Neuroreport最新文献

Recent studies have shown that autophagy is activated in response to nerve damage and occurs simultaneously with the initial stages of Schwann cell-mediated demyelination. Although several studies have reported that macroautophagy is involved in the peripheral nerve, the role of chaperone-mediated autophagy (CMA) has not yet been investigated in peripheral nerve injury. The present study investigates the role of CMA in the sciatic nerve. Using a mouse model of sciatic nerve injury, the authors employed immunofluorescence analysis to observe the expression of LAMP2A, a critical marker for CMA. RNA sequencing was performed to observe the transcriptional profile of Lamp2a in Schwann cells. Bioinformatics analysis was carried out to observe the hub genes associated with Lamp2a . Expression of Lamp2a , a key gene in CMA, increased following sciatic nerve injury, based on an immunofluorescence assay. To identify differentially expressed genes using Lamp2a , RNA sequence analysis was conducted using rat Schwann cells overexpressing Lamp2a . The nine hub genes ( Snrpf, Polr1d, Snip1, Aqr, Polr2h, Ssbp1, Mterf3, Adcy6 , and Sbds ) were identified using the CytoHubba plugin of Cytoscape. Functional analysis revealed that Lamp2a overexpression affected the transcription levels of genes associated with mitotic spindle organization and mRNA splicing via the spliceosome. In addition, Polr1d and Snrpf1 were downregulated throughout postnatal development but elevated following sciatic nerve injury, according to a bioinformatics study. CMA may be an integral pathway in sciatic nerve injury via mRNA splicing.

Objective: Tyrosinase is a rate-limiting enzyme for the biosynthesis of melanin pigment in peripheral tissues, such as skin and the retina. We recently reported the expression and enzymatic activity of tyrosinase as well as its protective effects against oxidative stress-induced protein damage in the mouse brain. The functional role of tyrosinase in the central nervous system, however, remains largely unknown. In the present study, we investigated the involvement of tyrosinase in social behavior in mice.

Methods: Pigmented C57BL/10JMsHir (B10) and tyrosinase-deficient albino B10.C- Tyr c /Hir (B10-c) mice were subjected to the three-chamber sociability test to assess sociability and social novelty preference. In addition, we measured the mRNA expression of genes involved in catecholamine metabolism in the hippocampus by real-time quantitative PCR analysis.

Results: The results obtained showed that tyrosinase deficiency impaired social novelty preference, but not sociability in mice. We also found that the hippocampal expression of genes involved in catecholamine metabolism, such as monoamine oxidase A and catechol-O-methyltransferase , were significantly decreased in tyrosinase-deficient B10-c mice.

Conclusion: These results suggest that tyrosinase activity is functionally involved in the phenotypic expression of social behavior, particularly social novelty preference, in mice. The present study will advance our understanding of the functional role of tyrosinase in the central nervous system.

This study aims to investigate how electroacupuncture regulates the learning and memory abilities of poststroke cognitive impairment (PSCI) rats through the TLR4/NF-κB/NLRP3 signaling pathway on the hippocampal microglia. Thirty male rats were randomly divided into three groups: sham surgery group, PSCI model group, and electroacupuncture group, with 10 rats in each group. Middle cerebral artery occlusion was used to establish the PSCI model. The Zea Longa method was used to score the rats' neurological function. Electroacupuncture was utilized for 21 days to improve PSCI. The learning and memory abilities of rats were tested using the Morris water maze. Hematoxylin-eosin staining and immunofluorescence were used to find the hippocampus' pathological changes. The concentration of interleukin-1β, interleukin-6, tumor necrosis factor-α, and interleukin-18 were detected by ELISA. The mRNA expression levels of associated inflammatory corpuscles were measured by quantitative real-time PCR. The protein expression levels of TLR4, MyD88, NF-κB, and NLRP3 were measured using western blotting. Electroacupuncture improved not only the learning and memory abilities of PSCI rats but also hippocampal morphology. Electroacupuncture inhibited the activation of microglia and the TLR4/NF-κB/NLRP3 signaling pathway. Electroacupuncture also reduced proinflammatory factors and restrained the mRNA levels of NLRP3-associated inflammatory cytokines. Its mechanism was related to inhibiting the expression of the TLR4/NF-κB/NLRP3 signaling pathway, attenuating the release of inflammatory factors, and regulating the activation of hippocampal microglia in the brain.

To explore the differences in brain imaging in tinnitus with or without hearing loss (HL). We acquired functional MRI scans from 26 tinnitus patients with HL (tinnitus-HL), 24 tinnitus patients with no HL (tinnitus-NHL), and 26 healthy controls (HCs) matched by age and sex. The left and right thalamus were selected as seeds to study the endogenous functional connectivity (FC) of the whole brain, and its correlation with clinical indices was analyzed. Brain regions showing FC differences among the three groups included the Heschl gyrus (HES), right Hippocampus (HIP), right Amygdala (AMYG), left Calcarine fissure and surrounding cortex (CAL). Post hoc analysis showed that the thalamus-HIP connection and thalamus-lingual gyrus (LING) connection were enhanced in the tinnitus-NHL group, as compared to tinnitus-HL. Compared with HCs, the tinnitus-NHL group showed an enhanced connection between the thalamus and the left Inferior occipital gyrus, left CAL and LING. While in the tinnitus-HL group, the connection between the thalamus and several brain regions (right HES, right AMYG, etc) was weakened. In the tinnitus-HL group, the tinnitus handicap inventory scores were positively correlated with the FC of the left thalamus and right HES, right thalamus and right Rolandic operculum. The duration of tinnitus was negatively correlated with the FC of the right thalamus and right HIP. Abnormal FC in the thalamus may play an important role in the pathogenesis of tinnitus. Tinnitus-NHL and tinnitus-HL show different connection patterns, indicating that there are some differences in their pathogenesis.

This study explores the neural correlates between attentional control and trait anxiety among youth with a history of childhood maltreatment. Using diffusion tensor imaging, we investigated the microstructural integrity of brain white matter, particularly focusing on the right superior corona radiata (SCA-R). A total of 173 university students with experiences of childhood maltreatment underwent behavioral assessments using the Attentional Control Scale and trait anxiety measurements via the Spielberger State-Trait Anxiety Inventory. Our analysis found significant correlations between fractional anisotropy values in the SCA-R and trait anxiety levels, controlled for age and sex. Notably, SCA-R fractional anisotropy values partially mediated the relationship between attentional control and trait anxiety, suggesting a potential pathway through which attentional control could mitigate trait anxiety. These insights highlight attentional control as a potential mitigating factor against trait anxiety, particularly noting the partial mediation role of the SCA-R. Importantly, this study is descriptive and correlative, highlighting associations rather than causal relationships among the variables studied. These findings enhance our understanding of the neural mechanisms underlying anxiety in individuals with a history of childhood maltreatment.

Attention is a cognitive process that involves focusing mental resources on specific stimuli and plays a fundamental role in perception, learning, memory, and decision-making. Neurofeedback (NF) is a useful technique for improving attention, providing real-time feedback on brain activity in the form of visual or auditory cues, and allowing users to learn to self-regulate their cognitive processes. This study compares the effectiveness of different cues in NF training for attention enhancement through a multimodal approach. We conducted neurological (Quantitative Electroencephalography), neuropsychological (Mindfulness Attention Awareness Scale-15), and behavioral (Stroop test) assessments before and after NF training on 36 healthy participants, divided into audiovisual (G1) and visual (G2) groups. Twelve NF training sessions were conducted on alternate days, each consisting of five subsessions, with pre- and post-NF baseline electroencephalographic evaluations using power spectral density. The pre-NF baseline was used for thresholding the NF session using the beta frequency band power. Two-way analysis of variance revealed a significant long-term effect of group (G1/G2) and state (before/after NF) on the behavioral and neuropsychological assessments, with G1 showing significantly higher Mindfulness Attention Awareness Scale-15 scores, higher Stroop scores, and lower Stroop reaction times for interaction effects. Moreover, unpaired t -tests to compare voxel-wise standardized low-resolution brain electromagnetic tomography images revealed higher activity of G1 in Brodmann area 40 due to NF training. Neurological assessments show that G1 had better improvement in immediate, short-, and long-term attention. The findings of this study offer a guide for the development of NF training protocols aimed at enhancing attention effectively.

Central retinal artery occlusion (CRAO) is a serious eye condition that poses a risk to vision, resulting from the blockage of the central retinal artery. Because of the anatomical connection between the ocular artery, which derives from the internal carotid artery, and the anterior middle cerebral artery, hemodynamic alterations and sudden vision loss associated with CRAO may impact brain functionality. This study aimed to examine alterations in spontaneous neural activity among patients with CRAO by resting-state functional MRI. In addition, we selected the amplitude of low-frequency fluctuation (ALFF) and fractional amplitude of low-frequency fluctuation (fALFF) values as classification features for distinguishing CRAO from healthy controls (HCs) using a support vector machine classifier. A total of 18 patients diagnosed with CRAO and 18 HCs participated in the study. Resting-state brain function images and structural images were acquired from both groups. Aberrant changes in spontaneous brain functional activity among CRAO patients were investigated utilizing ALFF and fALFF analysis methods. Group differences in ALFF/fALFF values were assessed through a two-sample t -test. Subsequently, a machine learning classifier was developed to evaluate the clinical diagnostic potential of ALFF and fALFF values. In comparison to HCs, individuals with CRAO exhibited significantly higher ALFF values in the left cerebellum_6, vermis_7, left superior frontal gyrus, and left inferior frontal gyrus, triangular part. Conversely, the CRAO group displayed notably lower ALFF values in the left precuneus and left median cingulum gyri. Furthermore, higher fALFF values were observed in the left inferior frontal gyrus, triangular part, whereas lower fALFF values were noted in the right cerebellum_Crus2, left precuneus, right angular gyrus, left angular gyrus, right supramarginal gyrus, right superior parietal gyrus, and left precuneus. Utilizing the ALFF/fALFF values, the receiver operating characteristic curves (area under the curve) yielded 0.99 and 0.94 through machine learning analysis techniques. CRAO patients exhibit atypical neural activity in the brain, characterized by ALFF and fALFF values predominantly localized in the frontal, parietal, and cerebellar regions, which are closely linked to visual cognition and motor control impairments. Furthermore, ALFF and fALFF could serve as potential neuroimaging markers beyond the orbit among CRAO.

We aimed to study the reparative effects of orientin against spinal cord injury (SCI) in rats and explore its potential mechanisms. Sprague-Dawley rats were divided into Sham, SCI, Orientin, and SB203580 [an inhibitor of p38 mitogen-activated protein kinase (p38MAPK)] groups. In the SCI group, rats underwent Allen's beat. SCI animals in Orientin and SB203580 groups were respectively treated with 40 mg kg-1 orientin and 3 mg kg-1 SB203580 once daily. Functional recovery was evaluated based on Basso, Beattie, and Bresnahan scoring. Histopathological analysis was performed using hematoxylin-eosin and Nissl staining. Cell apoptosis was examined by TUNEL staining. The relative quantity of apoptosis-related proteins, glial fibrillary acidic protein (GFAP), neurofilament 200 (NF200), and brain derived neurotrophic factor (BDNF) was detected via western blotting. The indices related to inflammation and oxidation were measured using agent kits. The p38MAPK/inducible nitric oxide synthase (iNOS) signaling activity was detected using real-time quantitative PCR, western blotting, and immunohistochemical staining. Orientin was revealed to effectively mitigate cell apoptosis, neuroinflammation, and oxidative stress in impaired tissues. Meanwhile, orientin exerted great neuroprotective effects by abating GFAP expression, and up-regulating the expression of NF200 and BDNF, and significantly suppressed the p38MAPK/iNOS signaling. Orientin application could promote the repair of secondary SCI through attenuating oxidative stress and inflammatory response, reducing cell apoptosis and suppressing p38MAPK/iNOS signaling.

Neuromuscular junctions are innervated by motor and sympathetic nerves. The sympathetic modulation of motor innervation shows functional decline during aging, but the cellular and molecular mechanism of this change is not fully known. This study aimed to evaluate the effect of aging on sympathetic nerves and synaptic proteins at mouse neuromuscular junctions. Sympathetic nerves, presynaptic, and postsynaptic proteins of sympathetic nerves at neuromuscular junctions were visualized using immunohistochemistry, and aging-related changes were compared between adult-, aged-, and nicotinamide mononucleotide (NMN) administered aged mice. Sympathetic nerves were detected by anti-tyrosine hydroxylase antibody, and presynaptic protein vesicular monoamine transporter 2 colocalized with the sympathetic nerves. These two signals surrounded motor nerve terminals and acetylcholine receptor clusters. Postsynaptic neurotransmitter receptor β2-adrenergic receptors colocalized with motor nerve terminals and resided in reduced density at extrasynaptic sarcolemma. The signal intensity of the sympathetic nerve marker did not show a significant difference at neuromuscular junctions between 8.5-month-old adult mice and 25-month-old aged mice. However, the signal intensity of vesicular monoamine transporter 2 and β2-adrenergic receptors showed age-related decline at neuromuscular junctions. Interestingly, both age-related declines reverted to the adult level after 1 month of oral administration of NMN by drinking water. In contrast, NMN administration did not alter the expression level of sympathetic marker tyrosine hydroxylase at neuromuscular junctions. The results suggest a functional decline of sympathetic nerves at aged neuromuscular junctions due to decreases in presynaptic and postsynaptic proteins, which can be reverted to the adult level by NMN administration.

Thyroid-associated ophthalmopathy (TAO) is a significant autoimmune eye disease known for causing exophthalmos and substantial optic nerve damage. Prior investigations have solely focused on static functional MRI (fMRI) scans of the brain in TAO patients, neglecting the assessment of temporal variations in local brain activity. This study aimed to characterize alterations in dynamic regional homogeneity (dReHo) in TAO patients and differentiate between TAO patients and healthy controls using support vector machine (SVM) classification. Thirty-two patients with TAO and 32 healthy controls underwent resting-state fMRI scans. We calculated dReHo using sliding-window methods to evaluate changes in regional brain activity and compared these findings between the two groups. Subsequently, we employed SVM, a machine learning algorithm, to investigate the potential use of dReHo maps as diagnostic markers for TAO. Compared to healthy controls, individuals with active TAO demonstrated significantly higher dReHo values in the right angular gyrus, left precuneus, right inferior parietal as well as the left superior parietal gyrus. The SVM model demonstrated an accuracy ranging from 65.62 to 68.75% in distinguishing between TAO patients and healthy controls based on dReHo variability in these identified brain regions, with an area under the curve of 0.70 to 0.76. TAO patients showed increased dReHo in default mode network-related brain regions. The accuracy of classifying TAO patients and healthy controls based on dReHo was notably high. These results offer new insights for investigating the pathogenesis and clinical diagnostic classification of individuals with TAO.