Neuroreport最新文献

Even though considerable progress has been made to reduce insult, ischemic stroke is still a significant cause of mortality and morbidity in the world, and new therapeutic strategies are urgently needed. In the present study, the magnesium salt of salvianolic acid B (SalB) and ginsenoside Rg1 (Rg1) combination as a multicomponent strategy against stroke was evaluated. The synergistic effect of Sa1B and Rg1 was evaluated by Bliss independence analysis on the middle cerebral artery occlusion model. The infarct volume, neuroethology, cerebral structure, and neurocyte number were evaluated by 3,5-triphenyltetrazolium chloride staining, Longa score, Garcia score, hematoxylin-eosin staining, and Nissl staining, respectively. Metabolomics was used to search for potential biomarkers and explore the mechanism of Sa1B/Rg1. First, the superior effects of SalB/Rg1 than SalB or Rg1 at the same dose were evaluated. Compared with SalB ( P  < 0.001) or Rg1 ( P  < 0.01), SalB/Rg1 significantly decreased infarct volume through 3,5-triphenyltetrazolium chloride staining and protected the structural integrity of cortex and striatum. The superior effect of SalB/Rg1 on neurological behavior was also detected compared with SalB or Rg1 significantly. Accompanying behavioral improvement, a considerable increase of SalB/Rg1 on neurons detected by Nissl staining was found on the cortex compared with SalB ( P  < 0.05) or Rg1 ( P  < 0.01). Second, the synergistic effect between SalB and Rg1 was strictly verified by Bliss independence analysis ( P  < 0.01) based on infarct volume. Finally, alleviation of cerebral metabolic disorders may be the possible mechanism of SalB/Rg1. Our study provided a multicomponent strategy against ischemic stroke, with not only dose reduction but also improved efficacy relative to single agents.

Aging generally affects food consumption and energy metabolism. Since the feeding center is located in the hypothalamus, it is a major target for understanding the mechanism of age-related changes in eating behavior and metabolism. To obtain insight into the age-related changes in gene expression in the hypothalamus, we investigated genes whose expression changes with age in the hypothalamus. A DNA microanalysis was performed using hypothalamus samples obtained from young (aged 24 weeks) and old male mice (aged 138 weeks). Gene Ontology (GO) analysis was performed using the identified differentially expressed genes. We observed that the expression of 377 probe sets was significantly altered with aging (177 were upregulated and 200 were downregulated in old mice). As a result of the GO analysis of these probe sets, 16 GO terms, including the neuropeptide signaling pathway, were obtained. Intriguingly, although the food intake in old mice was lower than that in young mice, we found that several neuropeptide genes, such as agouti-related neuropeptide ( Agrp ), neuropeptide Y ( Npy ), and pro-melanin-concentrating hormone ( Pmch ), all of which promote food intake, were upregulated in old mice. In conclusion, this suggests that the gene expression pattern in the hypothalamus is regulated to promote food intake.

Dysregulated appetite is common in autism spectrum disorder (ASD) and it includes excessive interest in tasty foods. Overconsumption of palatable fluids has been found in the valproic acid-induced ASD rat. Though ASD has a strong genetic component, the link between ASD-related genes and appetite for palatable foods remains elusive. We focused on the CNTNAP2 gene whose deletion in mice recapitulates human ASD symptoms. We investigated whether Cntnap2-/- male mice consume greater amounts of palatable 10% sucrose, 0.1% saccharin, and 4.1% intralipid solutions offered in episodic meals either in a no-choice paradigm or a two-bottle choice test. We examined how sucrose intake affects c-Fos immunoreactivity in feeding-related brain areas. Finally, we determined doses at which intraperitoneal oxytocin decreases sucrose intake in mutants. In the single-bottle tests, Cntnap2-/- mice drank more sucrose, saccharin, and intralipid compared to WTs. Given a choice between two tastants, Cntnap2-/- mice had a higher preference for sucrose than intralipid. While the standard 1 mg/kg oxytocin dose reduced sucrose intake in WTs, a low oxytocin dose (0.1 mg/kg) decreased sucrose intake in Cntnap2-/- mice. Sucrose intake induced a more robust c-Fos response in wild-type (WT) than Cntnap2-/- mice in the reward and hypothalamic sites and it increased the percentage of Fos-immunoreactivity oxytocin neurons in WTs, but not in mutants. We conclude that Cntnap2-/- mice overconsume palatable solutions, especially sucrose, beyond levels seen in WTs. This excessive consumption is associated with blunted c-Fos immunoreactivity in feeding-related brain sites, and it can be reversed by low-dose oxytocin.

Previous studies have found alterations in the local regional homogeneity of brain activity in individuals diagnosed with major depressive disorder. However, many studies have failed to consider that even during resting states, brain activity is dynamic and time-varying. The lack of investigation into the dynamic regional homogeneity has hindered the discovery of biomarkers for depression. This study aimed to assess the utility of the dynamic regional homogeneity by a machine learning model (support vector machine). Sixty-five individuals with dynamic regional homogeneity and 57 healthy controls participated in resting-state functional magnetic resonance rescanning and scale estimating. The dynamic regional homogeneity and receiver operating characteristic curve methods were used for analysis of the imaging data. Relative to healthy controls, major depressive disorder patients displayed increased dynamic regional homogeneity values in the left precuneus and right postcentral gyrus. Additionally, receiver operating characteristic curve results of the dynamic regional homogeneity values in the left precuneus and right postcentral gyrus could distinguish major depressive disorder patients from healthy controls; furthermore, changes in the dynamic regional homogeneity were correlated with depression severity.

This study aimed to compare the effect of the early postmenopausal period on resting-state electroencephalographic spectral power with that of the premenopausal period and to analyze the correlation between electroencephalographic spectral power values and endogenous ovarian hormone levels. This study involved 13 early postmenopausal women and 10 premenopausal women in the early follicular, 10 in the ovulatory phase, and 10 in the early luteal phase who underwent resting-state quantitative electroencephalographic spectral power with eyes closed and endogenous ovarian hormone measurements. The delta, theta, alpha1, alpha2, beta1, and beta2 absolute power were compared between the early postmenopausal and premenopausal groups. Correlations between electroencephalographic spectral power values and 17β estradiol, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone levels were analyzed in early postmenopausal women. Compared with the premenopausal group, the early postmenopausal group showed significantly higher resting-state theta power in the frontal region, alpha1 and alpha2 power in the frontal and central regions, beta1 power in the frontal, central, parietal, and occipital regions, and beta2 power in the centroparietal region. Beta2 power values were positively correlated with FSH levels. The current findings highlight that early postmenopausal women show greater resting-state alpha and beta power, which suggests cortical excitability of fast frequency bands involved in states of alertness, focus of attention, cognition, and emotion. Additionally, we emphasized the effect of FSH levels on fast cortical activation in early postmenopausal women.

Thiamine deficiency is a well-known risk factor for the development of severe encephalopathy, such as Wernicke encephalopathy and Korsakoff syndrome, but the underlying mechanism is still mysterious. This study aims to investigate the expression levels of thiamine metabolism genes in different tissues and their impact on brain susceptibility to thiamine deficiency. The mRNA and protein levels of four genes known to be associated with thiamine metabolism: thiamine pyrophosphokinase-1 ( Tpk ), Solute carrier family 19 member 2 ( Slc19a2 ), Slc19a3 , and Slc25a19 , in the brain, kidney, and liver of mice were examined. Thiamine diphosphate (TDP) levels were measured in these tissues. Mice were subjected to dietary thiamine deprivation plus pyrithiamine (PTD), a specific TPK inhibitor, or pyrithiamine alone to observe the reduction in TDP and associated pathological changes. TPK mRNA and protein expression levels were lowest in the brain compared to the kidney and liver. Correspondingly, TDP levels were also lowest in the brain. Mice treated with PTD or pyrithiamine alone showed an initial reduction in brain TDP levels, followed by reductions in the liver and kidney. PTD treatment caused significant neuron loss, neuroinflammation, and blood-brain barrier disruption, whereas dietary thiamine deprivation alone did not. TPK expression level is the best indicator of thiamine metabolism status. Low TPK expression in the brain appears likely to contribute to brain susceptibility to thiamine deficiency, underscoring a critical role of TPK in maintaining cerebral thiamine metabolism and preventing thiamine deficiency-related brain lesions.

Previous studies have shown that cerebral ischemia can cause white matter injury in the brain. This study aimed to investigate the potential mechanism of electroacupuncture (EA) at the Baihui (GV20) and Zusanli (ST36) acupoints in protecting white matter. Sprague-Dawley rats were used to establish permanent middle cerebral artery occlusion (pMCAO) rat models. Comprehensive motor functions were assessed using the mesh experiment. Morphological changes in the myelin sheath were assessed with Luxol fast blue staining. Morphological changes in oligodendrocytes and myelinated axons were evaluated using Nissl staining. The expressions of high-mobility group box 1 protein (HMGB1) and the receptor for advanced glycation end products (RAGE) in the corpus callosum were detected by immunohistochemical staining and Western blot analysis. pMCAO caused severe injury to the corpus callosum, evidenced by significant loss of white matter fibers and myelinated axons, and induced overexpression of HMGB1 and RAGE in the corpus callosum. EA treatment significantly improved comprehensive motor function alleviated white matter damage, and downregulated the expression of HMGB1 and RAGE. Its effects were comparable to those of FPS-ZM1, a RAGE receptor inhibitor. In conclusion, EA effectively improves comprehensive motor function in rats with cerebral infarction and alleviates corpus callosum injury. This effect may be related to the inhibition of HMGB1 and RAGE overexpression.

Numerous behavioral studies have demonstrated a rhythmic priming effect (RPE) on grammatical processing using grammaticality judgment tasks (GJT), where participants performed better following regular rhythmic sequences compared to baseline conditions or irregular rhythmic sequences (i.e. auditory rhythmic sequences with violated metrical structure). Only a few studies, however, have explored neurophysiological RPE in grammatical processing. Such neurophysiological investigations have been limited to GJT presented auditorily, have been primarily focused on the French- and German-speaking adult participants, and have rarely used baseline nonpriming conditions. The objective of the present study was to investigate neurophysiological correlates of the RPE in the GJT presented in visual modality. In the current study, we registered a 128-channel electroencephalogram while Russian-speaking adolescents performed a visual GJT, where each sentence was presented word by word in a self-paced manner. Before each experimental block, participants listened to regular rhythmic sequences, irregular rhythmic sequences, or silence. We observed that the late negativity in the event-related potential was larger for the ungrammatical condition compared to the grammatical condition only after the presentation of irregular rhythmic sequences. This effect, referred to as the N600 component in previous research, has been associated with increased cognitive complexity. In conclusion, results suggest that exposure to irregular rhythmic stimulation may lead to increased cognitive demand. This is attributed to the complexity associated with concurrently executing the GJT and managing rhythmic disruption, consequently increasing the strain on working memory resources.

Ischemic stroke remains a major cause of disability and mortality. Nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy is involved in cerebral ischemic injury. Additionally, lactylation regulates the progression of ischemia injury. This study aimed to investigate the impact of NCOA4 on ferritinophagy and glycolysis of hippocampal neuron cells and its lactylation modification. Middle cerebral artery occlusion (MCAO) mouse and oxygen-glucose deprivation (OGD)-treated HT22 cell models were generated. Ferritinophagy was evaluated via detecting ferrous iron (Fe 2+ ), glutathione, malondialdehyde, and protein levels. Glycolysis was assessed by examining the glucose consumption, lactate production, and extracellular acidification rate. The lactylation was evaluated using immunoprecipitation and immunoblotting. Brain injury in vivo was analyzed by measuring brain infarct and neurological function. The results showed that NCOA4 expression was increased in the blood of patients with acute ischemia stroke, the peri-infarct region of the brain in MCAO mice (increased percentage: 142.11%) and OGD-treated cells (increased percentage: 114.70%). Knockdown of NCOA4 inhibited ferritinophagy and glycolysis of HT22 cells induced by OGD. Moreover, OGD promoted the lactylation of NCOA4 at lysine (K)450 sites, which enhanced NCOA4 protein stability. Additionally, interfering with NCOA4 attenuated brain infarction and neurological dysfunction in MCAO mice. Lactylation of NCOA4 at K450 sites promotes ferritinophagy and glycolysis of hippocampal neuron cells, thereby accelerating cerebral ischemic injury. These findings suggest a novel pathogenesis of ischemic stroke.