Neuroreport最新文献

Objective: Studying the effect of deep brain stimulation (DBS) in the lateral hypothalamic area (LHA) in young and aging rats regarding memory changes, hippocampal neuronal dystrophy, and neurofilament expression.

Methods: Thirty-six male Sprague-Dawley rats were divided into two main groups: adult young ( n  = 18, 8 weeks old) and aged ( n  = 18, 24 months old). Each main group was further subdivided into three equal subgroups ( n  = 6) including control, sham, and DBS. DBS of LHA was conducted using high-frequency electric currents (130 Hz) for 1.5 h with 5-min breaks every 30 min for five consecutive days. Assessment of working memory was done using passive avoidance test (PAT). Then, the brain was dissected and hippocampal neuronal dystrophic damage was assessed as well as immunohistochemical examination of neurofilaments (NF68, NF200) expression.

Results: Aging rats had progressive hippocampal neuronal degeneration and downregulation of heavy and light chain neurofilaments, that was associated with progressive decline in working memory. Nevertheless, activation of DBS in the LHA enhanced memory function as it increased latency to entry in PAT ( P  < 0.001) compared to old normal and sham groups. Dystrophic damage score significantly decreased with DBS ( P  < 0.001) in the hippocampal CA1, CA3, and dentate gyrus regions. Moreover, DBS upregulated hippocampal NF68, NF200 expression ( P  < 0.001) in both young and old rats. We also found a significant positive correlation between working memory and NFs expression and a negative correlation between dystrophic damage score and NFs expression.

Conclusions: DBS in the LHA may have a neuroprotective effect in aging rats as it enhanced the working memory and decreased hippocampal neuronal dystrophy. This protective effect may be caused by the upregulation of neurofilaments.

Low back pain (LBP) is a prevalent pain condition whose persistence can lead to changes in the brain regions responsible for sensory, cognitive, attentional, and emotional processing. Previous neuroimaging studies have identified various structural and functional abnormalities in patients with LBP; however, how the static and dynamic large-scale functional network connectivity (FNC) of the brain is affected in these patients remains unclear. Forty-one patients with chronic low back pain (cLBP) and 42 healthy controls underwent resting-state functional MRI scanning. The independent component analysis method was employed to extract the resting-state networks. Subsequently, we calculate and compare between groups for static intra- and inter-network functional connectivity. In addition, we investigated the differences between dynamic functional network connectivity and dynamic temporal metrics between cLBP patients and healthy controls. Finally, we tried to distinguish cLBP patients from healthy controls by support vector machine method. The results showed that significant reductions in functional connectivity within the network were found within the DMN,DAN, and ECN in cLBP patients. Significant between-group differences were also found in static FNC and in each state of dynamic FNC. In addition, in terms of dynamic temporal metrics, fraction time and mean dwell time were significantly altered in cLBP patients. In conclusion, our study suggests the existence of static and dynamic large-scale brain network alterations in patients with cLBP. The findings provide insights into the neural mechanisms underlying various brain function abnormalities and altered pain experiences in patients with cLBP.

From a vestibular perspective, it is remarkable that dancers are often performing challenging tasks such as pirouettes, and yet manage to do so without falling. Some have suggested that dancers' resistance to vertigo may be explained by a generalized suppression of vestibular signaling. Here, we aimed to test this hypothesis by examining the impact of galvanic vestibular stimulation (GVS) on postural control in dancers. A total of 38 participants were recruited for this study and were divided into two groups: 19 dancers and 19 healthy controls. Postural control was assessed at baseline and during GVS. As expected, dancers exhibited better postural control, as assessed by a decrease in sway area, when compared to the control group in the baseline condition. However, contrary to expectations, dancers did not differ from controls during GVS. This confirms that dancers' resistance to vertigo cannot be explained by a generalized suppression of vestibular signaling. Rather, dancers may have developed a more accurate body representation due to top-down modulation of subcortical neuronal networks and may only be able to modify vestibular input during active movement.

The long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) might protect against cerebral ischemic injury. This study explored MALAT1's function in ischemic stroke and whether it acts through the caveolin-1/vascular endothelial growth factor (VEGF) pathway. A mouse model of middle cerebral artery occlusion/reperfusion (MCAO/R) and a human brain microvascular endothelial cell (HBMEC) model of oxygen-glucose deprivation/reoxygenation (OGD/R) were established. Lentiviral vectors for MALAT1 knockdown, caveolin-1 knockdown, and MALAT1 overexpression were used for gene regulation studies. Neurological deficits, endothelial cell proliferation, cell apoptosis, cell viability, in vitro angiogenesis, cell migration, and the expression of related gene and protein were evaluated using the Zea Longa five-point scale, VEGF receptor 2/CD34 double immunofluorescence, TdT-mediated dUTP nick end labeling staining, cell counting kit-8 assay, tube formation assay, transwell assay, quantitative real time PCR, and western blot. In mouse MCAO/R model and HBMEC OGD/R model, the expression levels of MALAT1, caveolin-1, and VEGF were significantly upregulated compared to the control group. In vivo, downregulation of MALAT1 expression exacerbated cerebral ischemic injury as manifested by severe neurological deficits, larger infarct volume, increased apoptosis, decreased numbers of VEGF receptor 2+/CD34+ endothelial progenitor cells, increased cell apoptosis, and the downregulation of caveolin-1 and VEGF. Conversely, overexpression of MALAT1 partially reversed the inhibition of cell migration and tubule formation by caveolin-1 gene downregulation, and restored in the expression of caveolin-1 and VEGF. MALAT1 promotes angiogenesis after cerebral ischemic injury, likely in part via the caveolin-1/VEGF pathway. Thus, MALAT1 may serve as a potential therapeutic target for ischemic stroke.

Explore the correlation between basal ganglia nuclei and cortical gray matter volume changes in tremor-dominant and postural instability-gait difficulty (PIGD) Parkinson's disease subtypes for Parkinson's disease diagnosis and individualized treatment. High-resolution 3D-T1WI MRI data from 35 tremor-dominant and 30 PIGD patientsand 35 healthy controls were analyzed. Voxel-based morphometry identified gray matter volume differences. Automated basal ganglia segmentation quantified subcortical volumes, followed by multivariate analysis of covariance and Spearman correlation analyses. Compared with healthy control, patients with PIGD exhibited severe gray matter loss (P < 0.0001), while tremor-dominant showed nonsignificant reductions. Subcortically, different basal ganglia volumes were atrophied in the tremor-dominant and PIGD groups compared with the healthy control (P < 0.05). PIGD demonstrated greater left putamen atrophy than tremor-dominant (P < 0.05). Spearman correlation analysis revealed that the volume of the right globus pallidus was positively correlated with that of the left medial and lateral cingulate gyrus in patients with tremor-dominant (r = 0.35, P = 0.04); and between the left globus pallidus volume and the right superior temporal gyrus volume in patients with PIGD (r = 0.47, P = 0.01). Compared with the tremor-dominant subtype, the PIGD subtype exhibits more severe GM atrophy, with different basal ganglia volume changes across subtypes. These altered anatomical features and the correlation between degeneration of the basal ganglia region and cortical gray matter changes may provide insights into the differential functional changes in patients with different motor subtypes and help to elucidate the underlying pathologic mechanisms.

We investigated the relationship between aperiodic electroencephalography (EEG) activity and code conflict, hypothesizing that the former might serve as an indicator of the latter. We analyzed EEG and behavioral outcomes of a sample performing the event file task, which assesses code conflict in co-occurring or temporally overlapping stimulus and response features. To quantify aperiodic activity, we employed the fitting oscillations & one-over-f algorithm. The behavioral results revealed a typical partial-repetition cost effect, indicating that performance is impaired if the stimulus repeats while the response alternates, or vice versa. This suggests that the previously combined shape and response were stored in an event file and retrieved when any one of these components was repeated. Notably, this effect was also evident in the aperiodic exponent, which was lower for partial repetitions than for full repetitions or alternations, implying increased cortical noise, a higher excitatory E/I ratio, and noisier decision-making processes. The scalp distribution of this effect aligns with its sensorimotor characteristics. Thus, we interpret these findings as promising preliminary evidence that the aperiodic exponent may serve as a valuable neural marker of code conflict.

Poststroke depression (PSD) affects approximately one-third of stroke survivors, contributing to poor outcomes and elevated mortality. This study aimed to investigate the therapeutic effects of hydrogen sulfide (H2S), administered as sodium hydrosulfide (NaHS), on PSD-induced inflammation, with a focus on the modulation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) pathway and the enhancement of endoplasmic reticulum (ER) autophagy in microglial cells. An in-vivo rat model was established to evaluate the effects of NaHS on depression-like behaviors and inflammation. Mechanistic studies were conducted in vitro using BV2 microglia subjected to oxygen-glucose deprivation (OGD) and corticosterone. Key inflammatory markers, cGAS-STING pathway activity, and ER-autophagy-related proteins were analyzed using quantitative reverse transcription PCR, Western blotting, ELISA, transmission electron microscopy, and immunofluorescence staining. Depression-like behaviors in rats were assessed using the forced swimming and tail suspension tests. H2S treatment ameliorated depression-like symptoms, mitigated hippocampal damage, and reduced pro-inflammatory markers, including NOD-like receptor protein 3, interleukin-1β (IL-1β), and IL-18 by inhibiting the cGAS-STING pathway. Furthermore, H2S significantly upregulated autophagy-related proteins (LC3, Beclin-1, and FAM134B) and autophagic vesicles, indicating enhanced ER autophagy. Notably, silencing FAM134B reversed the inhibitory effects of H2S on the cGAS-STING pathway, underscoring the pivotal role of ER autophagy in H2S-mediated neuroprotection. These findings demonstrate that H2S mitigates PSD-induced microglial inflammation and depression-like behaviors by inhibiting the cGAS-STING pathway and promoting ER autophagy, suggesting its potential as a therapeutic strategy for PSD. Further investigation into H2S and autophagy-related pathways could reveal novel therapeutic avenues for neuroinflammatory conditions.

To investigate the effects of resveratrol (RES) on cognitive function and its modulation of the NRF2/HO-1 signaling pathway in a rodent model of postoperative cognitive dysfunction (POCD). A POCD model was established in aged Sprague-Dawley rats using sevoflurane anesthesia and laparotomy. Rats were divided into four groups: control, POCD, RES, and POCD + RES. Cognitive performance was assessed using the Morris water maze. Hippocampal tissues were analyzed for neuronal condition using hematoxylin and eosin and Nissl staining. The expression levels of inflammatory cytokines and oxidative stress markers were quantified by enzyme-linked immunosorbent assay. The messenger RNA and protein levels of NRF2, KEAP1, HO-1, and SOD2 were measured using real-time quantitative polymerase chain reaction and western blotting. RES treatment improved cognitive function, as evidenced by reduced escape latency and increased platform crossings in the Morris water maze. Histopathological analysis showed restoration of hippocampal structure and increased neuronal viability. RES significantly reduced proinflammatory cytokines interleukin (IL)-1 and IL-6 while increasing IL-10 levels. In addition, RES activated the NRF2/HO-1 pathway by upregulating NRF2, HO-1, and SOD2 expression while downregulating KEAP1. RES mitigates cognitive deficits in POCD by reducing neuroinflammation and oxidative stress through activation of the NRF2/HO-1 signaling pathway. These findings suggest RES is a potential therapeutic candidate for the treatment of POCD in elderly patients.

Traumatic brain injury (TBI) is often accompanied by secondary brain injury (SBI), with neuroinflammation being a core mechanism of SBI. Pyroptosis is a key driver of neuroinflammatory responses, and inhibiting pyroptosis can reduce neuroinflammation after TBI and promote tissue and functional recovery. The activation of the NLRP3 inflammasome mediates the classical pyroptosis pathway, and ticagrelor can inhibit NLRP3 inflammasome activation. This study aimed to investigate the differences in pyroptosis inhibition induced by TBI with different doses of ticagrelor by targeting the activation of the NLRP3 inflammasome. Mice were randomly divided into four groups: sham, TBI, 50 mg/kg ticagrelor treatment, and 150 mg/kg ticagrelor treatment. After 24 h of treatment, brain tissue surrounding the injury was collected for immunoblot detection of pyroptosis-related protein expression and ELISA detection of inflammatory cytokine release. On day 3 after treatment, BBB permeability and brain edema were assessed by injection of Evans blue and measurement of brain tissue water content. On day 7 after treatment, mice were sacrificed, and the extent of injury was assessed through hematoxylin and eosin and Nissl staining, while the levels of pyroptosis markers and neuroinflammation in brain tissue were detected by immunohistochemistry. On day 21 after treatment, the Morris water maze was used to evaluate neural function recovery. Compared with the TBI group, high-dose ticagrelor treatment inhibited pyroptosis in mouse brain tissue, reduced the release of inflammatory cytokines, alleviated brain edema, lowered neuroinflammation levels, and promoted neural function recovery (P < 0.05). Therefore, ticagrelor holds promise as a clinical drug for treating TBI.

Acute cerebral infarction (CI) is characterized by acute onset, high disability rate, and high morbidity rate, which seriously threatens the health and safety of people and places a heavy burden on individuals and the country. This study aimed to explore the effects of butylphthalide on nerve cell ferroptosis in CI rats and its underlying mechanisms. Middle cerebral artery occlusion (MCAO) rat model was used to study the effect of butylphthalide on acute CI in vivo and oxygen glucose deprivation (OGD) model was used to study the effect of butylphthalide on acute CI in vitro. Our findings demonstrated that butylphthalide markedly reduced oxidative damage and ferroptosis in the brains of MCAO rats. Furthermore, we found that butylphthalide upregulated the netrin-1/deleted in colorectal cancer (DCC)/vascular endothelial growth factor (VEGF) signaling axis, which regulates NF-E2-related factor-2 (NRF2) expression and contributes to ferroptosis in the MCAO rat model and OGD-treated HT22 cells. Collectively, our findings indicate that butylphthalide inhibits oxidative stress-mediated ferroptosis in the MCAO rat model and OGD-treated HT22 cells by modulating the netrin-1/DCC/VEGF/NRF2 axis. In conclusion, our results reveal a novel mechanism for the protection of acute CIs by butylphthalide.