Enhanced Cognition and Neurogenesis in miR-146b Deficient Mice

Cells, Год журнала: 2022, Номер 11(13), С. 2002 - 2002

Опубликована: Июнь 22, 2022

The miR-146 family consists of two microRNAs (miRNAs), miR-146a and miR-146b, which are both known to suppress a variety immune responses. Here in this study, we show that miR-146b is abundantly expressed neuronal cells, while mainly microglia astroglia adult mice. Accordingly, deficient (Mir146b-/-) mice exhibited anxiety-like behaviors enhanced cognition. Characterization cellular composition Mir146b-/- using flow cytometry revealed an increased number neurons decreased abundancy the hippocampus frontal cortex, whereas remained unchanged. Immunohistochemistry showed higher density cortex mice, hippocampal neurogenesis as evidenced by proliferation, survival newly generated cells with maturation into phenotype. No microglial activation or signs neuroinflammation were observed Further analysis demonstrated deficiency associated elevated expression glial cell line-derived neurotrophic factor (Gdnf) mRNA hippocampus, might be at least part responsible for expansion behavioral This hypothesis partially supported positive correlation between performance object recognition test Gdnf Together, these results distinct function controlling provide new insights understanding cell-specific astroglial organization mouse brain.

Язык: Английский

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Glial receptor PLXNB2 regulates schizophrenia-related stress perception via the amygdala

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Окт. 17, 2022

Stress is a trigger for the development of psychiatric disorders. However, how stress trait differs in schizophrenia patients still unclear. also induces and exacerbates immune activation Plexins (Plxn) its ligands semaphorins (Sema) are important cellular receptors with plural functions both brain system. Recently, role Plxn/Sema regulation neuroinflammation was noticed. Here, when investigating mechanisms underlying susceptibility schizophrenia, we discovered Plxnb2 response. Patients first-episode (FES) high (FES-hs, n =51) low (FES-ls, =50) perception healthy controls (HCs) ( =49) were first recruited neuroimaging blood bulk RNA sequencing (RNA-seq). A mouse model chronic unpredictable (CUS) intra-amygdaloid functional blocking further explored to depict target gene functions. Compared HCs, FES-hs had bigger caudate thalamus (FDR=0.02&0.001, respectively) whereas FES-ls smaller amygdala (FDR=0.002). Blood RNA-seq showed differentially expressed PLXNB2 among patient groups HCs (FDR<0.05~0.01). Amygdaloid size level negatively correlated p <0.01&0.05, respectively), which fully mediated amygdaloid positive association expression (β=0.9318, 95% CI: 0.058~1.886) patients. In mice, enriched astrocytes microglia CUS reduced <0.05). Inhibition by monoclonal antibody (mAb)-102 induced mice anxiety <0.05), enlargement microglial ramification <0.001) compared saline. These data suggest that regulates amygdala-dependent responses.

Язык: Английский

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Prenatal Immune Challenge Differentiates the Effect of Aripiprazole and Risperidone on CD200–CD200R and CX3CL1–CX3CR1 Dyads and Microglial Polarization: A Study in Organotypic Cortical Cultures

Life, Год журнала: 2024, Номер 14(6), С. 721 - 721

Опубликована: Июнь 2, 2024

Microglia are the primary innate immune cells of central nervous system and extensively contribute to brain homeostasis. Dysfunctional or excessive activity microglia may be associated with several neuropsychiatric disorders, including schizophrenia. Therefore, we examined whether aripiprazole risperidone could influence expression Cd200–Cd200r Cx3cl1–Cx3cr1 axes, which crucial for regulation microglial interactions these neurons. Additionally, evaluated impact drugs on pro- anti-inflammatory markers (Cd40, Il-1β, Il-6, Cebpb, Cd206, Arg1, Il-10 Tgf-β) cytokine release (IL-6, IL-10). The research was executed in organotypic cortical cultures (OCCs) prepared from offspring control rats (control OCCs) those exposed maternal activation (MIA OCCs), allows exploration schizophrenia-like disturbances animals. All experiments were performed under basal conditions after additional stimulation lipopolysaccharide (LPS), following “two-hit” hypothesis We found that MIA diminished mRNA level Cd200r affected OCCs’ response LPS exposure terms this parameter. downregulated Cx3cr1 profoundly changed levels both types OCCs. Risperidone increased Cd200 OCCs, while treatment elevated gene dyad antipsychotics limited LPS-generated increase proinflammatory factors (Il-1β Il-6) enhanced components (Cd206 polarization, mostly absence procedure. Finally, observed a more pronounced modulating cytokines when compared In conclusion, our data suggest might crosstalk neurons, whereas beneficially affect changes

Язык: Английский

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Effects of social dominance and acute social stress on morphology of microglia and structural integrity of the medial prefrontal cortex

Brain Behavior and Immunity, Год журнала: 2024, Номер 122, С. 353 - 367

Опубликована: Авг. 24, 2024

Язык: Английский

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CSF1R regulates schizophrenia-related stress response and vascular association of microglia/macrophages

BMC Medicine, Год журнала: 2023, Номер 21(1)

Опубликована: Авг. 4, 2023

Microglia are known to regulate stress and anxiety in both humans animal models. Psychosocial is the most common risk factor for development of schizophrenia. However, how microglia/brain macrophages contribute schizophrenia not well established. We hypothesized that effector molecules expressed microglia/macrophages were involved via regulating susceptibility.We recruited a cohort first episode (FES) patients (n = 51) age- sex-paired healthy controls (HCs) 46) with evaluated perception. performed blood RNA-sequencing (RNA-seq) brain magnetic resonance imaging, measured plasma level colony stimulating 1 receptor (CSF1R). Furthermore, we studied mouse model chronic unpredictable (CUS) combined CSF1R inhibitor (CSF1Ri) 9 ~ 10/group) on behaviours microglial biology.FES showed higher scores perceived scale (PSS, p < 0.05), lower mRNA (FDR 0.003) protein (p 0.05) levels, smaller volumes superior frontal gyrus parahippocampal (both FDR than HCs. In RNA-seq, CSF1R-associated differentially genes related development. Importantly, facilitated negative association PSS 0.01) HCs but FES patients. CUS+CSF1Ri model, similarly as CUS, CSF1Ri enhanced 0.001). Genes angiogenesis intensity CD31+-blood vessels dampened after CUS-CSF1Ri treatment. preferentially diminished juxta-vascular induced morphological changes (all 0.05).Microglial/macrophagic regulated schizophrenia-associated angiogenesis.

Язык: Английский

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Paradoxical attenuation of neuroinflammatory response upon LPS challenge in miR-146b deficient mice

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Окт. 31, 2022

The miR-146 family consists of two microRNAs (miRNAs), miR-146a and miR-146b (miR-146a/b), both which are known to suppress immune responses in a variety conditions. Here, we studied how constitutive deficiency ( Mir146b-/- ) affects lipopolysaccharide (LPS)-induced neuroinflammation mice. Our experiments demonstrated that results the attenuation LPS-induced neuroinflammation, as it was evidenced by reduction sickness behavior, decrease inflammatory status microglia, loss morphological signs microglial activation hippocampus. Gene expression analysis revealed upregulation hippocampal pro-inflammatory cytokines is attenuated mice, compared wild-type WT In addition, reduced NF-κB nuclear protein p65, target TLR4 relatively stronger miR- 146a found mice upon LPS challenge. Compensatory can explain neuroinflammation. This supported conducted with miR-146a/b deficient Mir146a/b-/- ), additional deletion led restoration behavior proinflammatory cytokines. also showed observed due overexpression transcription inducer, interferon regulatory factor 7 Irf7 ). Altogether, our show existence crosstalk between mir-146b regulation

Язык: Английский

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Succinum extracts inhibit microglial-derived neuroinflammation and depressive-like behaviors

Frontiers in Pharmacology, Год журнала: 2022, Номер 13

Опубликована: Авг. 16, 2022

Microglia are emerging as important targets for the treatment of neuropsychiatric disorders. The phagocytic microglial phenotype and resulting neuroinflammation lead to synaptic loss neuronal cell death. To explore potential candidates that inhibit hyperactivation, we first investigated ten candidate extracts traditional Chinese medicine (TCM) using lipopolysaccharide (LPS)-stimulated BV2 cells. Among candidates, Pinus spp. succinum extract (PSE) was superior; thus, further its pharmacological activity underlying mechanisms both in vitro vivo . Pretreatment with PSE (10, 20, 40 μg/ml) attenuated increases inflammatory factors (nitric oxide tumor necrosis factor-α), translocation nuclear factor-kappa B (NF-κB), phenotypic transformations (phagocytic migratory) a dose-dependent manner. These inhibitory effects on microglia were supported by regulatory CX 3 C chemokine receptor 1 (CX CR1)/nuclear factor erythroid-2-related 2 (Nrf2) pathway. In particular, intragastric administration (100 mg/kg) considerably improved sickness, anxiety, depressive-like behaviors mice subjected chronic restraint stress (CRS). Our results suggest has strong antineuroinflammatory antidepressant properties, may involve not only regulation NF-κB but also normalization CR1/Nrf2

Язык: Английский

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Probiotic Bactolac Provides Antidepressant Effect by Increasing BDNF level and Reducing NLRP3 and MC4R Expression Levels, Neuron Damage, Glial Activity and Depression-Like Behaviors in Rats

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Март 12, 2024

Aim:Chronic stress plays an important role in the pathophysiology of depression. In this study, we aimed to investigate therapeutic effects Bactolac (Lactobacillus plantarum NBIMCC 8767+Streptococcus thermophilus 8258) on chronic stress-induced depression rats. Methods:This study was performed a total 28 rats, control (C), (S), (B), Bactolac+stress (BS) groups (each n=7). Behavioral tests were evaluate depressive behaviors (sucrose preference test, three-chamber sociability elevated plus maze forced swim test). 5-HT1A, DRD1, ADRA-2A, GABA-A α1, CNR1, NR3C2, NLRP3, MC4R expression levels hippocampus tissue; NOD1 receptor small intestine tissue determined by RT-PCR method. BDNF elisa kit. Histopathological examinations cortex and tissues. Results:Bactolac treatment reduced depressive-like (p<0.05), NLRP3 neurodegeneration, glial activity, increased levels. It had no effect other parameters examined stressed Conclusions:Chronic decreased level; MC4R, caused neurodegeneration ultimately led effects. effective reducing may be natural agent for

Язык: Английский

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Priming of hippocampal microglia by IFN-γ/STAT1 pathway impairs social memory in mice

International Immunopharmacology, Год журнала: 2024, Номер 134, С. 112191 - 112191

Опубликована: Май 16, 2024

Язык: Английский

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Post-weaning social isolation alters sociability in a sex-specific manner

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 13, 2024

Abstract Adolescence is a critical period for brain development in humans and stress exposure during this time can have lasting effects on behavior development. Social isolation loneliness are particularly salient stressors that lead to detrimental mental health outcomes females, although most of the preclinical work social has been done male animals. Our lab developed model post-weaning adolescent leads increased drug reward sensitivity altered neuronal structure limbic regions. The current study utilized determine impact three-chamber interaction task both adolescence adulthood. We found while does not alter (PND45), it sex-specific adulthood (PND60), potentiating mice decreasing female mice. As early life activate microglia leading alterations pruning, we next examined inhibiting microglial activation with daily minocycline administration first three weeks these changes interaction. During adolescence, dampened mice, having no effect females. In contrast, adulthood, did males, socially isolated males exhibiting higher levels compared their group housed counterparts. treatment reversed group, mimicking what seen naïve males. Taken together, alters but

Язык: Английский

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