Navigating glioblastoma complexity: the interplay of neurotransmitters and chromatin.

Glioblastoma is the most aggressive brain cancer with an unfavorable prognosis for patient survival. Glioma stem cells, a subpopulation of cancer cells, drive tumor initiation, self-renewal, and resistance to therapy and, together with the microenvironment, play a crucial role in glioblastoma maintenance and progression. Neurotransmitters such as noradrenaline, dopamine, and serotonin have contrasting effects on glioblastoma development, stimulating or inhibiting its progression depending on the cellular context and through their action on glioma stem cells, perhaps changing the epigenetic landscape. Recent studies have revealed that serotonin and dopamine induce chromatin modifications related to transcriptional plasticity in the mammalian brain and possibly in glioblastoma; however, this topic still needs to be explored because of its potential implications for glioblastoma treatment. Also, it is essential to consider that neurotransmitters' effects depend on the tumor's microenvironment since it can significantly influence the response and behavior of cancer cells. This review examines the possible role of neurotransmitters as regulators of glioblastoma development, focusing on their impact on the chromatin of glioma stem cells.

Secondary analysis of neurotransmitter metabolism and cognitive function in first-diagnosed, drug-naïve adult patients with major depressive disorder.

BACKGROUND & AIMS: Growing evidence suggests that neurotransmitters may be associated with cognitive decline in MDD. This study primarily investigated the differences in cognitive functions between MDD patients and healthy controls, and explored the potential association between neurotransmitters and cognitive function of MDD patients. METHODS: This cross-sectional study enrolled 87 first-diagnosed and drug-naïve patients with MDD and 50 healthy controls. Neurotransmitters (glutamine, glutamic acid, γ-2Aminobutiric acid, kainate, vanillylmandelic acid (VMA), 3-methoxy 4-hydroxyphenyl ethylene glycol (MHPG), noradrenaline (NE), homovanillic acid, dihydroxy-phenyl acetic acid (DOPAC), dopamine (DA), tryptophane, kynurenine, 5-HT, 5-hydroxyindoleacetic acid) were measured using LC-MS/MS and cognitive functions were assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Then associative analyses with adjustment (female, age, BMI, education) by multiple linear regression between neurotransmitters and cognitive functions especially in MDD patients were performed. RESULTS: MDD patients had lower RBANS scores in immediate memory, delayed memory and RBANS scores after adjustment. Neurotransmitters were associated with the cognitive levels of MDD patients after adjustment: DOPAC and DOPAC/DA had positive association with immediate memory score; DOPAC, DOPAC/DA and (VMA+MHPG)/NE were positively associated with attention score; NE was negatively associated with language score; DOPAC/DA was positively associated with both delayed memory and RBANS scores. CONCLUSION: Patients had greater cognitive impairment especially in memory. Furthermore, plasma neurotransmitter may be related to MDD and play an important role in cognitive impairment in MDD, especially in memory and attention.

Effect of esketamine on serum neurotransmitters in patients with postpartum depression: a randomized controlled trial.

BACKGROUND: The development of postpartum depression has been linked to fluctuations in the levels of neurotransmitters in the human body, such as 5-hydroxytryptamine (5-HT), dopamine (DA), noradrenaline (Norepinephrine, NE), and brain derived neurotrophic factor (BDNF). Research has indicated that the antidepressant effect of esketamine are mediated by monoamine transmitters and neurotrophic factors. Therefore, we postulate that intravenous administration of esketamine in patients with postpartum depression may alter the serum concentrations of these neurotransmitters. METHODS: Three hundred fifteen patients with postpartum depression were selected and divided into two groups based on randomized numerical expression: esketamine (E) group (0. 25 mg/kg esketamine) and control (C) group (a same volume of 0.9% saline), all the drugs were pumped for 40 min. After the end of drug pumping, all patients were continuously observed for 2 h. Changes in serum levels of 5-HT, DA, NE, BDNF were recorded before drug administration and on the 3rd day after drug administration. The scores of Edinburgh Postnatal Depression Scale (EPDS) were calculated before drug administration, and on the 3rd day and on the 30th day after drug administration. Dizziness, headache, nausea, vomiting, drowsiness, and feeling of detachment occurred were recorded within 2 h after drug administration. RESULTS: Before drug administration, the serum concentrations of 5-HT,DA,BDNF,NE in Group E and Group C were namely (0. 91 ± 0. 19 vs. 0. 98 ± 0. 21, P = 0. 181), (2. 38 ± 0. 35 vs. 2. 32 ± 0. 32, P = 0. 491), (3. 07 ± 0. 89 vs 3. 02 ± 0. 88, P = 0. 828), (39. 79 ± 7. 78 vs 41. 34 ± 10. 03, P = 0. 506). On the third day post-medication, the serum concentrations of 5-HT,DA,BDNF,NE in Group E and Group C were namely (1. 42 ± 0. 35 vs. 0. 96 ± 0. 24, P < 0. 001), (3. 99 ± 0. 17 vs. 2. 41 ± 0. 28, P < 0. 001),(5. 45 ± 0. 81 vs 3. 22 ± 0. 76, P < 0. 001),(44. 36 ± 9. 98 vs 40. 69 ± 11. 75, P = 0. 198). Before medication, the EPDS scores were (16. 15 ± 3. 02 vs 17. 85 ± 3. 89, P = 0. 064). on the third day after medication, the Group E had significantly reduced scores (12. 98 ± 2. 39 vs 16. 73 ± 3. 52, P < 0. 001). On the 30rd day after medication, EPDS scores between the two groups were (16. 34 ± 3. 43 vs 16. 91 ± 4. 02, p = 0. 203). Within 2 h of medication, the rate of adverse events was similar between the two groups. CONCLUSIONS: Small doses of esketamine can increase the serum concentration of 5-HT,DA,BDNF, and in the short term, decrease EPDS scores, and improve postpartum depressive symptoms. TRIAL REGISTRATION: Retrospectively registered in the Chinese Clinical Trial Registry (ChiCTR2300078343, 2023/12/05).

Significance of Neurotransmitters in Cerebral Ischemia: Understanding the Role of Serotonin, Dopamine, Glutamate, and GABA in Stroke Recovery and Treatment.

Brain ischemia occurs following heart failure, thromboembolism, and atherosclerosis, and it is characterized by the disturbance of blood flow resulting from the blockage of blood vessels. After a series of studies, it is deduced that various changes occur following stroke, including neural death and changes in plasticity. Studies have reported that neurotransmitters tend to change following a stroke. These changes that occur surrounding the infarct area following a stroke can be considered new therapeutic targets for stroke rehabilitation. Although various studies have reported that different neurotransmitters have a promising role in either the progression or the rehabilitation following stroke, they have not found any pharmacological interventions to help the previous rehabilitation therapeutics. Phytocompounds also offer potential therapeutic benefits in stroke management due to their antioxidative and anti-inflammatory properties. This article aimed to compile recent advancements in neurotransmitter research related to ischemia and explore the potential use of neurotransmitter agonists/antagonists in ischemic conditions to identify potential drug candidates for treating the severe and prolonged stages of stroke in the future.

Exposure to thimerosal induces behavioral abnormality in the early life stages of zebrafish via altering amino acid homeostasis.

Thimerosal (THI) has become a significant source of organic mercury pollutants in aquatic ecosystems, but there is limited information regarding its adverse effects on fish. In this study, zebrafish embryos were exposed to THI at 0 (control), 5.0, and 50 ng/L from 0-5 days post fertilization (dpf), and variations in their survival, development, behavior, free amino acid contents, and the biochemical responses involved in monoaminergic systems were examined. Although THI exposure did not significantly affect the survival, heart rate, or hatching time of zebrafish embryos, it substantially increased swimming velocity (136-154 % of the control) and reduced exploratory behavior (141-142 % of the control) in zebrafish larvae at 5 dpf. Exposure also significantly altered the amino acid contents (51-209 % of the control) and monoamine levels (70-154 % of the control) in zebrafish larvae, some of which displayed significant correlations with behavioral traits. THI significantly elevated dopamine receptor gene expression and monoamine oxidase activity in zebrafish larvae. Adding extra phenylalanine or tryptophan to the E3 medium facilitates the recovery of zebrafish larvae from the abnormal behaviors induced by THI. These findings reveal for the first time that THI exposure at the level of ng/L is sufficient to induce neurobehavioral toxic effects in the early life stages of zebrafish, and disrupting amino acid homeostasis is a critical underlying mechanism. This study provides valuable insights into the toxicity of THI to fish and highlights the importance of assessing its potential risks to aquatic ecosystems.

1-Octanol-assisted ultra-small volume droplet microfluidics with nanoelectrospray ionization mass spectrometry.

BACKGROUND: Droplet microfluidics with push-pull and microdialysis sampling from brain slices, cultured cells and engineered tissues produce low volume mass limited samples containing analytes sampled from the extracellular space. This sampling approach coupled to mass spectrometry (MS) detection allows evaluation of time-dependent chemical changes. Our goal is an approach for continuous sampling and segregation of extracellular samples into picoliter droplets followed by the characterization of the droplets using nanoelectrospray ionization (nESI) MS. The main focus here is the optimization of the carrier oil for the microfluidic device that neither affects the stability of picoliter droplets nor compatibility with MS detection of a range of analytes. RESULTS: We developed and characterized a 1-octanol-assisted ultra-small volume droplet microfluidic nESI MS system for the analysis of neurotransmitters in distinct samples including cerebrospinal fluid (CSF). The use of a 1-octanol oil phase was effective for generation of aqueous droplets as small as 65 pL and enabled detection of acetylcholine (ACh) and gamma-aminobutyric acid (GABA) in water and artificial CSF. Continuous MS analysis of droplets for extended periods up to 220 min validated the long-term stability of droplet generation and analyte detection by nESI-MS. As an example, ACh response demonstrated a linear working range (R2 = 0.99) between 0.4 µM and 25 µM with a limit of detection of 370 nM (24 amol), enabling its quantitation in rodent CSF. SIGNIFICANCE: The established droplet microfluidics - nESI MS approach allows the analysis of microenvironments at high spatiotemporal resolution. The approach may allow microsampling and monitoring of spatiotemporal dynamics of neurochemicals and drugs in the brain and spinal cord of live animals.

The impact of exercise on depression: how moving makes your brain and body feel better.

PURPOSE: This study aimed to comprehensively explore and elucidate the intricate relationship between exercise and depression, and focused on the physiological mechanisms by which exercise influences the brain and body to alleviate depression symptoms. By accumulating the current research findings and neurobiological insights, this study aimed to provide a deeper understanding of the therapeutic potential of exercise in the management and treatment of depression. METHODS: We conducted a systematic review of the scientific literature by selecting relevant studies published up to October 2023. The search included randomized controlled trials, observational studies, and review articles. Keywords such as "exercise," "depression," "neurobiology," "endocrinology," and "physiological mechanisms" were used to identify pertinent sources. RESULTS: Inflammation has been linked to depression and exercise has been shown to modulate the immune system. Regular exercise can (1) reduce the levels of pro-inflammatory cytokines, potentially alleviating depressive symptoms associated with inflammation; (2) help in regulating circadian rhythms that are often disrupted in individuals with depression; and (3) improve sleep patterns, thus regulating mood and energy levels. CONCLUSION: The mechanisms by which exercise reduces depression levels are multifaceted and include both physiological and psychological factors. Exercise can increase the production of endorphins, which are neurotransmitters associated with a positive mood and feelings of well-being. Exercise improves sleep, reduces stress and anxiety, and enhances self-esteem and social support. The implications of exercise as a treatment for depression are significant because depression is a common and debilitating mental health condition. Exercise is a low-cost, accessible, and effective treatment option that can be implemented in various settings such as primary care, mental health clinics, and community-based programs. Exercise can also be used as an adjunctive treatment along with medication and psychotherapy, which can enhance treatment outcomes.

Protective effects of a probiotic-fermented germinated grain complex on neurotransmitters and sleep quality in sleep-deprived mice.

Objective: To explore the effects of probiotic fermentation products of germinated grains on cognitive and sleep improvement in mice with sleep deprivation induced by chlorophenylalanine (PCPA), and to provide theoretical and experimental basis for the development of natural products to alleviate insomnia. Methods: ELISA and high-performance liquid chromatography (HPLC) were used to determine the contents of γ-aminobutyric acid and L-theanine in fermentation products. Open Field Test was used to analyze the changes of emotional behavior between groups before and after intervention. ELISA was used to analyze the changes of hypothalamic serotonin, GABA, glutamate, and serum interleukin 6. 16S rRNA sequencing was used to analyze the changes of intestinal flora before and after the intervention of compound fermentation products. LC-MS/MS was used to analyze the changes of intestinal SCFAs before and after the intervention. Results: The content of GABA and L-theanine in 7 L fermentation products was 12.555 µmol/L (1.295 mg/L) and 0.471 mg/mL by ELISA. Compared with the PCPA-induced Model group, the sleep duration of the KEY group was statistically significant (p < 0.0001). Compared with the PCPA-induced Model group, the number of crossing the central lattice in the KEY group was significantly increased, and the number of grooming was significantly reduced (all p < 0.05), suggesting that the anxiety behavior of the mice was improved. In addition, this study found that the compound fermentation products could significantly increase the content of neurotransmitters such as 5-HT, GABA and Glu in the hypothalamus of mice, reduce the content of inflammatory factors such as IL-6, IL-1ß and TNF-α in serum, regulate the structure of intestinal flora and increase the content of short-chain fatty acids. Conclusion: Probiotic fermentation products of germinated grains can significantly improve sleep deprivation in PCPA mice, which may be related to regulating the levels of neurotransmitters and inflammatory factors, improving the structure of intestinal flora, and increasing the content of short-chain fatty acids. This study provides new candidates and research directions for the development of natural drugs to alleviate insomnia.

[Effects of acupuncture on endothelial active factors and related autonomic neurotransmitters in spontaneous hypertension rats].

OBJECTIVE: To observe the effects of acupuncture at "antihypertensive acupoint prescription" on endothelial active factors and related autonomic neurotransmitters in spontaneous hypertension rats, and explore the vascular regulation and central regulation mechanisms of acupuncture for anti-hypertension. METHODS: Thirty SPF grade male spontaneous hypertension rats were randomly divided into a model group (15 rats) and an acupuncture group (15 rats). Besides, 15 Wistar Kyoto rats were collected as a blank control group (normal group). In the acupuncture group, acupuncture was delivered at the "antihypertensive acupoint prescription" (bilateral "Renying" [ST 9], "Quchi" [LI 11], "Zusanli" [ST 36], "Taichong" [LR 3] and "Neiguan" [PC 6]), with needles retained for 30 min, once daily. The duration of intervention was 28 days. Every week, using the the irritation scale, the sign of sympathetic irritation was evaluated dynamically. The arterial blood pressure of the rats tail was determined, using non-invasive blood pressure measurement system. ELISA was adopted to detect the levels of calcitonin gene-related peptide (CGRP), nitric oxide (NO), endothelin-1 (ET-1), neuropeptide Y (NPY) in the serum. DAB chromogenic in situ hybridization (CISH) was provided to detect the mRNA expression of endothelial nitric oxide synthase (eNOS) in the internal carotid artery and the arcuate nucleus (ARC), and that of CGRP in the paraventricular nucleus posterior (PVP) and the ventrolateral medulla (VLM). Liquid chromatography-mass spectrometry (LC-MS) was used to detect the levels of epinephrine (E) and norepinephrine (NE) in the paraventricular nucleus anterior (PVA). RESULTS: Compared with the normal group, the irritation scores, systolic blood pressure and diastolic blood pressure were increased at each time point in the model group (P<0.05). When compared with the model group, the irritation scores after the intervention for 3 and 4 weeks, and systolic and diastolic blood pressure after intervention for 2, 3 and 4 weeks were reduced in the acupuncture group (P<0.05). In comparison with the normal group, the serum CGRP and NO levels of the rats were decreased (P<0.05), and the serum ET-1 and NPY levels, as well as E and EN levels in PVA were increased (P<0.05) in the model group. The levels of serum CGRP and NO were elevated (P<0.05), and the serum ET-1 and NPY levels, as well as E and EN levels of PVA were reduced (P<0.05) in the acupuncture group when compared with those of the model group. In the model group, the media of internal carotid artery exhibited thickening and remodeling, while the neuron volume in ARC was small. In the acupuncture group, every layer of internal carotid artery was acceptably arranged, and the parvicellular neuron of ARC was moderate in volume. For the in situ hybridization of eNOS mRNA for the rats of each group, the smooth muscle cells were predominantly expressed in each layer of the internal carotid artery, whereas the expression of parvicellular neurons was dominated in ARC. In the model group, the large and small neurosecretory cells were distributed sparsely in the nerves of PVP; in the acupuncture group, the cells of these two species were distributed regularly; and there were few species of glial cell in the VLM of either the model group or the acupuncture group. In each group, for the in situ hybridization of CGRP mRNA, the small neurosecretory cells were expressed predominately in the PVP, while, the expression of glial cell nuclei and the cell cytoplasm was dominated in the VLM. Compared with the normal group, the mRNA expression of eNOS in the internal carotid artery and ARC and that of CGRP mRNA in the PVP and VLM was decreased in the model group (P<0.05). In the acupuncture group, when compared with the model group, the mRNA expression of eNOS in the internal carotid artery and ARC and that of CGRP in the PVP and VLM was increased in the acupuncture group (P<0.05). CONCLUSION: Acupuncture at "antihypertensive acupoint prescription" can upregulate the level of vascular relaxing factors, downregulate the level of contracting factors, enhance the response of relaxing factors in targeting blood vessels and regulating the center. The mechanism may be related to the modulation of the sympathetic-adrenergic autonomic neurotransmitters in the paraventricular nucleus in spontaneous hypertension rats.

Novel mimetic tissue standards for precise quantitative mass spectrometry imaging of drug and neurotransmitter concentrations in rat brain tissues.

Understanding the relationship between the concentration of a drug and its therapeutic efficacy or side effects is crucial in drug development, especially to understand therapeutic efficacy in central nervous system drug, quantifying drug-induced site-specific changes in the levels of endogenous metabolites, such as neurotransmitters. In recent times, evaluation of quantitative distribution of drugs and endogenous metabolites using matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry imaging (MSI) has attracted much attention in drug discovery research. However, MALDI-MSI quantification (quantitative mass spectrometry imaging, QMSI) is an emerging technique, and needs to be further developed for practicable and convenient use in drug discovery research. In this study, we developed a reliable QMSI method for quantification of clozapine (antipsychotic drug) and dopamine and its metabolites in the rat brain using MALDI-MSI. An improved mimetic tissue model using powdered frozen tissue for QMSI was established as an alternative method, enabling the accurate quantification of clozapine levels in the rat brain. Furthermore, we used the improved method to evaluate drug-induced fluctuations in the concentrations of dopamine and its metabolites. This method can quantitatively evaluate drug localization in the brain and drug-induced changes in the concentration of endogenous metabolites, demonstrating the usefulness of QMSI.

A New BODIPY-Based Receptor for the Fluorescent Sensing of Catecholamines.

The human body synthesizes catecholamine neurotransmitters, such as dopamine and noradrenaline. Monitoring the levels of these molecules is crucial for the prevention of important diseases, such as Alzheimer's, schizophrenia, Parkinson's, Huntington's, attention-deficit hyperactivity disorder, and paragangliomas. Here, we have synthesized, characterized, and functionalized the BODIPY core with picolylamine (BDPy-pico) in order to create a sensor capable of detecting these biomarkers. The sensing properties of the BDPy-pico probe in solution were studied using fluorescence titrations and supported by DFT studies. Catecholamine sensing was also performed in the solid state by a simple strip test, using an optical fiber as the detector of emissions. In addition, the selectivity and recovery of the sensor were assessed, suggesting the possibility of using this receptor to detect dopamine and norepinephrine in human saliva.

Surface-Enhanced Raman Scattering Nanosensing and Imaging in Neuroscience.

Monitoring neurochemicals and imaging the molecular content of brain tissues in vitro, ex vivo, and in vivo is essential for enhancing our understanding of neurochemistry and the causes of brain disorders. This review explores the potential applications of surface-enhanced Raman scattering (SERS) nanosensors in neurosciences, where their adoption could lead to significant progress in the field. These applications encompass detecting neurotransmitters or brain disorders biomarkers in biofluids with SERS nanosensors, and imaging normal and pathological brain tissues with SERS labeling. Specific studies highlighting in vitro, ex vivo, and in vivo analysis of brain disorders using fit-for-purpose SERS nanosensors will be detailed, with an emphasis on the ability of SERS to detect clinically pertinent levels of neurochemicals. Recent advancements in designing SERS-active nanomaterials, improving experimentation in biofluids, and increasing the usage of machine learning for interpreting SERS spectra will also be discussed. Furthermore, we will address the tagging of tissues presenting pathologies with nanoparticles for SERS imaging, a burgeoning domain of neuroscience that has been demonstrated to be effective in guiding tumor removal during brain surgery. The review also explores future research applications for SERS nanosensors in neuroscience, including monitoring neurochemistry in vivo with greater penetration using surface-enhanced spatially offset Raman scattering (SESORS), near-infrared lasers, and 2-photon techniques. The article concludes by discussing the potential of SERS for investigating the effectiveness of therapies for brain disorders and for integrating conventional neurochemistry techniques with SERS sensing.

Neuroimmune circuits in the plaque and bone marrow regulate atherosclerosis.

Atherosclerosis remains the leading cause of death globally. Although its focal pathology is atheroma that develops in arterial walls, atherosclerosis is a systemic disease involving contributions by many organs and tissues. It is now established that the immune system causally contributes to all phases of atherosclerosis. Recent and emerging evidence positions the nervous system as a key modulator of inflammatory processes that underly atherosclerosis. This neuro-immune crosstalk, we are learning, is bidirectional, and immune regulated afferent signaling is becoming increasingly recognized in atherosclerosis. Here, we summarize data and concepts that link the immune and nervous systems in atherosclerosis by focusing on two important sites, the arterial vessel and the bone marrow.

Effect of acupuncture on post-stroke dysphagia: a randomized controlled trial.

Introduction: Post-stroke dysphagia (PSD) is associated with various complications that increase morbidity and mortality rates. Acupuncture has been used extensively in China to treat these complications; however, its therapeutic efficacy remains uncertain. We therefore aimed to study the clinical effects of acupuncture on PSD. Methods: Patients (n = 101) were randomly divided into acupuncture (n = 50) and rehabilitation training control (n = 51) groups based on the treatment used. Both groups were treated once daily, 6 days a week, for a total of 4 weeks. Pulse oxygen saturation (SpO2) and standardized swallowing assessment (SSA) were performed before the intervention, 2 weeks into treatment, after the intervention (4 weeks post-intervention), and at a 6-month follow-up (28 weeks). The levels of hemoglobin (Hb) and albumin (ALB), and 5-hydroxytryptamine (5-HT) and dopamine (DA) were measured before the intervention, 2 weeks into treatment, and after the intervention (4 weeks), as nutrition and swallowing function indices, respectively. Results: Following the intervention, significant differences were observed between the acupuncture and control groups. The acupuncture group exhibited considerably superior enhancements in SpO2 and SSA scores at 4 weeks (p < 0.001). Moreover, this group demonstrated significantly greater improvements in Hb, ALB, 5-HT, and DA values 4 weeks post-treatment (p < 0.001). However, sex-based differences were not observed (P > 0.005). Conclusion: Acupuncture treatment can improve the swallowing function and nutritional status of patients with PSD, and increase the levels of 5-HT and DA. These findings strongly support the efficacy of acupuncture as a therapeutic intervention in patients with PSD.Clinical trial registration: identifier, ChiCTR2100052201. (https://www.chictr.org.cn/).

Omega-3 Attenuates Disrupted Neurotransmission and Partially Protects Metabolic Dysfunction Caused by Obesity in Wistar Rats.

Omega-3 (n3) is a polyunsaturated fatty acid well known for its anti-inflammatory and neuroprotective properties. Obesity is linked to chronic inflammation that disrupts metabolism, the intestine physiology and the central nervous system functioning. This study aims to determine if n3 supplementation can interfere with the effects of obesity on the mitochondrial activity, intestinal barrier, and neurotransmitter levels in the brain of Wistar rats that received cafeteria diet (CAF). We examined adipose tissue, skeletal muscle, plasma, intestine, and the cerebral cortex of four groups: CT (control diet), CTn3 (control diet with n3 supplementation), CAF, and CAFn3 (CAF and n3). Diets were offered for 13 weeks, with n3 supplementation in the final 5 weeks. Adipose tissue Electron Transport Chain complexes I, II, and III showed higher activity in CAF groups, as did complexes III and IV in skeletal muscle. Acetate levels in plasma were reduced in CAF groups, and Lipopolysaccharide (LPS) was higher in the CAF group but reduced in CAFn3 group. Claudin-5 in the intestine was lower in CAF groups, with no n3 supplementation effect. In the cerebral cortex, dopamine levels were decreased with CAF, which was reversed by n3. DOPAC, a dopamine metabolite, also showed a supplementation effect, and HVA, a diet effect. Serotonin levels increased in the CAF group that received supplementation. Therefore, we demonstrate disturbances in mitochondria, plasma, intestine and brain of rats submitted to CAF and the potential benefit of n3 supplementation in endotoxemia and neurotransmitter levels.

Multi-walled carbon nanotubes-metal-organic framework nanocomposite based sensor for the monitoring of multiple monoamine neurotransmitters in living cells.

The levels of monoamine neurotransmitters (MNTs) including dopamine (DA), adrenaline (Adr), norepinephrine (NE) and 5-hydroxytryptamine (5-HT) in cells are useful indicators to explore the pathogenesis of MNTs-related diseases such as Alzheimer's disease, Parkinson's disease and depression. Herein, we constructed a novel electrochemical sensing platform based on multi-walled carbon nanotubes (MWCNTs)-amine functionalized Zr (IV) metal-organic framework (UIO-66-NH2) nanocomposite for the detection of multiple MNTs including DA, Adr, NE and 5-HT. The synergistic effect between MWCNTs and UIO-66-NH2 endowed the nanocomposite with high specific surface area, low interface impedance and superior electrocatalytic activity, which effectively enhance the electrochemical performance of the sensor. The MWCNTs-UIO-66-NH2 nanocomposite-based sensor exhibited satisfied sensitivity for the quantitative measurement of DA, Adr, NE and 5-HT, as well as low detection limit. The outstanding biocompatibility of the constructed sensor permitted it to be successfully implemented for the real-time monitoring of DA released by PC12 and C6 cells, providing a promising strategy for clinical diagnosis of MNTs-related disorders and diseases.

Long Mu Qing Xin mixture improves behavioral performance in spontaneously hypertensive rats (SHR/NCrl) by upregulating catecholamine neurotransmitters in prefrontal cortex and striatum via DRD1/cAMP/PKA-CREB signaling pathway.

Background: Attention deficit hyperactivity disorder (ADHD), a prevalent neurodevelopmental disorder in children, can be effectively alleviated by the herbal preparation Long Mu Qing Xin Mixture (LMQXM), but its mechanism has not been fully elucidated. Objective: To scrutinize the potential pharmacological mechanisms by which LMQXM improves behavior in spontaneously hypertensive rats (SHR/NCrl). Methods: The SHR/NCrl rats were randomly stratified into the model (SHR) group, the methylphenidate hydrochloride (MPH) group, and groups subjected to varying dosages of LMQXM into the medium dose (MD) group with a clinically effective dose, the low dose (LD) group with 0.5 times the clinically effective dose, and high dose (HD) group with 2 times the clinically effective dose. Furthermore, the WKY/NCrl rats constituted the control group. The evaluation of behavior involved the open field test and the Morris water maze test. HPLC, LC-MS, ELISA, immunohistochemistry, Western blot, and RT-qPCR were utilized to scrutinize the catecholamine neurotransmitter content and the expression of proteins and genes associated with the dopamine receptor D1 (DRD1)/cAMP/protein kinase A (PKA)-cAMP response element-binding (CREB) pathway in prefrontal cortex (PFC) and striatum. Results: MPH and LMQXM ameliorated hyperactivity and learning and memory deficits of SHR/NCrl rats. Among them, LMQXM-MD and MPH also upregulated dopamine (DA), norepinephrine (NE), adenylate cyclase (AC) and cAMP levels, and the expression of proteins and genes associated with the DRD1/cAMP/PKA-CREB pathway in PFC and striatum of SHR/NCrl rats. PFC and striatum DA levels were also upregulated in the LMQXM-LD group as well as the striatum DA levels in the LMQXM-HD group, but there were no statistically significant differences in their NE levels compared to the SHR group. LMQXM-LD and LMQXM-HD also upregulated some DRD1/cAMP/PKA-CREB pathway-related proteins and gene expression, but the effects were discernibly disparate in PFC and striatum. Upon comprehensive analysis, LMQXM-MD appeared to be the most effective dose. Conclusion: Our study tentatively suggests that LMQXM may rectify hyperactivity and learning and memory deficits of SHR/NCrl rats by elevating catecholamine neurotransmitters in the PFC and striatum. This effect may be attributed to the potential activation of the DRD1/cAMP/PKA-CREB signaling pathway, which appears to achieve an optimal response at moderate doses.

Correlation between cerebral neurotransmitters levels by proton magnetic resonance spectroscopy and HbA1c in patients with type 2 diabetes.

BACKGROUND: Cognitive dysfunction is the main manifestation of central neuropathy. Although cognitive impairments tend to be overlooked in patients with diabetes mellitus (DM), there is a growing body of evidence linking DM to cognitive dysfunction. Hyperglycemia is closely related to neurological abnormalities, while often disregarded in clinical practice. Changes in cerebral neurotransmitter levels are associated with a variety of neurological abnormalities and may be closely related to blood glucose control in patients with type 2 DM (T2DM). AIM: To evaluate the concentrations of cerebral neurotransmitters in T2DM patients exhibiting different hemoglobin A1c (HbA1c) levels. METHODS: A total of 130 T2DM patients were enrolled at the Department of Endocrinology of Shanghai East Hospital. The participants were divided into four groups according to their HbA1c levels using the interquartile method, namely Q1 (< 7.875%), Q2 (7.875%-9.050%), Q3 (9.050%-11.200%) and Q4 (≥ 11.200%). Clinical data were collected and measured, including age, height, weight, neck/waist/hip circumferences, blood pressure, comorbidities, duration of DM, and biochemical indicators. Meanwhile, neurotransmitters in the left hippocampus and left brainstem area were detected by proton magnetic resonance spectroscopy. RESULTS: The HbA1c level was significantly associated with urinary microalbumin (mALB), triglyceride, low-density lipoprotein cholesterol (LDL-C), homeostasis model assessment of insulin resistance (HOMA-IR), and beta cell function (HOMA-ß), N-acetylaspartate/creatine (NAA/Cr), and NAA/choline (NAA/Cho). Spearman correlation analysis showed that mALB, LDL-C, HOMA-IR and NAA/Cr in the left brainstem area were positively correlated with the level of HbA1c (P < 0.05), whereas HOMA-ß was negatively correlated with the HbA1c level (P < 0.05). Ordered multiple logistic regression analysis showed that NAA/Cho [Odds ratio (OR): 1.608, 95% confidence interval (95%CI): 1.004-2.578, P < 0.05], LDL-C (OR: 1.627, 95%CI: 1.119-2.370, P < 0.05), and HOMA-IR (OR: 1.107, 95%CI: 1.031-1.188, P < 0.01) were independent predictors of poor glycemic control. CONCLUSION: The cerebral neurotransmitter concentrations in the left brainstem area in patients with T2DM are closely related to glycemic control, which may be the basis for the changes in cognitive function in diabetic patients.

Research Progress on the Association between Schizophrenia and Toxoplasma gondii Infection.

Toxoplasma gondii( T. gondii or Tg), is an obligatory intracellular parasite with humans as its intermediate hosts. In recent years, significant correlations between T. gondii infection and schizophrenia have been reported, including the possible mediating mechanisms. Currently, mechanisms and hypotheses focus on central neurotransmitters, immunity, neuroinflammation, and epigenetics; however, the exact underlying mechanisms remain unclear. In this article, we review the studies related to T. gondii infection and schizophrenia, particularly the latest research progress. Research on dopamine (DA) and other neurotransmitters, the blood-brain barrier, inflammatory factors, disease heterogeneity, and other confounders is also discussed. In addition, we also summarized the results of some new epidemiological investigations.

Hematological and neurological impact studies on the exposure to naturally occurring radioactive materials.

Naturally Occurring Radioactive Materials (NORM) contribute to everyone's natural background radiation dose. The technologically advanced activities of the gas and oil sectors produce considerable amounts of radioactive materials as industrial by-products or waste products. The goal of the current study is to estimate the danger of long-term liability to Technologically Enhanced Naturally Occurring Radioactive Materials (TE-NORM) on blood indices, neurotransmitters, oxidative stress markers, and ß-amyloid in the cerebral cortex of rats' brains. Twenty adult male albino rats were divided into two equal groups (n = 10): control and irradiated. Irradiated rats were exposed to a total dose of 0.016 Gy of TE-NORM as a whole-body chronic exposure over a period of two months. It should be ''The results showed no significant changes in RBC count, Hb concentration, hematocrit percentage (HCT%), and Mean Corpuscular Hemoglobin Concentration (MCHC). However, there was a significant increase in the Mean Corpuscular Volume of RBCs (MCV) and a significant decrease in cell distribution width (RDW%) compared to the control. Alteration in neurotransmitters is noticeable by a significant increase in glutamic acid and significant decreases in serotonin and dopamine. Increased lipid peroxidation, decreased glutathione content, superoxide dismutase, catalase, and glutathione peroxidase activities indicating oxidative stress were accompanied by increased ß-amyloid in the cerebral cortex of rats' brains. The findings of the present study showed that chronic radiation liability has some harmful effects, that may predict the risks of future health problems in occupational radiation exposure in the oil industries. Therefore, the control of exposure and application of sample dosimetry is recommended for health and safety.