Dysfunction of Glutamatergic Synaptic Transmission in Depression: Focus on AMPA Receptor Trafficking

He, Jin-Gang; Zhou, Hai-Yun; Wang, Fang; Chen, Jianguo

doi:10.1016/j.bpsgos.2022.02.007

Cited by 14 publications

(4 citation statements)

References 119 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NFAT can activate the transcription of a variety of genes, including apoptotic genes, genes involved in neuronal and glial development, and as the name indicates, genes involved in immune responses and inflammation [ 42 , 68 ]. Due to the major role of changes in glutamate signaling and AMPA receptor activity in depression [ 69 , 70 ] and the rise in GluR1 in mice overexpressing calcineurin, we hypothesize that the effects of chlorogenic acid may be mediated by changes in neuronal transmission. However, effects on pathways regulated by calcineurin’s transcriptional activity could also play a role in the protective function of chlorogenic acid and CAW, and future studies are needed to address these downstream effects.…”

Section: Discussionmentioning

confidence: 99%

Chlorogenic Acids, Acting via Calcineurin, Are the Main Compounds in Centella asiatica Extracts That Mediate Resilience to Chronic Stress in Drosophila melanogaster

Holvoet,

Long,

Yang

et al. 2023

Nutrients

View full text Add to dashboard Cite

Common symptoms of depressive disorders include anhedonia, sleep problems, and reduced physical activity. Drugs used to treat depression mostly aim to increase serotonin signaling but these can have unwanted side effects. Depression has also been treated by traditional medicine using plants like Centella asiatica (CA) and this has been found to be well tolerated. However, very few controlled studies have addressed CA’s protective role in depression, nor have the active compounds or mechanisms that mediate this function been identified. To address this issue, we used Drosophila melanogaster to investigate whether CA can improve depression-associated symptoms like anhedonia and decreased climbing activity. We found that a water extract of CA provides resilience to stress induced phenotypes and that this effect is primarily due to mono-caffeoylquinic acids found in CA. Furthermore, we describe that the protective function of CA is due to a synergy between chlorogenic acid and one of its isomers also present in CA. However, increasing the concentration of chlorogenic acid can overcome the requirement for the second isomer. Lastly, we found that chlorogenic acid acts via calcineurin, a multifunctional phosphatase that can regulate synaptic transmission and plasticity and is also involved in neuronal maintenance.

show abstract

Section: Discussionmentioning

confidence: 99%

Chlorogenic Acids, Acting via Calcineurin, Are the Main Compounds in Centella asiatica Extracts That Mediate Resilience to Chronic Stress in Drosophila melanogaster

Holvoet,

Long,

Yang

et al. 2023

Nutrients

View full text Add to dashboard Cite

show abstract

“…Dysfunction of glutamatergic neurotransmission is well established in depression [ 33 ]. Targeting the regulation of glutamate and glutamatergic-related pathways may contribute to the development of novel antidepressants (such as esketamine, approved by the FDA for the treatment of treatment-resistant depression) [ 34 , 35 , 36 ].…”

Section: The Function Of the Prion Protein (Prp C ...mentioning

confidence: 99%

New Light on Prions: Putative Role of PrPc in Pathophysiology of Mood Disorders

Chrobak,

Pańczyszyn-Trzewik,

Król

et al. 2024

IJMS

View full text Add to dashboard Cite

Mood disorders are highly prevalent and heterogenous mental illnesses with devastating rates of mortality and treatment resistance. The molecular basis of those conditions involves complex interplay between genetic and environmental factors. Currently, there are no objective procedures for diagnosis, prognosis and personalization of patients’ treatment. There is an urgent need to search for novel molecular targets for biomarkers in mood disorders. Cellular prion protein (PrPc) is infamous for its potential to convert its insoluble form, leading to neurodegeneration in Creutzfeldt-Jacob disease. Meanwhile, in its physiological state, PrPc presents neuroprotective features and regulates neurotransmission and synaptic plasticity. The aim of this study is to integrate the available knowledge about molecular mechanisms underlying the impact of PrPc on the pathophysiology of mood disorders. Our review indicates an important role of this protein in regulation of cognitive functions, emotions, sleep and biological rhythms, and its deficiency results in depressive-like behavior and cognitive impairment. PrPc plays a neuroprotective role against excitotoxicity, oxidative stress and inflammation, the main pathophysiological events in the course of mood disorders. Research indicates that PrPc may be a promising biomarker of cognitive decline. There is an urgent need of human studies to elucidate its potential utility in clinical practice.

show abstract

“…Pharmacological evidence suggests that abnormal glutamatergic and serotonergic neurotransmission may be associated with the pathophysiology of depression (He et al 2023). Here, we observed that the diabetic animals had signi cantly lower levels of glutamate receptors like NMDAR1 (50.61% ± 9.19), NMDAR2 (88.3% ± 6.2), Glu2R (31.33% ± 7.3) and reduced levels the 5-HTT (37% ± 9.9) than the control group.…”

Section: Diabetic Animals Show Dysregulation Of Neurotransmitter Rece...mentioning

confidence: 99%

Semaglutide Attenuates Anxious And Depressive-Like Behaviors and Reverses The Cognitive Impairment in a Type 2 Diabetes Mellitus Via The Microbiota-Gut-Brain Axis

de Paiva,

Silva,

Mendonça

et al. 2023

Preprint

View full text Add to dashboard Cite

Newly conducted research suggests that metabolic disorders, like diabetes and obesity, play a significant role as risk factors for psychiatric disorders. This connection presents a potential avenue for creating novel antidepressant medications by repurposing drugs originally developed to address antidiabetic conditions. Earlier investigations have shown that GLP-1 analogs exhibit neuroprotective qualities in various models of neurological diseases, encompassing conditions such as Alzheimer's disease, Parkinson's disease, and stroke. Moreover, GLP-1 analogs have demonstrated the capability to enhance neurogenesis, a process recognized for its significance in memory formation and the cognitive and emotional aspects of information processing. Nonetheless, whether semaglutide holds efficacy as both an antidepressant and anxiolytic agent remains uncertain. To address this, our study focused on a mouse model of depression linked to type 2 diabetes induced by a High Fat Diet (HFD). In this model, we administered semaglutide (0.05mg/Kg intraperitoneally) on a weekly basis to evaluate its potential as a therapeutic option for depression and anxiety. Diabetic mice had higher blood glucose, lipidic profile, and insulin resistance. Moreover, mice fed HFD showed higher serum IL-1β and LPS associated with impaired humor and cognition. The analysis of behavioral responses revealed that the administration of Semaglutide effectively mitigated depressive- and anxiety-like behaviors, concurrently demonstrating an enhancement in cognitive function. Additionally, Semaglutide treatment protected synaptic plasticity and reversed the hippocampal neuroinflammation induced by HFD fed, improving activation of the insulin pathway, demonstrating the protective effects of Semaglutide. We also found that Semaglutide treatment decreased astrogliosis and microgliosis in the dentate gyrus region of the hippocampus. In addition, Semaglutide prevented the DM2-induced impairments of POMC, and GPR43 and simultaneously increased the NeuN + and GLP-1R + neurons in the hippocampus. Our data also showed that Semaglutide increased the 5-HT and its receptor (5-HTT) and glutamatergic receptors in the hippocampus. At last, Semaglutide changed the gut microbiota profile (increasing Bacterioidetes, Bacteroides acidifaciens, and Blautia coccoides) and decreased leaky gut, improving the gut-brain axis. Taken together, Semaglutide has the potential to act as a therapeutic tool for depression and anxiety.

show abstract

Dysfunction of Glutamatergic Synaptic Transmission in Depression: Focus on AMPA Receptor Trafficking

Cited by 14 publications

References 119 publications

Chlorogenic Acids, Acting via Calcineurin, Are the Main Compounds in Centella asiatica Extracts That Mediate Resilience to Chronic Stress in Drosophila melanogaster

Chlorogenic Acids, Acting via Calcineurin, Are the Main Compounds in Centella asiatica Extracts That Mediate Resilience to Chronic Stress in Drosophila melanogaster

New Light on Prions: Putative Role of PrPc in Pathophysiology of Mood Disorders

Semaglutide Attenuates Anxious And Depressive-Like Behaviors and Reverses The Cognitive Impairment in a Type 2 Diabetes Mellitus Via The Microbiota-Gut-Brain Axis

Contact Info

Product

Resources

About