Neuroreport最新文献

To date, most studies on autism spectrum disorder (ASD) have focused on specific age ranges, while the mechanisms underlying the entire developmental process of autism patients remain unclear. The aim of this study was to investigate the alterations in brain function in autistic individuals at different developmental stages by resting-state functional MRI (rs-fMRI). We obtained rs-fMRI data from 173 ASD and 178 typical development (TD) individuals in Autism Brain Imaging Data Exchange, spanning child, adolescent, and adult groups. We characterized local brain activity using the amplitude of low-frequency fluctuations (ALFFs), regional homogeneity (ReHo), dynamic ALFF (dALFF), and dynamic ReHo (dReHo) metrics. Pearson correlation analyses were conducted on relationships between Autism Diagnostic Observation Schedule scores and activity measures in abnormal brain regions. We found abnormal ALFF values in the medial and lateral orbitofrontal gyrus and right insula cortex with ASD compared with the TD group. In addition, compared with adolescents with ASD, we found that adults with ASD exhibited an increase in dReHo values in the posterior lateral frontal lobe. We also found that changes in ALFF were associated with the severity of autism. We found abnormal activity in multiple brain regions in individuals with autism and correlated it with clinical characteristics. Our results may provide some help for further exploring the age-related neurobiological mechanisms of ASD patients.

Spinal cord injury (SCI) causes interruption of external information input from the spinal cord to the cerebellum. We here investigated the effect of SCI on mouse cerebellar climbing fiber-Purkinje cell (CF-PC) synaptic transmission. The SCI was caused at T10 using 6-week-old ICR mice. Mice recovered 4 weeks after surgery, the spontaneous complex spike (CS) activity of PC was recorded using cell-attached recording and whole-cell recording method in urethane-anesthetized mice cerebellar Crus II. The CF-PC excitatory postsynaptic currents (EPSCs) were evoked by paired electrical stimulation of CF in cerebellar slices to evaluate the changes of CF-PC synaptic transmission and paired-pulse ratio (PPR). The results showed that the number of spikelets, duration of spontaneous CS, and pause of simple spike firing were significantly increased in SCI than that in sham group. Application of a nonselective corticotropin-releasing factor receptor (CRF-R) antagonist significantly decreased spontaneous CS activity in SCI group but not in sham group. The enhanced CS activity in SCI mice was significantly decreased by a selective CRF-R2 antagonist but not a specific CRF-R1 antagonist. The amplitude of CF-PC EPSC1 was large accompanied by a lower PPR in SCI group than that in sham group. Blockade of CRF-R2 antagonist significantly decreased the amplitude of EPSC1 and increased PPR in SCI group. SCI induces enhancement of the spontaneous CS activity and CF-PC synaptic transmission via CRF-R2 in mouse cerebellar cortex, which suggests that remodeling of CF-PC synaptic transmission occurred in cerebellar cortex after SCI.

This study aims to investigate how the level of semantic relevance influences the effects of test on associative memory through bottom-up cognitive processes. This study manipulated the levels of semantic relevancy using synonym and nonsynonym pairs in a three-phase testing effect paradigm (an initial encoding phase, a cued-recall test as retrieval practice, and a final test phase) to explore the effects of testing effect and semantic relevancy on associative recognition by bottom-up processes using the event-related potential (ERP). The behavioral results suggested that the test practice (relative to the restudy) significantly facilitated memory retrieval in high semantic relevancy pairs during the final test phase. The ERP results showed that the testing effect tended toward right laterality over time in the retrieval practice phase. Moreover, test practice (relative to the restudy) significantly enhanced FN400 for high semantic relevancy and intact pairs and significantly enhanced FN400 and late positive complex for high semantic relevancy and rearranged pairs in the final test phase. These results suggest that the test practice provided a greater boost in memory encoding and retrieval for high semantic relevancy items. Specifically, the effects of test on associative memory is modulated by the level of semantic relevancy.

Videofluoroscopic swallow study methodology in mice has recently been established; however, details of developmental and age-related changes remain unclear. This study aimed to reveal the changes in swallowing associated with the entire lifespan of mice using the videofluoroscopic swallow study methodology. We tested six age groups of male C57BL/6J mice (4, 8, 16, 54, 77, and 104 weeks old; n = 5 for each group, respectively). The videofluoroscopic swallow study analyzed the bolus area, pharyngeal transit time, interswallow interval, lick-swallow ratio, and lick rate. Significant age differences were found in the bolus area and lick rate. The bolus area increased significantly as the mice grew older. There was a significant increase in the lick rate from 4 to 8 weeks (P < 0.001) and then a significant decrease from 8 to 104 weeks (P < 0.01). No significant difference was observed between the various stages in the lick-swallow ratio, interswallow interval, or pharyngeal transit time. There was a significant positive correlation between the body weight and bolus area. This study revealed the detailed changes in swallowing at each life stage from swallowing maturation to old age in the mice. Our research may serve as a guide for future studies on swallowing in humans.

The present study aimed to evaluate the association between concentrations of the metabolites gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx), which have predominantly inhibitory and excitatory effects on neural function, respectively, in adults with tinnitus and hearing loss, those with only hearing loss, and controls with neither condition. Metabolite concentrations in all three participant groups were assessed via magnetic resonance spectroscopic imaging in auditory and fronto-parietal regions. The concentration of a third metabolite, creatine (Cre) was also acquired. Ratios of GABA/Cre, Glx/Cre, and Glx/GABA were compared across six manually delineated regions of interest (ROIs). Neither GABA/Cre nor Glx/Cre showed significant group differences in any of the six ROIs. For the Glx/GABA ratio, group-level differences were seen only in the right auditory cortex, where the control group had a significantly larger ratio than the group with tinnitus and hearing loss. While results largely did not replicate previous human work in this area, we cannot exclude the possibility of a neurochemical mechanism underlying any causal relationship between hearing loss and tinnitus, particularly given the finding of altered balance in excitatory/inhibitory metabolites in the right auditory cortex. In the context of previous work, the right auditory cortex is highlighted as a particular region of interest for further investigation. Methodological differences in human studies and inconsistent findings in animal studies have thus far impeded the field's ability to gain direct insight into the relationship between tinnitus and hearing loss, and so we make some suggestions to help design future studies.

Cannabinoid type 1 receptors (CB1Rs) play important roles in regulating neurotransmitter release, synaptic plasticity, cell differentiation, and survival. CB1R is coupled via pertussis toxin (PTX)-sensitive Gαi/o proteins to the activation of extracellular regulated kinase (ERK) signaling. However, there are multiple Gαi/o isoforms, and it is unknown which of these isoforms is responsible for CB1R-induced phosphorylation of ERK. The purpose of this study was to determine which Gαi/o isoform(s) couple CB1R to ERK phosphorylation. HEK293 cells stably expressing the mouse CB1R (CB1R-HEK cells) were transfected with either pcDNA3.1 or pcDNA3.1 encoding PTX-insensitive mutants of Gαo, Gαi1, Gαi2, or Gαi3. PTX was used to inactivate endogenous Gαi/o isoforms before cells were treated with vehicle, delta-9-tetrahydrocannabinol (∆9-THC), or CP55940 and ERK phosphorylation was measured by western blotting. CP55940 induced robust phosphorylation of ERK in cells transfected with vector alone. This effect was completely abolished by PTX treatment. CP55940-induced ERK phosphorylation was rescued by expression of PTX-insensitive forms of Gαo, Gαi1, Gαi2, or Gαi3, indicating that the CB1 receptor can couple to ERK phosphorylation through each of these Gαi/o isoforms. Consistent with its actions as a partial agonist, ∆9-THC induced nominal (two to four-fold) increases in ERK phosphorylation that did not reach statistical significance except in cells transfected with PTX-insensitive Gαi3. These data demonstrate that CB1R can couple to ERK phosphorylation through Gαo, Gαi1, Gαi2, or Gαi3 when stimulated with CP55940 (full agonist). However, ∆9-THC (partial agonist)-induced ERK activation might require high levels of Gαi3 expression.

Exercise (Ex) and environmental enrichment (EE) as the nondrug solutions have positive effects on cognitive behaviors and also increase the ability to cope with anxiety, fear, and stress. In this research, we decided to investigate the simultaneous effect of Ex and EE on anxiety-like behaviors and hippocampal neurogenesis markers in healthy rats. A total of 40 male Wistar rats were divided into four treatment groups: control, EE, Ex, and EE + Ex. Animals in EE groups were housed in large cages (50 × 50 × 50 cm) equipped with toys and objects of different shapes for 3 weeks. Ex-animals were forced to run on a treadmill once a day for 3 consecutive weeks. Open field (OF) and elevated plus maze (EPM) tests were used to evaluate anxiety behaviors. The hippocampal expression of early neurogenesis markers, doublecortin, and sex determining region Y-box 2, were measured using real-time-PCR. Ex and EE animals separately did not show any significant performance in reducing anxiety levels, neither in EPM nor in OF compared with the control group. When animals were treated with EE and Ex simultaneously, they showed significantly reduced anxiety in both EPM and OF tests compared with the control as well as Ex and EE groups separately. Both treatments in combination were also more effective than individual groups in increasing the neurogenesis molecular markers within the hippocampus. This study proposes that Ex in combination with cognitive engagement is more efficient in alleviating anxiety responses and that can develop a nonpharmacological and multidomain policy that may prevent or delay psychophysiological symptoms.

Embodied cognition is known to play a role in verbal semantic processing. However, its involvement in nonverbal semantic elements, such as arrows, is less understood. Two spatial recognition tasks, specifically arrow-orientation recognition and arrow-position recognition, were employed using directional arrows in various spatial arrangements as visual stimuli. Stimuli were categorized into congruent (where orientation and position align), incongruent 1 (where orientation and position are directly opposing), and incongruent 2 (where orientation and position are unrelated) groups for both tasks. To investigate neural processes, event-related potentials (ERPs) were recorded and analyzed during task performance. Additionally, standardized low-resolution electromagnetic tomography (sLORETA) was utilized to examine brain electrical activity during ERP intervals. The analysis revealed significant ERP component differences between congruent and incongruent conditions across both spatial tasks, highlighting a Stroop-like interference effect. Notably, the arrow-orientation task showed marked enhancements in P3 and N400 components, as well as heightened brain activity in the frontal lobe, anterior cingulate cortex, and insula, compared with the arrow-position task. These findings suggest that embodied cognition is involved in both spatial arrow recognition tasks. The unique role of embodied cognition in these contexts is primarily reflected in the modulation of the P3-N400 complex, indicating differentiated cognitive processing.

Anti-cancer agent paclitaxel induces cognitive impairment. Paclitaxel can induce limited neuron apoptosis and wide scope of neuroinflammation, but its precise mechanisms remain unclear. In this study, we determined paclitaxel causes necroptosis, a programmed cell death, via activation of the RIPK1-RIPK3-MLKL signaling pathway in hippocampal neurons (HT22 cells). Flow cytometric analysis, propidium iodide staining, and western blotting techniques were used to evaluate paclitaxel-induced necroptosis. Cell viability was determined using the Cell Counting Kit-8 assay, and the Ca2+ levels were measured using a Fluo-4 AM fluorescent probe. The number of cells positive for both annexin V and propidium iodide staining was significantly higher in paclitaxel-treated than vehicle-treated HT22 cells. Additionally, the nuclei of paclitaxel-treated cells exhibited more diffused necrotic propidium iodide staining than the vehicle-treated cells. The expression of necroptosis-associated proteins, including receptor-interacting protein kinase (RIPK)1, RIPK3, mixed lineage kinase domain-like protein (MLKL), and phosphorylated (p)-MLKL, were increased following paclitaxel treatment. Treating HT22 cells with necrostatin-1, a specific inhibitor for RIPK1, effectively decreased paclitaxel-induced necroptosis through lowering intracellular Ca2+ overload. In addition, administration of necrostatin-1 to paclitaxel-treated mice rescued cognitive impairments, as assessed by novel object recognition and Morris water maze tests. Necrostatin-1 also reduced the increases in necroptosis-associated protein levels of RIPK1, RIPK3, MLKL, and p-MLKL in hippocampal tissue of paclitaxel-treated mice. Paclitaxel induces cognitive deficits through RIPK1-mediated necroptosis. The inhibition of necroptosis may be a potential therapeutic approach to reduce paclitaxel-induced cognitive deficits.

To investigate the effects of chronic exposure to the cardiotonic steroid digoxin on locomotor activity, anxiety, and brain tissue monoamine content in Zebrafish. In total 24 adult (3-5 months) wild-type experimentally naïve zebrafish (50 : 50 ratio of females to males) were housed in 4-L tanks, in groups of six animals per tank. Two μM Digoxin was maintained in half of the tanks for 7 days. The 'Novel tank test' was performed on day 7 and the animals were euthanized. Concentrations of dopamine, serotonin, and their metabolites were then quantified in brain tissue using HPLC-ED. Seven-day exposure to 2 μM water solution of digoxin caused robust hyperlocomotion and reduced anxiety-like behavior in adult zebrafish in the 'Novel tank test'. The treatment also evoked pronounced neurochemical responses in zebrafish, including increased whole-brain 3-methoxytyramine, reduced norepinephrine and serotonin, and unaltered dopamine, homovanillic acid or 5-hydroxyindoleacetic acid levels. Deficits in monoaminergic (dopaminergic, serotonergic, and noradrenergic) neurotransmission are a key pathogenetic factor for multiple neuropsychiatric and neurodegenerative diseases. Commonly used clinically to treat cardiac conditions, cardiotonic steroids can affect dopaminergic neurotransmission. Chronic exposure to digoxin evokes hyperactivity-like behavior accompanied by altered monoamine neurotransmission in zebrafish, which may be relevant to understanding the central nervous system side effects of cardiotonic steroids.