Maternal Inflammation and Neurodevelopmental Programming: A Review of Preclinical Outcomes and Implications for Translational Psychiatry

Biological Psychiatry, Journal Year: 2018, Volume and Issue: 85(2), P. 107 - 121

Published: Aug. 27, 2018

Language: Английский

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Magnetoelectric Nanoparticles Incorporated Biomimetic Matrix for Wireless Electrical Stimulation and Nerve Regeneration

Advanced Healthcare Materials, Journal Year: 2021, Volume and Issue: 10(16)

Published: June 27, 2021

Abstract Electrical stimulation is regarded pivotal to promote repair of nerve injuries, however, failed get extensive application in vivo due the challenges noninvasive electrical loading accompanying with construction biomimetic cell niche. Herein, a new concept magneto responsive electric 3D matrix for remote and wireless demonstrated. By preparation magnetoelectric core/shell structured Fe 3 O 4 @BaTiO NPs‐loaded hyaluronan/collagen hydrogels, which recapitulate considerable magneto‐electricity vital features native neural extracellular matrix, enhancement neurogenesis both cellular level spinal cord injury external pulsed magnetic field applied proved. The findings pave way novel class controlling delivering electricity through niches‐mimicked hydrogel network, arising prospects not only but also human–computer interaction higher resolution.

Language: Английский

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Recent advances on the molecular mechanisms of exercise-induced improvements of cognitive dysfunction

Translational Neurodegeneration, Journal Year: 2023, Volume and Issue: 12(1)

Published: Feb. 27, 2023

Abstract Physical exercise is of great significance for maintaining human health. Exercise can provide varying degrees benefits to cognitive function at all stages life cycle. Currently, with the aging world’s population and increase expectancy, dysfunction has gradually become a disease high incidence, which accompanied by neurodegenerative diseases in elderly individuals. Patients often exhibit memory loss, aphasia weakening orientation once diagnosed, are unable have normal life. Cognitive largely affects physical mental health, reduces quality life, causes economic burden society. At present, most interventions aimed maintain current level delay deterioration cognition. In contrast, as nonpharmacological therapy advantages its nontoxicity, low cost universal application. The molecular mechanisms underlying effect on cognition complex, studies been extensively centered neural plasticity, direct target brain. addition, mitochondrial stability energy metabolism essential brain status. Meanwhile, organ-brain axis responds induces release cytokines related this review, we summarize latest evidence effects cognition, point out directions future research.

Language: Английский

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Curcumin reverses cognitive deficits through promoting neurogenesis and synapse plasticity via the upregulation of PSD95 and BDNF in mice

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 7, 2025

Following prolonged exposure to hypoxic conditions, for example, due ascent high altitude, aging or stroke, cognitive deficits can develop. The exact nature and genesis of hypoxia-induced remain unresolved. Curcumin has been reported stimulate neurogenesis reduce neuronal degeneration. This study aimed investigate the effect curcumin on in hypoxic-brain injury mice its potential mechanism. Eight-week-old male C57BL/6J were normobaric-hypoxia (13%O2) 14 days establish models. Morris water maze novel object recognition used detect function each mouse. Immunofluorescence assays, including Fluoro-Jade C (FJC) bromodeoxyuridine (BrdU), degeneration neurogenesis. Thy1-YFP transgenic synapse plasticity. Our results showed that administration rescued impaired cognition mice, shown as enhanced BrdU+ dendritic spine hippocampus. At molecular level, was found promote expression brain-derived neurotrophic factor (BDNF) postsynaptic density protein 95 (PSD95). primary hippocampal neuron detection could growth. In conclusion, our indicates curcumin, increased BDNF PSD95 contacted with interneurons, salvaged interneurons may normalize ambient neuroplasticity, resulting preservation processes well contributing improve performance.

Language: Английский

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Synapse Pathology in Schizophrenia: A Meta-analysis of Postsynaptic Elements in Postmortem Brain Studies

Schizophrenia Bulletin, Journal Year: 2019, Volume and Issue: unknown

Published: May 13, 2019

Changed synapse density has been suggested to be involved in the altered brain connectivity underlying schizophrenia (SCZ) pathology. However, postmortem studies addressing this topic are heterogeneous and it is not known whether changes restricted specific regions. Using meta-analysis, we systematically quantitatively reviewed literature on of postsynaptic elements tissue patients with SCZ compared healthy controls. We included 3 outcome measurements for elements: dendritic spine (DSD), (PSD) number, PSD protein expression levels. Random-effects meta-analysis (31 studies) revealed an overall decrease (Hedges's g: −0.33; 95% CI: −0.60 −0.05; P = .020). Subgroup analyses showed reduction cortical but subcortical tissues −0.44; −0.76 −0.12; .008, Hedges's −0.11; −0.54 0.35; .671) specifically a measure DSD −0.81; −1.37 −0.26; .004). Further exploratory significant prefrontal cortex layer 3. In all analyses, substantial heterogeneity was present. Meta-regression no influence age, sex, interval, or bank effect size. This shows region-specific SCZ. phenotype provides important cellular hallmark future preclinical neuropathological research order increase our understanding dysconnectivity

Language: Английский

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Inhibition of NADPH oxidase by apocynin prevents learning and memory deficits in a mouse Parkinson's disease model

Redox Biology, Journal Year: 2019, Volume and Issue: 22, P. 101134 - 101134

Published: Feb. 10, 2019

The activation of NADPH oxidase contributes to dopaminergic neurodegeneration and motor deficits in Parkinson's disease (PD). However, whether is involved non-motor symptoms, especially cognitive dysfunction PD remains unknown. This study undertaken characterize the effects inhibition by a widely used inhibitor apocynin on learning memory paraquat maneb-induced mouse model. Results showed that mice injected with maneb displayed impairments spatial memory, which was associated reduced tyrosine hydroxylase expression as well increased neurodegeneration, synaptic loss, α-synuclein Ser129-phosphorylation hippocampus. Interestingly, treatment significantly ameliorated hippocampal pathology treated these two pesticides. Mechanistically, we found mitigated related oxidative stress. Furthermore, microglial M1 polarization were observed co-treated compared alone group. Finally, inhibited signal transducers activators transcription 1 (STAT1) nuclear factor kappa B (NF-κB) pathways, key regulatory factors for inflammatory responses, maneb-treated mice. Altogether, our findings implied mediates PD, blocks via suppression stress neuroinflammation.

Language: Английский

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PSD-95 deficiency disrupts PFC-associated function and behavior during neurodevelopment

Scientific Reports, Journal Year: 2019, Volume and Issue: 9(1)

Published: July 1, 2019

Abstract Postsynaptic density protein-95 (PSD-95) is a major regulator in the maturation of excitatory synapses by interacting and trafficking N-methyl-D-aspartic acid receptors (NMDAR) α-amino-3-hydroxy-5-methyl-4-isox-azoleproprionic (AMPAR) to postsynaptic membrane. PSD-95 disruption has recently been associated with neuropsychiatric disorders such as schizophrenia autism. However, effects deficiency on prefrontal cortex (PFC)-associated functions, including cognition, working memory, sociability, yet be investigated. Using knockout mouse model (PSD-95 −/− ), we examined how affects NMDAR AMPAR expression function medial (mPFC) during juvenile adolescent periods development. We found significant increases total protein levels subunits GluN1, GluN2B, accompanied decreases subunit GluA1 adolescence. Correspondingly, there increase NMDAR/AMPAR-mediated current amplitude ratio that progresses from juvenile-to-adolescence. Behaviorally, mice exhibit lack well learning memory deficits. Together, our data indicate disrupts mPFC synaptic related behavior at critical age This study highlights importance neurodevelopment its potential link pathogenesis and/or

Language: Английский

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AMPA receptors and their minions: auxiliary proteins in AMPA receptor trafficking

Cellular and Molecular Life Sciences, Journal Year: 2019, Volume and Issue: 76(11), P. 2133 - 2169

Published: April 1, 2019

To correctly transfer information, neuronal networks need to continuously adjust their synaptic strength extrinsic stimuli. This ability, termed plasticity, is at the heart of function and is, thus, tightly regulated. In glutamatergic neurons, controlled by number AMPA receptors postsynapse, which mediate most fast excitatory transmission in central nervous system. Their trafficking to, at, from synapse, therefore, a key mechanism underlying plasticity. Intensive research over last 20 years has revealed increasing importance interacting proteins, accompany throughout lifetime help refine temporal spatial modulation function. this review, we discuss current knowledge about roles partners regulating receptor focus especially on movement between intracellular, extrasynaptic, pools. We examine involvement not only basal function, but also Hebbian homeostatic Included our review are well-established interactants such as GRIP1 PICK1, classical auxiliary subunits TARP CNIH, newest additions native complexes.

Language: Английский

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PSD-95: An Effective Target for Stroke Therapy Using Neuroprotective Peptides

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(22), P. 12585 - 12585

Published: Nov. 22, 2021

Therapies for stroke have remained elusive in the past despite great relevance of this pathology. However, recent results provided strong evidence that postsynaptic density protein-95 (PSD-95) can be exploited as an efficient target neuroprotection by strategies able to counteract excitotoxicity, a major mechanism neuronal death after ischemic stroke. This scaffold protein is key maintenance complex framework interactions established at (PSD) excitatory neurons, relevant function and survival. Using cell penetrating peptides (CPPs) therapeutic tools, two different approaches been devised advanced levels clinical development. First, nerinetide (Phase 3) AVLX-144 1) were designed interfere with coupling ternary formed PSD-95 GluN2B subunits N-methyl-D-aspartate type glutamate receptors (NMDARs) nitric oxide synthase (nNOS). These reduced neurotoxicity derived from NMDAR overactivation, decreased infarct volume improved neurobehavioral models important caveat approach was processing calpain, pathological specifically induced excitotoxicity profound alteration survival signaling. Thus, third peptide (TP95414) has recently developed cleavage reduce death, which also improves neurological outcome preclinical mouse model permanent ischemia. Here, we review advancements development characterization PSD-95-targeted CPPs propose combination these improve treatment other excitotoxicity-associated disorders.

Language: Английский

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Increased levels of the synaptic proteins PSD-95, SNAP-25, and neurogranin in the cerebrospinal fluid of patients with Alzheimer’s disease

Alzheimer s Research & Therapy, Journal Year: 2022, Volume and Issue: 14(1)

Published: April 23, 2022

Abstract Background There is currently a lack of reliable and easily accessible biomarkers predicting cognitive decline in Alzheimer’s disease (AD). Synaptic dysfunction loss occur early AD synaptic measured the brain tissue by PET are closely linked to decline, rendering proteins promising target for biomarker development. Methods We used novel Simoa assays measure cerebrospinal fluid (CSF) levels two candidates, postsynaptic density protein 95 (PSD-95/DLG4), presynaptically localized synaptosomal-associated 25 (SNAP-25), as well neurogranin (Ng), an established biomarker. CSF samples from well-characterized cohorts ( n =178 =156) were selected banked obtained diagnostic lumbar punctures containing subjects with amyloid-ß (Aß) positive AD, non-AD neurodegenerative diseases, other neurological conditions, healthy controls (HC). Results All had detectable PSD-95, SNAP-25, Ng. Ng all correlated, strongest correlation between presynaptic SNAP-25 neurogranin. on average higher concentrations three markers compared those disorders, HCs. Increased were, however, not specific present sporadic cases inflammatory or vascular disorders well. High PSD-95 also observed few disorders. Conclusion The data establishes marker pathology, while appear be somewhat more AD. Together, these hold promise identify correlate monitor responses disease-modifying drugs reducing degeneration.

Language: Английский

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