Neuroscience Letters最新文献

Glyphosate (Gly) is the active ingredient of several widely used herbicide formulations. Studies on Gly and glyphosate-based herbicide (GBH) exposure in different experimental models have suggested that the nervous system represented a key target for its toxicity, especially the prefrontal cortex (PFC). However, it is still unknown whether exposure to GBH affects higher brain functions dependent on PFC circuitry. The present work aimed to examine the effects of subtoxic doses of GBH on social cognition and cognitive flexibility as two functions belonging to higher brain function in mice. To do so, adult male mice were exposed daily to GBH by gavage at doses of 250 or 500 mg/kg for a sub-chronic period lasting 6 weeks. Then, mice were subjected to behavioral testing using the three-chamber and the Barnes maze paradigms. Our results indicate that GBH did not affect sociability. However, we found that GBH affects social cognition expressed by a lower discrimination index in the three-chamber test. Moreover, spatial memories evaluated during the probe trial, and cognitive flexibility evaluated during the reversal probe, were affected in mice exposed to GBH. Based on these results, exposure to subtoxic doses of GBH led to neurobehavioral alterations affecting the integrity of social cognition and cognitive flexibility functions. Finally, these data urge a thorough investigation of the cellular and molecular mechanisms underlying these alterations.

Rho-associated protein kinase-2 (ROCK2) is a critical player in many cellular processes and was incriminated in cardiovascular and neurological disorders. Recent evidence has shown that non-selective pharmacological blockage of ROCKs ameliorates behavioral alterations in a mouse model of 16p11.2 haploinsufficiency. We had revealed that 16p11.2-deficient mice also display cerebrovascular abnormalities, including endothelial dysfunction. To investigate whether genetic blockage of ROCK2 also exerts beneficial effects on cognition and angiogenesis, we generated mice with both 16p11.2 and Rock2 haploinsufficiency (16p11.2^df/+;Rock2^+/−). We find that Rock2 heterozygosity on a 16p11.2^df/+ background significantly improved recognition memory. Furthermore, brain endothelial cells from 16p11.2^df/+;Rock2^+/− mice display improved angiogenic capacity compared to cells from 16p11.2^df/+ littermates. Overall, this study implicates Rock2 gene as a modulator of 16p11.2-associated alterations, highlighting its potential as a target for treatment of autism spectrum disorders.

Neurological or neurodevelopmental disorders, such as Parkinson’s disease and dyslexia, can impair rhythm perception and production. Deficits in rhythm are associated with poor performance in language, attention, and working memory tasks. Research indicates that retraining rhythmic skills may enhance these related cognitive functions. In this context, using tactile aids for rhythm training emerges as a promising approach for children who do not fully benefit from conventional audiovisual rhythm games. This is because tactile aids can compensate for sensory deficiencies and facilitate more extensive brain activation. In our study, we employed functional near-infrared spectroscopy (fNIRS) to assess the impact of tactile aids on brain cortical activation during rhythmic training in children aged 6–12 years (N = 25). We also measured the participants’ spontaneous motor rhythms. The findings indicate that tactile stimulation significantly improves performance in synchronized rhythm tasks compared to audiovisual stimulation alone, particularly enhancing activation in brain regions associated with speech training such as the prefrontal cortex, motor cortex, and temporal areas. These results not only support the application of rhythm training in speech rehabilitation, but also highlight the potential of tactile aids as an effective multisensory learning strategy.

The mechanism by which postural threat induced by standing at a high height causes a decrease in the amplitude and an increase in the frequency of postural sway might involve voluntary control (VC) to avoid swaying, rather than conscious balance processing, in which postural threat directs conscious balance processing. This study aimed to clarify the differences between VC and conscious balance processing during quiet standing. Twenty-seven healthy young adults were instructed to stand with their feet placed together and keep their eyes open. The standing task was performed under three standing conditions: relaxed, VC, and high-conscious movement processing (high-CMP). The center of pressure in the anteroposterior (AP) and mediolateral (ML) directions was measured using a stabilometer to assess differences in postural control. The results indicated that the mean power frequency (MPF) ML and high frequency (HF) ML were higher in the VC condition than in the high-CMP condition. In the VC and high-CMP conditions, compared with the relaxed condition, MPF AP was higher, whereas the root mean square AP and low frequency AP were lower. These results show that the sway amplitude is lower, and the frequency is higher in both the VC and high-CMP conditions compared with those in the relaxed condition; however, the frequency is higher in the VC condition than in the high-CMP condition, suggesting that the VC condition is similar to postural control under the postural threat condition.

Purpose

Sex differences play a crucial role in understanding vulnerability to opioid addiction, yet there have been limited preclinical investigations of this effect during the transition from adolescence to adulthood. The present study compared the behaviors of male and female rodents in response to fentanyl treatment and targeted molecular correlates in the striatum and medial prefrontal cortex.

Materials and methods

Thirty adolescent C57BL/6J mice underwent a 1-week fentanyl treatment with an escalating dose. In addition to evaluating locomotor activity and anxiety-related parameters, we also assessed naloxone-induced fentanyl acute withdrawal jumps. We employed real-time quantitative PCR (qPCR) to assess overall gene expression of dopaminergic receptors (Drd1, Drd2, Drd4 and Drd5) and the μ-opioid receptor Oprm1. The levels of epigenetic base modifications including 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) were assessed on CpG islands of relevant genes.

Results

Females had higher locomotor activity than males after chronic fentanyl treatment, and they exhibited higher fentanyl withdrawal jumping behavior induced by naloxone. Females also presented lower Drd4 gene expression and DNA methylation (5mC + 5hmC) in the striatum. We found that locomotor activity and fentanyl withdrawal jumps were negatively correlated with Drd4 methylation and gene expression in the striatum, respectively.

Conclusions

The findings suggested that female mice displayed heightened sensitivity to the effects of fentanyl treatment during the transition from adolescence to adulthood. This effect may be associated with molecular alterations related to the Drd4 gene.

The efficacy of vitamin C in age-related hearing loss, i.e., presbycusis, remains debatable. On a separate note, inflammation induced by the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is involved in the progression of presbycusis. In this study, we investigated the effect of vitamin C on male C57BL/6 mice’s presbycusis and NLRP3 inflammasome. The results showed that vitamin C treatment improved hearing, reduced the production of inflammatory factors, inhibited NLRP3 inflammasome activation, and decreased cytosolic mitochondrial DNA (mtDNA) in the C57BL/6 mouse cochlea, inferior colliculus, and auditory cortex. According to this study, vitamin C protects auditory function in male C57BL/6 presbycusis mice through reducing mtDNA release, inhibiting the NLRP3 inflammasome activation in the auditory pathway. Our study provides a theoretical basis for applying vitamin C to treat presbycusis.

Introduction

Following amputation, peripheral nerves lack distal targets for regeneration, often resulting in symptomatic neuromas and debilitating neuropathic pain. Animal models can establish a practical method for symptomatic neuroma formation for better understanding of neuropathic pain pathophysiology through behavioral and histological assessments. We created a clinically translatable animal model of symptomatic neuroma to mimic neuropathic pain in patients and assess sexual differences in pain behaviors.

Methods

Twenty-two male and female rats were randomly assigned to one of two experimental groups: (1) neuroma surgery, or (2) sham surgery. For the neuroma experimental group, the tibial nerve was transected in the thigh, and the proximal segment was placed under the skin for mechanical testing at the site of neuroma. For the sham surgery, rats underwent tibial nerve isolation without transection. Behavioral testing consisted of neuroma-site pain, mechanical allodynia, cold allodynia, and thermal hyperalgesia at baseline, and then weekly over 8 weeks.

Results

Male and female neuroma rats demonstrated significantly higher neuroma-site pain response compared to sham groups starting at weeks 3 and 4, indicating symptomatic neuroma formation. Weekly assessment of mechanical and cold allodynia among neuroma groups showed a significant difference in pain behavior compared to sham groups (p < 0.001). Overall, males and females did not display significant differences in their pain responses. Histology revealed a characteristic neuroma bulb at week 8, including disorganized axons, fibrotic tissue, Schwann cell displacement, and immune cell infiltration.

Conclusion

This novel animal model is a useful tool to investigate underlying mechanisms of neuroma formation and neuropathic pain.

Reciprocal connections between the thalamus and the cortex are one of the most characteristic features of forebrain organization in mammals. To date, this circuit has been documented only in turtles. However, reptiles, including turtles, have an additional path from the dorsal thalamus to the telencephalon. This terminates in a pallial structure known as the dorsal ventricular ridge. Yet, no reciprocal connection from the dorsal ventricular ridge to thalamic nuclei has been uncovered. Since axons from the thalamus pass through the basal nuclei on route to the dorsal ventricular ridge, the basal nuclei might be a source of reciprocal connections. Accordingly, the location and distribution of neurons after retrograde tracer placement into the dorsal thalamus were examined. Retrogradely labeled neurons in the basal nuclei were indeed found. One possibility to explain this observation is that connections with the dorsal ventricular ridge are present during development but later pruned during embryogenesis.

Background

Perceptible galvanic vestibular stimulation (GVS) causes nystagmus and postural sway deterioration. Conversely, imperceptible GVS improves postural stability, suggesting the presence of stochastic resonance.

Research question

Similar to GVS, strong magnetic vestibular stimulation of 7 T induces nystagmus and increases body sway. Thus, a relatively small magnetic stimulation may improve postural stability. In this study, we measured the effect of a relatively small magnetic field on postural sway.

Methods

Posturography was performed in eight healthy participants using a stabilometer with foam rubber on board. The center of pressure (COP) trajectories were recorded in both the anterior–posterior and medial–lateral directions for 60 s with the eye closed. Neodymium magnets (0.4 T) or aluminum disks of similar size (0 T) were placed bilaterally over the mastoid processes.

Results

Both the trajectory length and envelopment area of the COP movement with 0.4 T were significantly smaller than those with 0 T.

Significance

The relatively smaller magnetic vestibular stimulation decreased postural sway. This method may be useful for improving the vestibular function and related reflexes.

Shikonin is an active naphthoquinone with antioxidative, anti-inflammatory, and anticancer properties. In this study, we investigated the effects of shikonin on depressive- and anxiety-like behaviors in lipopolysaccharide- (LPS-) induced depression and chronic unpredictable mild stress (CUMS) rat models and explored the potential mechanism. First, a 14-day intraperitoneal administration of shikonin (10 mg/kg) significantly decreased immobility time in forced swimming test (FST) and increased open arm entries in elevated plus maze (EPM) test, without affecting line crossings in open field test (OFT), indicating that shikonin has anti-depressant- and anxiolytic-like effects. Second, chronic shikonin administration (10 mg/kg) reversed depressive- and anxiety-like behaviors in LPS-induced and CUMS depression models, as shown in the sucrose preference test (SPT), FST, EPM, and novel object recognition test (NORT). Finally, shikonin significantly reduced the levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) in hippocampus, indicating that the anti-depressant- and anxiolytic-like effects of shikonin are related to the reduction of neuroinflammation in hippocampus. These findings suggest that shikonin exerts anti-depressant- and anxiolytic-like effects via an anti-inflammatory mechanism of shikonin in the hippocampus.