Neuroreport最新文献

Objective: Acute stress enhances the activity of magnocellular neurons (MNs) by inducing long-term changes in excitatory inputs. We aim to investigate the mechanism underlying long-term potentiation (LTP) of glutamatergic inputs to paraventricular nucleus (PVN) MNs in stressed rats.

Methods: Rats were subjected to multiple stressors and randomly assigned to control and stress groups. In some experiments, stressed rats received intracerebroventricular (i.c.v.) injections of the β-adrenergic receptor (AR) antagonist or the β1-AR antagonist. Excitatory postsynaptic currents evoked by electrical stimulation in hypothalamic slices were recorded from PVN MNs using an Axopatch 200B amplifier. LTP of glutamatergic inputs to MNs was induced by electrical stimulation trains (100 Hz, 100 pulses, three times). Biocytin staining and immunohistochemistry were used to characterize the morphology of recorded neurons and detect β1-AR expression.

Results: Blockade of gamma-aminobutyric acid receptor, tetanic stimulation-induced glutamatergic LTP in MNs of nonstressed rats, which was significantly augmented in stressed rats. Blocking N-methy-D-aspartate receptors abolished LTP in nonstressed rats but revealed a novel LTP in stressed rats. I.c.v. administration of propranolol, or CGP 20712, before the stress procedure abolished this novel LTP in stressed rats. In contrast, administration of norepinephrine or a selective β1-AR agonist, dobutamine triggered the novel LTP in nonstressed rats. The novel LTP in stressed rats was abolished by intracellular inhibition of protein kinase A (PKA). β1-AR immunoreactivity was detected in PVN MN areas.

Conclusion: Acute stress enhances the β1-AR/PKA signaling, leading to long-term modifications of glutamatergic inputs in the hypothalamic PVN MNs in rats in vivo.

Background: Recent evidence suggests that neuroinflammation and synaptic dysfunction play crucial roles in linking obesity to the development of depression. Long-term consumption of a high-fat (HF) diet not only leads to metabolic disruptions in the body but also disturbs brain homeostasis, particularly affecting the amygdala, a key region involved in regulating depression.

Methods: This study explored the therapeutic potential of geniposide, a bioactive iridoid glycoside known for its antiinflammatory properties, in mitigating HF diet-induced depressive behaviors and amygdala pathology.

Results: Geniposide supplementation significantly improved HF diet-induced depression, as assessed through various behavioral tests including the open field test, forced swimming test, elevated plus maze test, and tail suspension test. Geniposide demonstrated notable synaptic protective effects, evidenced by an increase in the length of the active zone and postsynaptic density thickness, as well as a decrease in the synaptic cleft in the amygdala of HF diet-fed mice. Additionally, geniposide suppressed microglial activation, downregulated the expression of pro-inflammatory cytokines [interleukin (IL)-1β, tumor necrosis factor alpha (TNF-α), IL-6], and reduced C3/C1q expression. Furthermore, geniposide administration markedly decreased the colocalization of C1q, a microglia-derived complement component, with postsynaptic density protein 95-positive puncta in the amygdala.

Conclusion: In summary, this study demonstrates that geniposide alleviates HF diet-induced depressive behaviors, which is associated with improved synaptic health and reduced neuroinflammation in the amygdala. These findings provide a mechanistic basis for the potential repurposing of geniposide in the management of obesity-related affective disorders.

Objective: This study investigates the role of pleckstrin homology-like domain family A member 1 (PHLDA1) in traumatic brain injury (TBI) and examines how its knockdown may mitigate neurological impairments associated with TBI, focusing on mitochondrial dysfunction, neuro-inflammation, and oxidative stress.

Methods: TBI was induced in rats, and PHLDA1 expression was assessed through qPCR and Western blot. Neurological functions were evaluated via grip strength, balance beam, and rotarod tests. Brain tissue samples were analyzed for edema, apoptosis, and mitochondrial activity. Additionally, the effects of PHLDA1 knockdown on protein kinase B/nuclear factor erythroid 2-related factor 2/sirtuin 3 (AKT/Nrf2/Sirt3) signaling were examined in H 2 O 2 -treated PC12 cells, with the AKT inhibitor MK-2206 used to explore pathway interactions.

Results: PHLDA1 levels were elevated in TBI rats, correlating with impaired neurological function, brain edema, and increased cell apoptosis. PHLDA1 knockdown improved motor performance, reduced edema, decreased apoptotic cell counts, and alleviated inflammation. Furthermore, it restored mitochondrial membrane potential and increased ATP production. In cell models, PHLDA1 knockdown reduced oxidative stress and enhanced AKT/Nrf2/Sirt3 pathway activation, which MK-2206 partially reversed. Additional experiments indicated that EZH2 inhibited PHLDA1 transcription by binding to its promoter.

Conclusion: PHLDA1 knockdown mitigates TBI-induced neurodegeneration by reducing oxidative stress and enhancing mitochondrial function through the AKT/Nrf2/Sirt3 pathway. These findings suggest that targeting PHLDA1 may offer a novel therapeutic approach for TBI.

Background: Transient global cerebral ischemia induces selective neuronal death, with pyramidal neurons in the hippocampal CA1 region degenerating while CA3 neurons remain intact. Although dendritic and spine alterations in CA1 neurons postischemia have been extensively studied, the morphological changes in surviving CA3 neurons remain poorly understood.

Methods: Using Golgi staining and three-dimensional reconstruction in a rat four-vessel occlusion ischemia model, we examined dendritic and spine dynamics in CA3 neurons. In addition, P0 cultured hippocampal neurons transfected with green fluorescent protein (GFP) were exposed to oxygen-glucose deprivation (OGD) in vitro , and dendritic morphological changes were monitored longitudinally.

Results: Transient ischemia triggered apical dendritic retraction in CA3 neurons 48 h post-injury, while basal dendrites remained unaffected. Apical dendritic branching also decreased at this time point. Spine density transiently increased at 12 and 24 h before normalizing by 48 h, with no significant shift in spine type proportions. In-vitro, surviving primary hippocampal neurons showed delayed dendritic shortening post-OGD, whereas degenerating neurons exhibited early dendritic elongation.

Conclusion: Surviving CA3 pyramidal neurons exhibit greater adaptability to ischemic stress compared with vulnerable CA1 neurons, possibly explaining their differential survival. Pharmacological stabilization of neuronal morphology may offer a promising therapeutic strategy for ischemic stroke.

Background: The mechanism of electroacupuncture (EA) pretreatment for cerebral ischemia-reperfusion injury (CIRI) is unclear. This study aimed to investigate whether EA pretreatment attenuates CIRI through the miR-124/nuclear factor kappa B (NF-κB)/Fas signaling pathway.

Methods: Following 7 days of EA pretreatment at Baihui (GV20), Fengfu (GV16), and Dazhui (GV14), CIRI rats were established. Neuroprotection was assessed using modified neurological severity score (mNSS), 2,3,5-triphenyltetrazolium chloride staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Neuronal ultrastructure was examined by electron microscopy. Immunofluorescence staining revealed pNF-κB and Fas expression patterns. Western blotting and real-time quantitative PCR were employed to quantify miR-124, NF-κB repressing factor (NKRF), pNF-κB/NF-κB ratio, Fas, FasL, fas-associated protein with death domain (FADD), caspase-3, and caspase-8 in the cerebral cortex.

Results: EA pretreatment reduced cerebral infarction volume, alleviated mNSS and cortical neuronal apoptosis. Moreover, EA pretreatment downregulated miR-124, pNF-κB/NF-κB/Fas, FasL, FADD levels and increased NKRF expression. The effect of EA pretreatment was enhanced by miR-124 inhibitor.

Conclusion: These findings suggest that EA pretreatment attenuated neuronal apoptosis through suppression of the miR-124/NF-κB/Fas signaling pathway in CIRI.

Background: Perimenopausal depression (PMD), a psychiatric disorder triggered by declining ovarian function before menopause, remains poorly understood in terms of therapeutic mechanisms. While acupuncture has demonstrated efficacy in alleviating PMD symptoms, its molecular basis requires further exploration. This study aimed to investigate whether acupuncture ameliorates PMD by modulating phosphatidylinositol 3-kinase (PI3K)/serine-threonine protein kinase (AKT)/mammalian target of rapamycin (mTOR) signaling in a rat model.

Methods: The female SD rats were randomly assigned to four groups: model, blank, acupuncture, and Western medicine, with each group consisting of six rats. The acupuncture group received acupuncture at the Baihui (GU20), Shenshu (BL23), Ganshu (BL18), and Sanyinjiao points for 28 consecutive sessions over 4 weeks. A PMD rat model was established through ovariectomy (OVX) combined with chronic unpredictable mild stress. Depression-related behaviors were measured through the forced swimming test, sucrose preference test, and open field test. The levels of estrogen (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and gonadotropin-releasing hormone (GnRH) in serum were determined through ELISA. The expression of PI3K, AKT, and mTOR in the hippocampal Cornu Ammonis 1 (CA1) region was analyzed by reverse transcription quantitative PCR and Western blotting.

Results: Acupuncture markedly attenuated depression-like behaviors and hippocampal pathology in PMD rats. It restored hormonal balance by elevating serum E2 while suppressing FSH, LH, and GnRH. At the molecular scale, acupuncture enhanced the expression of both mRNA and proteins of PI3K, AKT, and mTOR in the hippocampus CA1 region.

Conclusion: Acupuncture alleviates PMD through dual regulation of sex hormone homeostasis and activation of the PI3K/AKT/mTOR pathway, suggesting a potential mechanism for its antidepressant effects in perimenopause.

Background: Peripheral nerve injury (PNI) leads to substantial functional impairment, yet current therapies remain limited. Electroacupuncture (EA) is a promising intervention for PNI, but its mechanisms, particularly its role in modulating energy metabolism during nerve regeneration, are poorly understood.

Methods: A mouse PNI model was established by crushing the right sciatic nerve. EA stimulation was applied on the right side acupoints of Huantiao (GB30) and Zusanli (ST36) in PNI mice. Hind-limb splaying and gait analysis were used to evaluate motor function, and electrophysiological tests were used to assess nerve conduction. Nerve regeneration and molecular mechanisms were examined by Western blot, immunofluorescence, and transmission electron microscopy.

Results: We found that EA treatment significantly improved motor function, increased compound muscle action potential amplitude, and reduced muscle atrophy. Axonal regeneration was accelerated, as evidenced by increased SCG10-positive fibers. EA increased mitochondrial transcription factor A, mitochondrial DNA copy number, and mitochondrial electron transport chain activity, indicative of improved mitochondrial function and oxidative phosphorylation. Moreover, EA was identified to enhance energy metabolism by upregulating neurotrophic factors and modulating the AMPK/mTOR/p70S6K pathway.

Conclusion: Our findings indicate that EA at Huantiao (GB30) and Zusanli (ST36) promotes nerve regeneration and functional recovery after PNI by upregulating energy metabolism. This study provides a novel perspective on the therapeutic potential of EA in peripheral nerve repair.

Background: Prenatal alcohol exposure (PAE) is recognized as the leading cause of adverse prenatal exposure disorders worldwide. The neurodevelopmental impairments resulting from PAE in offspring are classified under fetal alcohol syndrome (FAS). Nonetheless, the precise underlying pathogenic mechanisms of FAS remain incompletely understood, and effective therapeutic interventions are currently lacking. Notably, the antioxidant astaxanthin has demonstrated significant neuroprotective properties.

Methods: In this study, we established a C57BL/6J mouse model of FAS and administered potential therapeutic doses of astaxanthin through oral gavage. We evaluated the dual effects of ethanol exposure and astaxanthin intervention on oxidative stress, cognitive development, and cellular apoptosis in FAS. Furthermore, using molecular detection and plasmid transfection, we validated the regulatory cascade between the transcription factor Maf and the antiapoptotic protein B-cell lymphoma 2 (Bcl2), demonstrating the therapeutic efficacy and mechanism of astaxanthin against FAS.

Results: The results demonstrate that prenatal alcohol exposure induces neuronal oxidative damage and cognitive developmental impairments, concomitant with reduced expression of the transcription factor Maf in the brain and consequent suppression of antiapoptotic Bcl2 activity. Strikingly, astaxanthin administration significantly attenuated alcohol-induced reactive oxygen species accumulation and restored both Maf and Bcl2 expression levels. This intervention effectively ameliorated neuronal apoptosis and neurodevelopmental abnormalities.

Conclusion: These findings reveal that astaxanthin alleviates FAS-related pathophysiology by rescuing the alcohol-disrupted Maf-Bcl2 axis, consequently reducing neuronal cell death. This study provides novel mechanistic insights into FAS pathogenesis and identifies a promising therapeutic strategy.

Objectives: Accumulating evidence indicates distinct differences in static brain activity between eyes-open (EO) and eyes-closed (EC) resting states. However, whether dynamic alterations in intrinsic brain activity are significantly associated with ocular states remains unsubstantiated. This study aimed to investigate state-dependent modulations of dynamic intrinsic brain activity across EO and EC conditions through dynamic amplitude of low-frequency fluctuation (dALFF) - a methodological framework integrating conventional amplitude of low-frequency fluctuation metrics with sliding-window analytical approaches.

Methods: A cohort of 26 subjects (13 males and 13 females) was demographically matched by age, sex, and educational attainment. The dALFF values across brain regions were calculated for both EO and EC states using sliding-window analysis, with subsequent comparison of dynamic brain activity between these ocular conditions.

Results: Relative to the EC condition, the EO state exhibited reduced dALFF values in the left Parietal Inf. Conversely, elevated dALFF values were observed in the left Cerebellum 6, left Fusiform, the left and right Occipital Mid, and right Precentral during EO compared to EC.

Conclusion: Our principal findings revealed significantly heightened neural activity in the left Cerebellum 6, left Fusiform, the left and right Occipital Mid, and right Precentral during EO compared to EC resting states. Conversely, diminished dALFF was identified in the left Parietal Inf under EO conditions. These differential activation patterns collectively suggest that intrinsic brain dynamics are substantially modulated by visuomotor state transitions, particularly involving ocular status alterations.

Objective: The visual cortex plays a crucial role in integrating multiple stimulus features, such as orientation tuning and spatial frequency tuning , to form coherent perceptual representations of the visual environment. Although previous research has hinted at the presence of overlapping maps for orientation and spatial frequency tuning in the visual cortex, clear evidence demonstrating how these features are jointly organized functionally is scarce.

Methods: To address this, we performed multiunit electrophysiological recordings in the primary visual cortex (V1) of anesthetized cats. We presented visual stimuli consisting of drifting sine-wave gratings under two experimental conditions: varying the orientation while keeping spatial frequency constant and varying spatial frequency while maintaining fixed orientations at 0° or 90°. Neuronal responses were analyzed by fitting tuning curves to quantify preferred orientations and spatial frequencies. Functional connectivity between neurons was then assessed using cross-correlogram analysis.

Results: Our results showed that neurons with similar orientation and spatial frequency tuning, exhibited significantly stronger connectivity at 0° orientation, whereas this effect was not observed at 90°. These results indicate that the organization of neuronal networks in V1 is stimulus-dependent and that overlapping ensembles encode these features in a coordinated manner. These results are important for understanding how complex features are integrated within the visual system, and more broadly, how the brain processes and combines information.

Conclusion: Such feature-based connectivity likely enhances the visual cortex's ability to efficiently process complex stimuli, supporting the idea that perceptual integration relies on the dynamic interplay of neurons sharing similar tuning properties.