fear-learning behaviors. We also offer a glance at potential astroglial functions that can be targeted for potential antidepressant treatment.

show abstract

Section: Targeting Astrocytes For Treatmentmentioning

confidence: 99%

Section: Targeting Astrocytes For Treatmentmentioning

confidence: 99%

Astroglial Dysfunctions in Mood Disorders and Rodent Stress Models: Consequences on Behavior and Potential as Treatment Target

Bansal,

Codeluppi,

Banasr

2024

IJMS

View full text Add to dashboard Cite

show abstract

“…They showed that amitriptyline, one of tricyclic antidepressants, enhanced expression of BDNF in Cx43-knockdown astrocytes, and lysophosphatidic acid receptor (1/3) and activation of ERK signaling is involved in the enhanced BDNF expression by amitriptyline ( Tokunaga et al, 2022 ). Using the depression mouse models caused by chronic adreno-cortico-tropic-hormone (ACTH)- and chronic unpredictable mild stress (CUMS), fast-acting (1 h) antidepressant effects of ketamine has been reported ( Ma et al, 2022 ). The ketamine injection induced upregulation of glutamate transporter-1(GLT-1), glial fibrillary acidic protein (GFAP, a marker for astroglia), and BDNF, and reduced eukaryotic elongation factor 2 phosphorylation in the prelimbic prefrontal cortex in addition to reduced glutamate responses to synaptic stimulation in the cortical excitatory neurons.…”

Section: Bdnf-related Signaling and Depressionmentioning

confidence: 99%

“…The ketamine injection induced upregulation of glutamate transporter-1(GLT-1), glial fibrillary acidic protein (GFAP, a marker for astroglia), and BDNF, and reduced eukaryotic elongation factor 2 phosphorylation in the prelimbic prefrontal cortex in addition to reduced glutamate responses to synaptic stimulation in the cortical excitatory neurons. Interestingly, these changes by acute ketamine injection still occurred after GLT-1 knockdown, suggesting no involvement of GLT-1 upregulation and distinct contributions from astrocytes and neurons in the action of ketamine ( Ma et al, 2022 ). As expected, recent evidence demonstrates an important of glial dysfunction in the pathogenesis of emotional diseases including depression and of therapeutic strategies involving astrocytes via BDNF-dependent mechanisms ( Koizumi, 2021 ).…”

Section: Bdnf-related Signaling and Depressionmentioning

confidence: 99%

Involvement of brain-derived neurotrophic factor signaling in the pathogenesis of stress-related brain diseases

Numakawa,

Kajihara

2023

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Neurotrophins including brain-derived neurotrophic factor, BDNF, have critical roles in neuronal differentiation, cell survival, and synaptic function in the peripheral and central nervous system. It is well known that a variety of intracellular signaling stimulated by TrkB, a high-affinity receptor for BDNF, is involved in the physiological and pathological neuronal aspects via affecting cell viability, synaptic function, neurogenesis, and cognitive function. As expected, an alteration of the BDNF/TrkB system is suspected to be one of the molecular mechanisms underlying cognitive decline in cognitive diseases and mental disorders. Recent evidence has also highlighted a possible link between the alteration of TrkB signaling and chronic stress. Furthermore, it has been demonstrated that downregulation of the BDNF/TrkB system and chronic stress have a role in the pathogenesis of Alzheimer’s disease (AD) and mental disorders. In this review, we introduce current evidence showing a close relationship between the BDNF/TrkB system and the development of cognition impairment in stress-related disorders, and the possible contribution of the upregulation of the BDNF/TrkB system in a therapeutic approach against these brain diseases.

show abstract

“…Several studies show that AMPAR activation is necessary for the antidepressant actions of ketamine. In mouse models of depression, AMPAR inhibition had either diminished or fully eradicated the antidepressant effects of ketamine [ 131 , 132 , 133 , 134 ]. Furthermore, pre-treatment with AMPAR antagonists decreases levels of BDNF and the mechanistic target of rapamycin (mTOR) (a downstream effector of BDNF-TrkB signaling discussed below) in the prefrontal cortex and hippocampus.…”

Section: Reviewmentioning

confidence: 99%

Ketamine and the Disinhibition Hypothesis: Neurotrophic Factor-Mediated Treatment of Depression

Borsellino,

Krider,

Chea

et al. 2023

Pharmaceuticals

View full text Add to dashboard Cite

Ketamine is a promising alternative to traditional pharmacotherapies for major depressive disorder, treatment-resistant depression, and other psychiatric conditions that heavily contribute to the global disease burden. In contrast to the current standard of care medications for these disorders, ketamine offers rapid onset, enduring clinical efficacy, and unique therapeutic potential for use in acute, psychiatric emergencies. This narrative presents an alternative framework for understanding depression, as mounting evidence supports a neuronal atrophy and synaptic disconnection theory, rather than the prevailing monoamine depletion hypothesis. In this context, we describe ketamine, its enantiomers, and various metabolites in a range of mechanistic actions through multiple converging pathways, including N-methyl-D-aspartate receptor (NMDAR) inhibition and the enhancement of glutamatergic signaling. We describe the disinhibition hypothesis, which posits that ketamine’s pharmacological action ultimately results in excitatory cortical disinhibition, causing the release of neurotrophic factors, the most important of which is brain-derived neurotrophic factor (BDNF). BDNF-mediated signaling along with vascular endothelial growth factor (VEGF) and insulin-like growth factor 1 (IGF-1) subsequently give rise to the repair of neuro-structural abnormalities in patients with depressive disorders. Ketamine’s efficacious amelioration of treatment-resistant depression is revolutionizing psychiatric treatment and opening up fresh vistas for understanding the underlying causes of mental illness.

show abstract

Rapid and sustained restoration of astrocytic functions by ketamine in depression model mice

Cited by 11 publications

References 32 publications

Astroglial Dysfunctions in Mood Disorders and Rodent Stress Models: Consequences on Behavior and Potential as Treatment Target

Astroglial Dysfunctions in Mood Disorders and Rodent Stress Models: Consequences on Behavior and Potential as Treatment Target

Involvement of brain-derived neurotrophic factor signaling in the pathogenesis of stress-related brain diseases

Ketamine and the Disinhibition Hypothesis: Neurotrophic Factor-Mediated Treatment of Depression

Contact Info

Product

Resources

About