Neuroreport最新文献

Parkinson's disease with dementia (PDD) severely affects the quality of life of patients with Parkinson's disease (PD) in the later stages. Recently, PD patients with diabetes were found to have a higher risk of cognitive decline and developing dementia with a faster progression, but the underlying mechanism remains unclear. Diabetes-related white matter damage may partially explain the mechanism by which diabetes participates in PDD. Seventy PD patients were included. PD patients underwent diffusion tensor imaging from The Second Affiliated Hospital of Chongqing Medical University were collected and were divided into four groups: PD with diabetes without dementia, PD with dementia without diabetes, PD without dementia and diabetes. Tract-based spatial statistics analysis and region-of-interest-based analysis were performed. Factorial analysis with diabetes and dementia taken as the main effects was performed, and the differences between the white matter fibers of PD patients from the four groups were also analyzed. The interaction between diabetes and dementia in the damage of white matter in PD patients was also analyzed. We found that both diabetes and dementia were found to be related to the damage in internal capsule, corona radiata, and thalamic radiation of the PD patients. There is an interaction between diabetes and dementia in the white matter damage of PD patients. Both diabetes and dementia were found to be related to the damage in internal capsule, corona radiata, and thalamic radiation of the PD patients. Diabetes may participate in cognitive decline in PD patients via damaging cognition-related white matter tracts.

Ischemic stroke is the primary cause of mortality for individuals with disability worldwide. Tripartite motif 37 (TRIM37) plays multiple regulatory roles in various cellular processes. Our research aimed to investigate the effects of TRIM37 on the progression of ischemic stroke and its related mechanisms. Primary rat brain microvascular endothelial cells (BMECs) were treated with oxygen-glucose deprivation and reoxygenation (OGD/R) and then transduced with pShuttle-H1-TRIM37 shRNA plasmid, pShuttle-CMV-TRIM37 plasmid, or corresponding negative controls. The effects of TRIM37 were also explored in middle cerebral artery occlusion surgery-induced rat brain damage in vivo . Factor VIII staining showed the successful isolation of the primary BMECs. The OGD/R procedure significantly inhibited the cell viability and upregulated the TRIM37 expression in a time-dependent manner. In addition, OGD/R evidently increased the cell permeability, elevated the tumor necrosis factor alpha and intercellular adhesion molecule 1 levels, and upregulated the nuclear expression of nuclear factor (NF)-κB, but downregulated the peroxisome proliferator-activated receptors γ (PPARγ), zonula occludens-1, and cytoplasmic NF-κB expressions, which were reversed by TRIM37 knockdown. Furthermore, TRIM37 interacted with PPARγ and promoted its ubiquitination. The effects on cell permeability and inflammation induced by TRIM37 overexpression were reversed by PPARγ agonist. TRIM37 knockdown also inhibited middle cerebral artery occlusion-induced rat brain damage in vitro . TRIM37 may be a potential therapeutic target for ischemic stroke, and the knockdown of TRIM37 may improve brain injury by regulating the PPARγ/NF-κB pathway to modulate the inflammatory response.

This study aimed to examine reticulon 4 (RTN4), neurite outgrowth inhibitor protein expression that changes in high-altitude traumatic brain injury (HA-TBI) and affects on blood-brain barrier's (BBB) function. C57BL/6J 6-8-week-old male mice were used for TBI model induction and randomized into the normal altitude group and the 5000-m high-altitude (HA) group, each group was divided into control (C) and 8h/12h/24h/48h-TBI according to different times post-TBI. Brain water content (BWC) and modified Neurological Severity Score were measured, RTN4 and autophagy-related indexes (Beclin1, LC3B, and SQSTM1/p62) were detected by western blot, immunofluorescence technique, and PCR in peri-injury cortical tissues. The expression of NgR1, Lingo-1, TROY, P75, PirB, S1PR2, and RhoA receptors' downstream of RTN4 was detected by PCR. HA-TBI caused increased neurological deficits including motor, sensory, balance and reflex deficits, increased BWC, earlier peak RTN4 expression and a longer duration of high expression in peri-injury cortical tissues, and enhanced levels of Beclin1, LC3B, and SQSTM1/p62 to varying degrees. Concurrently, the transcription of S1PR2 and PirB, the main signaling molecules downstream of RTN4, was significantly increased. In HA-TBI's early stages, the increased RTN4 may regulate enhanced autophagic initiation and impaired autolysosome degradation in vascular endothelial cells via S1PR2 receptor activation, thereby reducing BBB function. This suggests that autophagy could be a new target using RTN4 intervention as a clinical HA-TBI mechanism.

Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening and life-limiting disease with high mortality and disability rates. Herein, we aim to explore the preventive effect of aminocaproic acid combined with nimodipine on short-term rebleeding in patients with aSAH. Retrospectively, the medical data of patients with aSAH ( n  = 256) were collected. According to different treatment methods, patients were categorized into the aminocaproic acid + nimodipine group ( n  = 152) and the nimodipine group ( n  = 104), and were treated for 1 week. Baseline characteristics, incidence of rebleeding, average velocity of cerebral artery blood flow, cerebral vasospasm index, vascular endothelial function, complications, and adverse events were analyzed between the two groups. After 1-week treatment, compared to the nimodipine group, the aminocaproic acid + nimodipine group exhibited lower incidence of rebleeding, notable decreases in average velocity of cerebral artery blood flow and the cerebral vasospasm index, and downregulation of endothelin-1 and vascular endothelial growth factor ( P  < 0.05). There were no significant differences about complications and adverse events between the two groups. Aminocaproic acid combined with nimodipine is superior to nimodipine alone in preventing the short-term rebleeding in patients with aSAH, and has good safety.

Noise-induced hearing loss (NIHL) constitutes a significant global health issue for which there is no effective treatment. The loss of cochlear hair cells and associated synaptopathy are common causes of hearing impairment. One primary mechanism implicated in NIHL is the accumulation of reactive oxygen species (ROS), which ultimately overwhelms cochlear cells. ROS are detected in the cochlea immediately after noise exposure and persist for at least a week. Within cells, ROS are primarily generated in mitochondria as byproducts of cellular metabolism. Elamipretide is a synthetic tetrapeptide known to concentrate in mitochondria, improving mitochondrial function and reducing ROS production. To test the hypothesis that elamipretide treatment mitigates NIHL, 16-week-old male and female CBA/J mice were exposed to 8-16 kHz octave-band noise (OBN) at 98 dB SPL for 2 hours. Elamipretide was administered intraperitoneally immediately after noise exposure and continued for 2 weeks. Efficacy was evaluated based on auditory brainstem response (ABR) thresholds, wave amplitudes, and wave latencies in treated and control groups. Results showed that OBN-exposed mice exhibited an elevation in ABR thresholds at 16 and 32 kHz and a reduction in ABR wave-I amplitude at 32 kHz, although wave-I latencies were not affected at 16 or 32 kHz. Elamipretide treatment prevented the OBN-induced elevation of ABR thresholds and the attenuation of wave-I amplitude. These findings provide proof of concept that mitochondrial-targeted elamipretide can prevent NIHL in a mammalian model and highlight its potential to protect against NIHL in humans.

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.

The present study aimed to investigate the therapeutic effects of electroacupuncture (EA) on chronic cerebral hypoperfusion (CCH). We first applied the Morris water maze approach to determine the effects of EA and TGN-020 [an inhibitor of aquaporin 4 (AQP4)] on the learning and memory ability of CCH rats. The hematoxylin and eosin, and Nissl staining were further used to investigate the effects of EA and TGN-020 on the neuropathological changes of the dentate gyrus. Next, the ELISA kits were adopted to determine the effects of EA and TGN-020 on the content of amyloid-beta (Aβ) in the cerebrospinal fluid of CCH rats. Finally, we respectively employed technologies of immunohistochemical staining, quantitative real-time PCR, and Western blot to further explore the effects of EA and TGN-020 on the mRNA expression level of amyloid precursor protein (APP) and AQP4 as well as the protein expression level of Aβ1-42 and AQP4 in the dentate gyrus of CCH rats. Our results indicated that EA not only enhanced the learning and memory abilities of CCH rats but also improved the neuropathological damages of CCH rats by upregulating the mRNA and protein expression level of AQP4 to reduce the accumulation of Aβ, especially for the reduction of the mRNA expression level of APP and the protein expression level of Aβ1-42, but TGN-020 effectively reversed the therapeutic effects mentioned above of EA. In summary, we proved that EA, as the activator of AQP4, prevents the accumulation of Aβ during the treatment of CCH.