Neuroinflammation, memory, and depression: new approaches to hippocampal neurogenesis

Journal of Neuroinflammation, Год журнала: 2023, Номер 20(1)

Опубликована: Ноя. 27, 2023

As one of most common and severe mental disorders, major depressive disorder (MDD) significantly increases the risks premature death other medical conditions for patients. Neuroinflammation is abnormal immune response in brain, its correlation with MDD receiving increasing attention. has been reported to be involved through distinct neurobiological mechanisms, among which dysregulation neurogenesis dentate gyrus (DG) hippocampus (HPC) The DG two niches adult mammalian neurotrophic factors are fundamental regulators this process. cell types mediating neuroinflammation include microglia, astrocytes, oligodendrocytes, meningeal leukocytes, peripheral cells selectively penetrate blood-brain barrier infiltrate into inflammatory regions. This review summarizes functions affected by during progression corresponding influences on memory patients model animals.

Язык: Английский

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NADPH-oxidases as potential pharmacological targets for thrombosis and depression comorbidity

Redox Biology, Год журнала: 2024, Номер 70, С. 103060 - 103060

Опубликована: Фев. 1, 2024

There is a complex interrelationship between the nervous system and cardiovascular system. Comorbidities of diseases (CVD) with mental disorders, vice versa, are prevalent. Adults disorders such as anxiety depression have higher risk developing CVD, people CVD an increased being diagnosed disorders. Oxidative stress one many pathways associated pathophysiology brain disease. Nicotinamide adenine dinucleotide phosphate oxidase (NOX) major generators reactive oxygen species (ROS) in mammalian cells, it enzyme that specifically produces superoxide. This review summarizes recent findings on consequences NOX activation thrombosis depression. It also discusses therapeutic effects pharmacological strategies inhibitors A better comprehension these processes could facilitate development new approaches for prevention treatment comorbidity

Язык: Английский

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Recognising depression in non-human primates: a narrative review of reported signs of depression

PeerJ, Год журнала: 2025, Номер 13, С. e18766 - e18766

Опубликована: Янв. 7, 2025

Major depressive disorder (depression) is a highly heterogenous human mental that may have equivalents in non-human animals. Research into depression teaches us about and can contribute to enhance welfare of Here, we narratively review how signs primates (NHPs) be observed based on symptoms the Diagnostic Statistical Manual Mental Disorders (DSM-5). Furthermore, propose diagnostic criteria NHP reports NHPs. We diagnose an with when it shows core sign (depressed mood or anhedonia) alongside at least three other DSM-5-derived depression. Results show four out six observable are present NHPs, occasionally lasting for months. However, only group NHPs one study met our proposed diagnosis call more research co-occurrence individual establish prevalence

Язык: Английский

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Effectiveness of positive allosteric modulators of metabotropic glutamate receptor 2/3 (mGluR2/3) in animal models of schizophrenia

Translational Psychiatry, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 14, 2025

Schizophrenia (SZ) is a deleterious brain disorder characterised by its heterogeneity and complex symptomatology consisting of positive, negative cognitive deficits. Current antipsychotic drugs ameliorate the positive symptomatology, but are inefficient in treating The neurodevelopmental glutamate hypothesis SZ has opened new avenues development targeting glutamatergic system. One these therapies involves allosteric modulators (PAMs) metabotropic receptors, mainly types 2/3 (mGluR2/3). mGluR2/3 PAMs selective for receptor, present high tolerability can modulate activity receptor long periods. There not much research clinical trials regarding PAMs. However, several lines evidence from animal models have indicated efficiency In this review, focusing on vivo studies, we will specifically discuss utilization various methods employed to assess behaviour before summarising obtained date field By doing so, aim deepen our understanding underlying mechanisms potential SZ. Overall, demonstrated attenuating SZ-like behavioural molecular deficits could be useful early management or treat specific subsets patients.

Язык: Английский

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Differential effects of chronic unpredictable stress on behavioral and molecular (cortisol and microglia-related neurotranscriptomic) responses in adult leopard (leo) zebrafish

Fish Physiology and Biochemistry, Год журнала: 2025, Номер 51(1)

Опубликована: Янв. 15, 2025

Язык: Английский

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Oxidative and Excitatory Neurotoxic Stresses in CRISPR/Cas9-Induced Kynurenine Aminotransferase Knockout Mice: A Novel Model for Despair-Based Depression and Post-Traumatic Stress Disorder

Frontiers in Bioscience-Landmark, Год журнала: 2025, Номер 30(1)

Опубликована: Янв. 20, 2025

Backgrounds: Memory and emotion are especially vulnerable to psychiatric disorders such as post-traumatic stress disorder (PTSD), which is linked disruptions in serotonin (5-HT) metabolism. Over 90% of the 5-HT precursor tryptophan (Trp) metabolized via Trp-kynurenine (KYN) metabolic pathway, generates a variety bioactive molecules. Dysregulation KYN metabolism, particularly low levels kynurenic acid (KYNA), appears be neuropsychiatric disorders. The majority KYNA produced by aadat (kat2) gene-encoded mitochondrial kynurenine aminotransferase (KAT) isotype 2. Little known about consequences deleting enzyme gene. Methods: In CRISPR/Cas9-induced knockout (kat2-/-) mice, we examined effects on emotion, memory, motor function, Trp its metabolite levels, activities plasma urine 8-week-old males compared wild-type mice. Results: Transgenic mice showed more depressive-like behaviors forced swim test, but not tail suspension, anxiety, or memory tests. They also had fewer center field corner entries, shorter walking distances, jumping counts open test. Plasma generally consistent with those urine: antioxidant KYNs, 5-hydroxyindoleacetic acid, indole-3-acetic were lower; KATs, kynureninase, monoamine oxidase/aldehyde dehydrogenase lower, 3-monooxygenase was higher; oxidative excitotoxicity indices higher. displayed depression-like behavior learned helplessness model, emotional indifference, deficits, coupled decrease KYNA, shift metabolism toward KYN-3-hydroxykynurenine partial gut microbial Trp-indole pathway metabolite. Conclusions: This first evidence that gene induces uniquely experiences despair, appear associated excitatory neurotoxic stresses. may lead development double-hit preclinical model despair-based depression, better understanding these complex conditions, effective therapeutic strategies elucidating relationship between PTSD pathogenesis.

Язык: Английский

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Efficacy, Tolerability, and Safety of Toludesvenlafaxine for the Treatment of Major Depressive Disorder—A Narrative Review

Pharmaceuticals, Год журнала: 2023, Номер 16(3), С. 411 - 411

Опубликована: Март 8, 2023

The estimated rate of treatment-resistant major depressive disorder (TRD) remains higher than 30%, even after the discovery multiple classes antidepressants in last 7 decades. Toludesvenlafaxine (ansofaxine, LY03005, or LPM570065) is a first-in-class triple monoaminergic reuptake inhibitor (TRI) that has reached clinical use. objective this narrative review was to summarize and preclinical evidence about efficacy, tolerability, safety toludesvenlafaxine. Based on results 17 reports retrieved literature, tolerability profiles toludesvenlafaxine were good all trials, pharmacokinetic parameters well described phase 1 trials. efficacy demonstrated one 2 3 trial, both primary secondary outcomes. In conclusion, highlights favorable only two short-term trials enrolled patients with (MDD) (efficacy for up eight weeks), indicating need more quality, larger-sample, longer-term Exploring new antidepressants, such as TRI, can be considered priority research due high rates TRD, but also significant percentages relapse MDD.

Язык: Английский

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Brain region–specific roles of brain-derived neurotrophic factor in social stress–induced depressive-like behavior

Neural Regeneration Research, Год журнала: 2024, Номер 20(1), С. 159 - 173

Опубликована: Апрель 3, 2024

Brain-derived neurotrophic factor is a key in stress adaptation and avoidance of social behavioral response. Recent studies have shown that brain-derived expression stressed mice brain region–specific, particularly involving the corticolimbic system, including ventral tegmental area, nucleus accumbens, prefrontal cortex, amygdala, hippocampus. Determining how participates processing different regions will deepen our understanding psychopathology. In this review, we discuss regulation stress-sensitive closely related to pathophysiology depression. We focused on associated molecular pathways neural circuits, with special attention factor–tropomyosin receptor kinase B signaling pathway area–nucleus accumbens dopamine circuit. determined stress-induced alterations levels are likely nature, severity, duration stress, especially above-mentioned system. Therefore, BDNF might be biological indicator regulating stress-related processes various regions.

Язык: Английский

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Insights for the Next Generation of Ketamine for the Treatment of Depressive Disorder

Journal of Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 5, 2025

Treatment-resistant depression responds quickly to ketamine. As an N-methyl-d-aspartate receptor (NMDAR) antagonist, ketamine may affect prefrontal cortex (PFC) neurons. Recent investigations reveal that the (R)-enantiomer is most effective and least abuseable antidepressant. The Food Drug Administration approves only (S)-enantiomer for medical usage. (2R,6R)-Hydroxynorketamine (HNK) inhibits mGlu2, linked a Gi, in presynaptic glutamatergic neurons, increasing brain-derived neurotrophic factor (BDNF) release, which autocrinely activates Tropomyosin kinase B (TrkB) promotes synaptogenesis. Ketamine, originally anesthetic, has garnered attention its many pharmacological effects, including potential as rapid-acting antidepressant recreational use. In this Perspective, we explore synthesis, pharmacology, metabolism, effects of metabolites animal human studies explain difference biological activity between enantiomers.

Язык: Английский

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Unveiling the Mechanisms of a Remission in Major Depressive Disorder (MDD)-like Syndrome: The Role of Hippocampal Palmitoyltransferase Expression and Stress Susceptibility

Biomolecules, Год журнала: 2025, Номер 15(1), С. 67 - 67

Опубликована: Янв. 5, 2025

Post-translational modifications of proteins via palmitoylation, a thioester linkage 16-carbon fatty acid to cysteine residue, reversibly increases their affinity for cholesterol-rich lipid rafts in membranes, changing function. Little is known about how altered palmitoylation affects function at the systemic level and contributes CNS pathology. However, recent studies suggested role downregulation palmitoyl acetyltransferase (DHHC) 21 gene expression development Major Depressive Disorder (MDD)-like syndrome. Here, we sought investigate susceptibility (sucrose preference below 65%) or resilience > stress-induced anhedonia DHHC hippocampus C57BL/6J mice during phase spontaneous recovery from anhedonia. Because MDD recurrent disorder, it important understand molecular mechanisms underlying not only symptomatic disease but also state temporary remission. Indeed, changes associated with application pharmacotherapy remission stage are currently well understood. Therefore, used mouse model chronic stress address these questions. The protocol consisted rat exposure, social defeat, restraint stress, tail suspension. Mice group were treated, received imipramine drinking water (7 mg/kg/day), intraperitoneal injections dicholine succinate (DS; 25 mg/kg/day) starting 7 days prior continuing 14-day procedure. Controls either untreated treated two drugs. At 1st after-stress week, sucrose preference, forced swim, novel cage, fear-conditioning tests carried out; test 5-day Morris maze followed by sacrifice on post-stress day 31 all performed. Transcriptome Illumina analysis hippocampi was out. Using RT-PCR, hippocampal Dhhc3, Dhhc7, Dhhc8, Dhhc13, Dhhc14, Dhhc21 studied. We found that lowered subgroup exhibited prolonged floating behavior, behavioral invigoration, impaired contextual fear conditioning, while auditory conditioning unaltered. phase, no found, acquisition unchanged groups. In anhedonic, resilient animals, Dhhc8 lowered, Dhhc14 increased. Antidepressant treatment drug partially preserved abnormalities. Our data suggest likely be implicated depression stage, serving as targets preventive therapy.

Язык: Английский

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