mPFC DCC coupling with CaMKII+ neuronal excitation participates in behavioral despair in male mice DOI Creative Commons

Ping Cheng,

Keke Ding,

Daokang Chen

et al.

Translational Psychiatry, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 14, 2025

A longed lack of control over harmful stimuli can lead to learned helplessness (LH), a significant factor in depression. However, the cellular and molecular mechanisms underlying LH, eventually behavioral despair, remain largely unknown. The deleted colorectal cancer (dcc) gene is associated with risk therapeutic potential regulation mechanism DCC despair are still uncertain. In this study, we showed that depressive stimulators, including lipopolysaccharide, unpredictable chronic mild stress, triggered an elevation expression medial prefrontal cortex (mPFC). Additionally, elevated mPFC was crucial inducing as evidenced by induction normal mice exacerbation LH upon overexpression. By contrast, neutralizing activity ameliorated LH-induced despair. Importantly, elucidated pathological attributable excessive excitation CaMKII+ neurons manner dependent on calpain-mediated degradation SCOP aberrant phosphorylation ERK signaling pathway. addition, increase led decreased excitability threshold mPFC, which supported observation ligand netrin 1 increased frequency action firing spontaneous excitatory postsynaptic currents neurons. conclusion, our data indicate triggers activation calpain-SCOP/ERK promote expression, represents target for treatment male mice.

Language: Английский

Current status of GABA receptor subtypes in analgesia DOI Open Access

Xunjia Qian,

Xinyi Zhao, Lulu Yu

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 168, P. 115800 - 115800

Published: Nov. 6, 2023

Gamma-aminobutyric acid (GABA), a non-protein-producing amino synthesized from the excitatory glutamate via enzyme glutamic decarboxylase, is extensively found in microorganisms, plants and vertebrates, abundantly expressed spinal cord brain. It major inhibitory neurotransmitter mammalian nervous system. GABA plays crucial roles regulation of synaptic transmission, promotion neuronal development relaxation, prevention insomnia depression. As neurotransmitter, pivotal pain sensation, which initiated by activation peripheral nociceptors transmitted to brain along nerves. exerts these directly acting on three types receptors: ionotropic GABAA GABAC receptors G protein-coupled GABAB receptor. The chloride-permeable ion channel mediate fast neurotransmission, while metabotropic receptor mediates slow effect. Different regulate sensation different signaling pathways. Here we highlight recent updates involvement specific their subtypes process sensation. Further understanding pathways will benefit novel analgesics for management targeting

Language: Английский

Citations

28
Repurposing General Anesthetic Drugs to Treat Depression: A New Frontier for Anesthesiologists in Neuropsychiatric Care DOI Creative Commons
Connor T. A. Brenna, Benjamin I. Goldstein, Carlos A. Zarate

et al.

Anesthesiology, Journal Year: 2024, Volume and Issue: 141(2), P. 222 - 237

Published: June 10, 2024

During the last 100 years, role of anesthesiologists in psychiatry has focused primarily on facilitating electroconvulsive therapy and mitigating postoperative delirium other perioperative neurocognitive disorders. The discovery rapid sustained antidepressant properties ketamine, early results suggesting that general anesthetic drugs (including nitrous oxide, propofol, isoflurane) have properties, positioned at a new frontier treatment neuropsychiatric Moreover, shared interest understanding biologic underpinnings as psychotropic agents is eroding traditional academic boundaries between anesthesiology psychiatry. This article presents brief overview novel antidepressants identifies promising future candidates for depression. authors issue call to action outline strategies foster collaborations psychiatrists they work toward common goals repurposing addressing mood disorders surgical patients.

Language: Английский

Citations

7
Effects of chronic stress on cognitive function – From neurobiology to intervention DOI Creative Commons
Milena Girotti, Sarah E. Bulin,

Flavia Carreño

et al.

Neurobiology of Stress, Journal Year: 2024, Volume and Issue: 33, P. 100670 - 100670

Published: Sept. 3, 2024

Exposure to chronic stress contributes considerably the development of cognitive impairments in psychiatric disorders such as depression, generalized anxiety disorder (GAD), obsessive-compulsive (OCD), post-traumatic (PTSD), and addictive behavior. Unfortunately, unlike mood-related symptoms, are not effectively treated by available therapies, a situation part resulting from still incomplete knowledge neurobiological substrates that underly domains difficulty generating interventions both efficacious safe. In this review, we will present an overview affected with specific focus on flexibility, behavioral inhibition, working memory. We then consider effects neuronal correlates function factors which may modulate interaction cognition. Finally, discuss intervention strategies for treatment stress-related gaps emerging new treatments under development. Understanding how impairment occurs during exposure is crucial make progress towards effective therapeutic approaches.

Language: Английский

Citations

7
Linalool, a Fragrance Compound in Plants, Protects Dopaminergic Neurons and Improves Motor Function and Skeletal Muscle Strength in Experimental Models of Parkinson’s Disease DOI Open Access

Wan‐Hsuan Chang,

Hung‐Te Hsu, Chih‐Cheng Lin

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2514 - 2514

Published: Feb. 21, 2024

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the gradual loss of dopaminergic neurons in substantia nigra pars compacta (SNpc), resulting reduced dopamine levels striatum and eventual onset motor symptoms. Linalool (3,7-dimethyl-1,6-octadien-3-ol) monoterpene aromatic plants exhibiting antioxidant, antidepressant, anti-anxiety properties. The objective this study to evaluate neuroprotective impacts linalool on SH-SY5Y cells, primary mesencephalic cortical treated with 1-methyl-4-phenylpyridinium ion (MPP

Language: Английский

Citations

6
Treatment of Depression in Huntington’s Disease: A Systematic Review DOI
Shayan Abdollah Zadegan, Frank Ramirez,

Kirthan S. Reddy

et al.

Journal of Neuropsychiatry, Journal Year: 2024, Volume and Issue: unknown

Published: March 26, 2024

Depression is a common psychiatric disorder among individuals with Huntington's disease (HD). in HD and major depressive appear to have different pathophysiological mechanisms. Despite the unique pathophysiology, treatment of depression based on data from general population. The objective this systematic review was conduct comprehensive evaluation available evidence. Preferred Reporting Items for Systematic Reviews Meta-Analyses guidelines were followed. Studies identified by searching MEDLINE, Embase, PsycInfo. initial search yielded 2,771 records, 41 which ultimately included. There 19 case reports, seven series, three cross-sectional studies, one qualitative study, nine nonrandomized two randomized trials included studies. most assessment tools Hospital Anxiety Scale (N=8), Beck Inventory (N=6), Hamilton Rating (N=6). Only 59% studies assessed symptoms scoring system. pharmacological options antidepressants antipsychotics. Nonpharmacological approaches multidisciplinary rehabilitation, psychotherapy, neurostimulation. Limited evidence available, literature consisted mainly reports series. This highlights knowledge gap pressing need HD-specific research determine efficacy HD.

Language: Английский

Citations

6
Fibre & fermented foods: differential effects on the microbiota-gut-brain axis DOI Creative Commons
Elizabeth M. Schneider, Ramya Balasubramanian,

Aimone Ferri

et al.

Proceedings of The Nutrition Society, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 16

Published: Oct. 25, 2024

The ability to manipulate brain function through the communication between microorganisms in gastrointestinal tract and along gut-brain axis has emerged as a potential option improve cognitive emotional health. Dietary composition patterns have demonstrated robust capacity modulate microbiota-gut-brain axis. With their possess pre-, pro-, post-, synbiotic properties, dietary fibre fermented foods stand out potent shapers of gut microbiota subsequent signalling brain. Despite this potential, few studies directly examined mechanisms that might explain beneficial action on axis, thus limiting insight treatments for dysfunction. Herein, we evaluate differential effects from whole food sources functioning. Potential mediating health via are described. Although more multimodal research combines psychological assessments biological sampling compare each type is needed, evidence accumulated date suggests fibre, foods, and/or combination within psychobiotic diet can be cost-effective convenient approach functioning across lifespan.

Language: Английский

Citations

6
Prenatal metal exposures and childhood gut microbial signatures are associated with depression score in late childhood DOI Creative Commons
Vishal Midya, Kiran Nagdeo, Jamil M. Lane

et al.

The Science of The Total Environment, Journal Year: 2024, Volume and Issue: 916, P. 170361 - 170361

Published: Jan. 24, 2024

Childhood depression is a major public health issue worldwide. Previous studies have linked both prenatal metal exposures and the gut microbiome to in children. However, few, if any, studied their interacting effect specific subgroups of

Language: Английский

Citations

5
Parvalbumin interneuron cell-to-network plasticity: mechanisms and therapeutic avenues DOI Creative Commons
Michael D. Hadler, Henrik Alle,

Jörg R. P. Geiger

et al.

Trends in Pharmacological Sciences, Journal Year: 2024, Volume and Issue: 45(7), P. 586 - 601

Published: May 18, 2024

Alzheimer's disease (AD) and schizophrenia (SCZ) represent two major neuropathological conditions with a high burden. Despite their distinct etiologies, patients suffering from AD or SCZ share common burden of disrupted memory functions unattended by current therapies. Recent preclinical analyses highlight cell-type-specific contributions parvalbumin interneurons (PVIs), particularly the plasticity cellular excitability, towards intact neuronal network function (cell-to-network plasticity) performance. Here we argue that deficits PVI cell-to-network may underlie in SCZ, explore therapeutic avenues: targeting PVI-specific neuromodulation, including neuropeptides, recruitment synchrony gamma frequency range (40 Hz) external stimulation. We finally propose these approaches be merged under consideration recent insights into human brain physiology.

Language: Английский

Citations

5
Depression clinical trials worldwide: a systematic analysis of the ICTRP and comparison with ClinicalTrials.gov DOI Creative Commons

Eugenia D. Namiot,

Diana Smirnovová,

Aleksandr V. Sokolov

et al.

Translational Psychiatry, Journal Year: 2024, Volume and Issue: 14(1)

Published: July 31, 2024

Abstract Major depressive disorder (MDD), commonly known as depression, affects over 300 million people worldwide of 2018 and presents a wide range clinical symptoms. The international trials registry platform (ICTRP) introduced by WHO includes aggregated data from ClinicalTrials.gov 17 other national registers, making it the largest trial platform. Here we analysed in ICTRP with aim providing comprehensive insights into on depression. Applying novel hidden duplicate identification method, 10,606 depression were identified ICTRP, ANZCTR being non- database at 1031 trials, followed IRCT 576 ISRCTN 501 CHiCTR 489 EUCTR 351 trials. top four most studied drugs, ketamine, sertraline, duloxetine, fluoxetine, consistent both groups, but had more for each drug compared to non-ClinicalTrials.gov group. Out 9229 interventional 663 unique agents identified, including approved drugs (74.5%), investigational (23.2%), withdrawn (1.8%), nutraceuticals (0.3%), illicit substances (0.2%). Both databases revealed that categories antidepressive (1172 659 non-ClinicalTrials.gov) nutrients, amino acids, chemical elements (250 non-ClinicalTrials.gov), indicating focus alternative treatments involving dietary supplements nutrients. Additionally, 26 targeting 16 different targets buprenorphine (opioid agonist), saredutant (NK2 antagonist), seltorexant (OX2 antagonist) frequently studied. This analysis addresses 40 treatment new classes like GABA modulators NMDA antagonists are offering prospects treating MDD, drug-resistant postpartum subtypes.

Language: Английский

Citations

5
The emergence of antidepressant drugs targeting GABAA receptors: A concise review DOI Creative Commons
Xénia Gonda, Frank I. Tarazi, Péter Döme

et al.

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 228, P. 116481 - 116481

Published: Aug. 13, 2024

Depression is among the most common psychiatric illnesses, which imposes a major socioeconomic burden on patients, caregivers, and public health system. Treatment with classical antidepressants (e.g. tricyclic selective serotonine reuptake inhibitors), primarily affect monoaminergic systems has several limitations, such as delayed onset of action moderate efficacy in relatively large proportion depressed patients. Furthermore, depression highly heterogeneus, its different subtypes, including post-partum depression, involve distinct neurobiology, warranting differential approach to pharmacotherapy. Given these shortcomings, need for novel that are superior faster fully justified. The development market introduction rapid-acting accelerated recent years. Some new act through GABAergic In this review, we discuss discovery, efficacy, limitations treatment classic antidepressants. We provide detailed discussion neurotransmission, special focus GABA

Language: Английский

Citations

5