Novel rapid-acting glutamatergic modulators: Targeting the synaptic plasticity in depression

Wang, Yating; Wang, Xiaole; Feng, Sitong; Chen, Nai‐Hong; Wang, Zhenzhen; Zhang, Yi

doi:10.1016/j.phrs.2021.105761

Cited by 44 publications

(23 citation statements)

References 237 publications

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“…Again, we observed a clear contrast between the enrichments in the brain and non-brain tissue (Supplementary Figure S14). Consistent with our FUMA-based results and prior reports 12,14 , the strongest associations were measured for neuronal cell types, phenotypically manifested by severe synaptic loss and deficits in functional connectivity 64,65 . Conversely, to our knowledge, the reported association of MD with astrocytes and oligodendrocyte lineages have not yet been described by genetic data, albeit having support in behavioral and postmortem studies 66-68 .…”

Section: Resultssupporting

confidence: 92%

Identification of 64 new risk loci for major depression, refinement of the genetic architecture and risk prediction of recurrence and comorbidities

Als

Kurki

Grove

et al. 2022

Preprint

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Major depression (MD) is a common mental disorder and a leading cause of disability worldwide. We conducted a GWAS meta-analysis of more than 1.3 million individuals, including 371,184 with MD, identifying 243 risk loci. Sixty-four loci are novel, including glutamate and GABA receptors that are targets for antidepressant drugs. Several biological pathways and components were enriched for genetic MD risk, implicating neuronal development and function. Intersection with functional genomics data prioritized likely causal genes and revealed novel enrichment of prenatal GABAergic neurons, astrocytes and oligodendrocyte lineages. We found MD to be highly polygenic, with around 11,700 variants explaining 90% of the SNP heritability. Bivariate Gaussian mixture modeling estimated that > 97% of risk variants for other psychiatric disorders (anxiety, schizophrenia, bipolar disorder and ADHD) are influencing MD risk when both concordant and discordant variants are considered, and nearly all MD risk variants influence educational attainment. Additionally, we demonstrated that MD genetic risk is associated with impaired complex cognition, including verbal reasoning, attention, abstraction and mental flexibility. Analyzing Danish nation-wide longitudinal data, we dissected the genetic and clinical heterogeneity, revealing distinct polygenic architectures across case subgroups of MD recurrency and psychiatric comorbidity and demonstrating two- to six-fold increases in absolute risks for developing comorbid psychiatric disorders among MD cases with the highest versus the lowest polygenic burden. The results deepen the understanding of the biology underlying MD and its progression and inform precision medicine approaches in MD.

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Section: Resultssupporting

confidence: 92%

Identification of 64 new risk loci for major depression, refinement of the genetic architecture and risk prediction of recurrence and comorbidities

Als

Kurki

Grove

et al. 2022

Preprint

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“…Furthermore, clinical studies using brain imaging have shown almost always a significant reduction in the volume of specific brain areas such as cerebral cortex and hippocampus of depressed patients [50,51]. Many evidences suggest that chronic administration of antidepressant drugs is able to prevent, reduce or abolish the loss of neuronal trophism and dendritic spine deficiency in rats subjected to chronic stress [52] as well as the loss of cortical and/or hippocampal volume in depressed patient that follow carefully an appropriate therapy [53]. These experimental and clinical evidences allowed a great revolution in understanding both the neurobiological basis of mood disorders and the underlying molecular mechanisms of the therapeutic action of antidepressant drugs.…”

Section: Melatonin and Mood Disordersmentioning

confidence: 99%

Melatonin: From Neurobiology to Treatment

Biggio

Talani

et al. 2021

Brain Sciences

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Melatonin, the major regulator of the sleep/wake cycle, also plays important physiological and pharmacological roles in the control of neuronal plasticity and neuroprotection. Accordingly, the secretion of this hormone reaches the maximal extent during brain development (childhood-adolescence) while it is greatly reduced during aging, a condition associated to altered sleep pattern and reduced neuronal plasticity. Altogether, these properties of melatonin have allowed us to demonstrate in both experimental models and clinical studies the great chronobiotic efficacy and sleep promoting effects of exogenous melatonin. Thus, the prolonged release formulation of melatonin, present as a drug in the pharmaceutical market, has been recently recommended for the treatment of insomnia in over 55 years old subjects.

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“…It is well known that the pathogenesis of mental disorders could be explained by a variety of hypotheses, such as the neuroinflammation hypothesis (Dey and Hankey Giblin, 2018;Li et al, 2022), the cyclic adenosine monophosphate response element binding protein (CREB)-brain-derived neurotrophic factor (BDNF) signaling impairment hypothesis (Koch et al, 2009;Tan et al, 2022), and the neurotransmission dysfunction hypothesis (Wang et al, 2021;Yan and Rein, 2022). The neuroprotective effect of LPS preconditioning in cerebral ischemia and traumatic brain injury has been reported to be associated with its preventive effect on the pathological progression of neuroinflammation through mechanisms such as nuclear factor-κB (NF-κB) inhibition and interferon regulatory factor (IRF) activation (Stevens et al, 2011;Vartanian et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic and Prophylactic Effects of Amphotericin B Liposomes on Chronic Social Defeat Stress-Induced Behavioral Abnormalities in Mice

Huang

et al. 2022

Front. Pharmacol.

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Recently, innate immune system stimulants, such as lipopolysaccharide (LPS) and macrophage-colony stimulating factor (M-CSF), were reported to prevent and reverse chronic stress-induced behavioral abnormalities, suggesting that innate immune stimulation could be a potential strategy for the treatment and prevention of mental disorders. Amphotericin B liposome is a clinically available antifungal medication that can stimulate macrophages and microglia. We hypothesize that amphotericin B liposome may be used to prevent and reverse behavioral abnormalities triggered by chronic stress. As expected, our results showed that a single injection of amphotericin B liposome (1 mg/kg) immediately after stress cessation reversed the decrease in time spent in the interaction zone in the social interaction test (SIT) and the increase in immobility time in the tail suspension test (TST) and forced swimming test (FST) in mice caused by chronic social defeat stress (CSDS). In addition, a single injection of amphotericin B liposomes (1 mg/kg) 1 day before stress exposure was found to prevent the CSDS-induced decrease in time spent in the interaction zone in the SIT and the increase in immobility time in the TST and FST in mice. Pretreatment with minocycline to inhibit the innate immune response was able to abolish the reversal effect of post-stress injection of amphotericin B liposomes on CSDS-induced behavioral abnormalities and the prophylactic effect of pre-stress injection of amphotericin B liposomes on CSDS-induced behavioral abnormalities. These results demonstrate that amphotericin B liposomes have both therapeutic and prophylactic effects on chronic stress-induced behavioral abnormalities in mice by mobilizing the innate immune response.

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Novel rapid-acting glutamatergic modulators: Targeting the synaptic plasticity in depression

Cited by 44 publications

References 237 publications

Identification of 64 new risk loci for major depression, refinement of the genetic architecture and risk prediction of recurrence and comorbidities

Identification of 64 new risk loci for major depression, refinement of the genetic architecture and risk prediction of recurrence and comorbidities

Melatonin: From Neurobiology to Treatment

Therapeutic and Prophylactic Effects of Amphotericin B Liposomes on Chronic Social Defeat Stress-Induced Behavioral Abnormalities in Mice

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