Brain-spleen axis in health and diseases: A review and future perspective

Brain Research Bulletin, Год журнала: 2022, Номер 182, С. 130 - 140

Опубликована: Фев. 12, 2022

The spleen, an important tissue for the immune system, acts as a filter blood within system. Accumulating evidence suggests that spleen affects number of brain functions in health and diseases via modulation. Systemic inflammation or chronic social defeat stress (CSDS) can cause splenomegaly rodents. Interestingly, new antidepressant arketamine could normalize depression-like behaviors CSDS-susceptible mice. A recent study strongly supports direct connection pathway between whereby regulate humoral defense by two regions, such corticotropin-related neurons paraventricular nucleus (PVN) central amygdala (CeA). Furthermore, afferent efferent vagus nerve signaling may contribute to communication. In this article, we review findings brain-spleen axis diseases.

Язык: Английский

---

Arketamine, a new rapid-acting antidepressant: A historical review and future directions

Neuropharmacology, Год журнала: 2022, Номер 218, С. 109219 - 109219

Опубликована: Авг. 14, 2022

The N-methyl-d-aspartate receptor (NMDAR) antagonist (R,S)-ketamine causes rapid onset and sustained antidepressant actions in treatment-resistant patients with major depressive disorder (MDD) other psychiatric disorders, such as bipolar post-traumatic stress disorder. is a racemic mixture consisting of (R)-ketamine (or arketamine) (S)-ketamine esketamine), (S)-enantiomer having greater affinity for the NMDAR. In 2019, an esketamine nasal spray by Johnson & was approved USA Europe depression. contrast, increasing number preclinical studies show that arketamine has potency longer-lasting antidepressant-like effects than rodents, despite lower binding Importantly, side effects, i.e., psychotomimetic dissociative abuse liability, are less those animals humans. An open-label study demonstrated MDD. A phase 2 clinical trial MDD underway. This designed to review brief history novel arketamine, molecular mechanisms underlying its actions, future directions. article part Special Issue on 'Ketamine Metabolites'.

Язык: Английский

---

(R)-ketamine ameliorates demyelination and facilitates remyelination in cuprizone-treated mice: A role of gut–microbiota–brain axis

Neurobiology of Disease, Год журнала: 2022, Номер 165, С. 105635 - 105635

Опубликована: Янв. 24, 2022

Multiple sclerosis (MS) is the most common demyelinating disease that attacks central nervous system. We recently reported new antidepressant (R)-ketamine could ameliorate progression in experimental autoimmune encephalomyelitis model of MS. Cuprizone (CPZ) has been used to produce demyelination which resembles MS patients. This study was undertaken investigate whether affect CPZ-treated mice and remyelination after CPZ withdrawal. Repeated treatment with (10 mg/kg/day, twice weekly, for 6 weeks) significantly ameliorated activated microglia brain compared saline-treated mice. Furthermore, pretreatment ANA-12 (TrkB antagonist) blocked beneficial effects on The 16S rRNA analysis showed improved abnormal composition gut-microbiota decreased levels lactic acid In addition, there were significant correlations between (or microglial activation) relative abundance several microbiome, suggesting a link gut microbiota brain. Interestingly, facilitate conclusion, suggests through TrkB activation, gut-microbiota-microglia crosstalk may play role Therefore, it likely be therapeutic drug

Язык: Английский

---

(R)-ketamine as prophylactic and therapeutic drug for neurological disorders: Beyond depression

Neuroscience & Biobehavioral Reviews, Год журнала: 2022, Номер 139, С. 104762 - 104762

Опубликована: Июнь 30, 2022

Neurological disorders are the leading cause of disability and second death worldwide. The increasing social economic burdens neurological driven by global population growth aging. Depression is a common psychiatric symptom in numerous disorders. It also risk factor for Alzheimer's disease (AD) other dementias, Parkinson's (PD), stroke. rapid-acting sustained antidepressant actions (R,S)-ketamine severe depression was accidentally discovered. Interestingly, (R)-ketamine has greater potency longer-lasting antidepressant-like effects than (S)-ketamine rodents. Importantly, its side rodents humans lower those (S)-ketamine. Furthermore, could elicit beneficial various rodent models disorders, including PD, multiple sclerosis (MS), In this article, we review potential as prophylactic or therapeutic drug AD MS,

Язык: Английский

---

Targeting Sigma Receptors for the Treatment of Neurodegenerative and Neurodevelopmental Disorders

CNS Drugs, Год журнала: 2023, Номер 37(5), С. 399 - 440

Опубликована: Май 1, 2023

Язык: Английский

---

Ketamine and its two enantiomers in anesthesiology and psychiatry: A historical review and future directions

Journal of Anesthesia and Translational Medicine, Год журнала: 2024, Номер 3(3), С. 65 - 75

Опубликована: Июль 11, 2024

Ketamine, a dissociative anesthetic, is widely utilized in both human and veterinary anesthesia. Its (S)-enantiomer, esketamine, similarly employed for anesthesia analgesia. The anesthetic effects of ketamine esketamine arise from their antagonism the N-methyl-D-aspartate receptor (NMDAR). In field psychiatry, rapid-acting antidepressant properties severe depression have generated significant interest, resulting its increased off-label usage United States (U.S.). 2019, nasal spray received approval use U.S. Europe. However, concerns emerged regarding potential adverse effects, including long-term efficacy, addiction risks, suicide risk clinical settings. contrast, arketamine, (R)-enantiomer ketamine, exhibits superior longer-lasting rodent models depression, with fewer side compared to esketamine. Nevertheless, research on efficacy safety arketamine patients remains limited. This article provides concise exploration historical two enantiomers while also delving into future directions application these fields.

Язык: Английский

---

(R)-(-)-Ketamine: The Promise of a Novel Treatment for Psychiatric and Neurological Disorders

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(12), С. 6804 - 6804

Опубликована: Июнь 20, 2024

NMDA receptor antagonists have potential for therapeutics in neurological and psychiatric diseases, including neurodegenerative epilepsy, traumatic brain injury, substance abuse disorder (SUD), major depressive (MDD). (S)-ketamine was the first of a novel class antidepressants, rapid-acting to be approved medical use. The stereoisomer, (R)-ketamine (arketamine), is currently under development treatment-resistant depression (TRD). compound has demonstrated efficacy multiple animal models. Two clinical studies disclosed TRD bipolar depression. A study by drug sponsor recently failed reach priori endpoints but post hoc analysis revealed efficacy. value supported experimental data humans rodents, showing that it less sedating, does not produce marked psychotomimetic or dissociative effects, than (S)-ketamine, produces models range disorders. mechanisms action antidepressant effects are hypothesized due antagonism and/or non-NMDA mechanisms. We suggest further experimentation with will create improved medicines some disorders underserved current medications.

Язык: Английский

---

Key role of the gut–microbiota–brain axis via the subdiaphragmatic vagus nerve in demyelination of the cuprizone-treated mouse brain

Neurobiology of Disease, Год журнала: 2022, Номер 176, С. 105951 - 105951

Опубликована: Дек. 6, 2022

Multiple sclerosis (MS) is the most common demyelinating disease that attacks central nervous system. Dietary intake of cuprizone (CPZ) produces demyelination resembling patients with MS. Given role vagus nerve in gut-microbiota-brain axis development MS, we performed this study to investigate whether subdiaphragmatic vagotomy (SDV) affects CPZ-treated mice. SDV significantly ameliorated and microglial activation brain compared sham-operated Furthermore, 16S ribosomal RNA analysis revealed improved abnormal gut microbiota composition An untargeted metabolomic demonstrated blood levels metabolites mice Notably, there were correlations between or relative abundance several microbiome populations, suggesting a link brain. There also metabolites. Together, these data suggest CPZ through via nerve.

Язык: Английский

---

Exploring the multifaceted potential of (R)-ketamine beyond antidepressant applications

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Апрель 11, 2024

( R , S )- and )-ketamine have made significant progress in the treatment of treatment-resistant depression (TRD) become a research focus recent years. However, they both risks psychomimetic effects, dissociative abuse liability, which limit their clinical use. Recent preclinical studies shown that has more efficient lasting antidepressant effect with fewer side effects compared to )-ketamine. small-sample randomized controlled trial found although lower incidence adverse reactions adult TRD treatment, its efficacy is not superior placebo group, indicating advantage still needs further verification clarification. Moreover, an increasing body suggests might also applications prevention medical fields or diseases such as cognitive disorders, perioperative anesthesia, ischemic stroke, Parkinson’s disease, multiple sclerosis, osteoporosis, substance use inflammatory diseases, COVID-19, organophosphate poisoning. This article briefly reviews mechanism action on antidepressants related )-ketamine, fully revealing application potential development prospects, providing some references assistance for subsequent expanded research.

Язык: Английский

---

Effects of arketamine on depression-like behaviors and demyelination in mice exposed to chronic restrain stress: A role of transforming growth factor-β1

Journal of Affective Disorders, Год журнала: 2024, Номер 367, С. 745 - 755

Опубликована: Сен. 3, 2024

Chronic restrain stress (CRS) induces depression-like behaviors and demyelination in the brain; however, relationship between these remains unclear. Arketamine, (R)-enantiomer of ketamine, has shown rapid antidepressant-like effects CRS-exposed mice. We examined whether arketamine can improve both brains Additionally, we investigated role transforming growth factor β1 (TGF-β1) beneficial arketamine. A single dose (10 mg/kg) improved behavior corpus callosum Correlations were found this region. Furthermore, pretreatment with RepSox, an inhibitor TGF-β1 receptor, significantly blocked on Finally, a intranasal administration ameliorated The precise mechanisms by which contributes to remain These data suggest that CRS-induced may contribute behaviors, mitigate changes through TGF-β1-dependent mechanism.

Язык: Английский

---