OBJECTIVE: Meningiomas are predominantly benign, but some cases exhibit recurrent growth after surgery and undergo malignant transformation to WHO grade 2 or grade 3. Despite progress in genetic analyses, advancements in metabolomic analysis remain less established. Herein, the authors investigated metabolic activity differences between WHO grade 1 meningiomas and WHO grade 2 or 3 meningiomas by noninvasively using proton magnetic resonance spectroscopy (1H-MRS), aiming to preoperatively estimate malignancy. They also reviewed the literature to elucidate this aspect of meningioma research.
METHODS: At Ryukyu University Hospital, the authors focused on 93 patients diagnosed with meningioma between 2011 and 2021. The inclusion criteria encompassed prior surgery, pathological diagnoses of meningioma, and preoperative 1H-MRS. Group I included 71 patients with WHO grade 1 meningioma and group II included 22 patients, comprising 19 and 3 with WHO grade 2 and 3 meningioma, respectively. The authors retrospectively conducted a comparative analysis of patient backgrounds and tumor metabolites.
RESULTS: Group I and II did not differ significantly in terms of patient demographic characteristics (age and sex). Group II demonstrated a significantly lower extent of tumor resection (p < 0.01), higher MIB-1 labeling index (LI) (p < 0.05), higher incidence of prior irradiation (p < 0.001), and increased rate of tumor recurrence (p = 0.005) compared to group I. According to 1H-MRS, all metabolites, except lactate, displayed significantly higher median creatine (Cr) ratios in group II than group I: glutamine/Cr was 8.46, glutamate/Cr was 9.49, lipid/Cr was 11.36, and choline/Cr was 2.77. According to the receiver operating characteristic (ROC) analysis, glutamine had the largest area under the curve of 0.765 among 10 metabolites, and the cutoff value for distinguishing between group I and II was 5.76.
CONCLUSIONS: In cases pathologically graded as WHO grade 2 or 3 meningiomas, metabolic products such as glutamine, glutamate, lipids, and choline increased significantly. These changes were correlated with elevation of the MIB-1 LI. In group II, the mean MIB-1 LI was 8.58, significantly higher than in group I, suggesting a strong association with pathological malignancy. Therefore, 1H-MRS may help to noninvasively predict tumor metabolic activity and tumor recurrence. Furthermore, the authors concluded from the ROC analysis that glutamine may be a potential indicator of future growth of meningioma and benefits of early surgery.

Many features of major depressive disorder are mirrored in rodent models of psychological stress. These models have been used to examine the relationship between the activation of the hypo- thalamic-pituitary axis in response to stress, the development of oxidative stress and neuroinflamma- tion, the dominance of cholinergic neurotransmission and the associated increase in REM sleep pres- sure. Rodent models have also provided valuable insights into the impairment of glycolysis and brain glucose utilization by the brain under stress, the resulting decrease in brain energy production and the reduction in glutamate/GABA -glutamine cycling. The rapidly acting antidepressants, scopolamine, ketamine and ECT, all raise extracellular glutamate and scopolamine and ketamine have specifically been shown to increase glutamate/GABA-glutamine cycling in men and rodents with corresponding short-term relief of depression. The nightly use of gammahydroxybutyrate (GHB) may achieve more permanent results and may even act prophylactically to prevent the development or recurrence of de- pression. GHB is a GABAB agonist and restores the normal balance between cholinergic and mono- aminergic neurotransmission by inhibiting cholinergic neurotransmission. It relieves REM sleep pres- sure. GHB\'s metabolism generates NADPH, a key antioxidant cofactor. Its metabolism also generates succinate, the tricarboxylic acid cycle intermediate, to provide energy to the cell and to synthesize glu- tamate. In both animals and man, GHB increases the level of brain glutamate.

BACKGROUND: Acori graminei Rhizoma is a commonly used traditional Chinese medicine for treating TD, with its main component being calamus volatile oil. Volatile Oil from Acori graminei Rhizoma(VOA)can protect nerve cells and alleviate learning and memory disorders. However, the mechanism of anti-tic of VOA is still unclear.
OBJECTIVE: We aimed to explore the effects of Volatile Oil from Acori Tatarinowii Rhizoma (VOA) on striatal dopaminergic and glutamatergic systems and synaptic plasticity of rats with Tic Disorder (TD), as well as its pharmaceutical mechanism against TD.
METHODS: This study involved 48 (three-week-old) Sprague Dawley (SD) rats, which were randomly divided into two primary groups: Control (8) and TD (40). Rats in the TD group were injected intraperitoneally with 3,3-iminodipropionitrile (IDPN) to construct the TD rat model. They were divided into five subgroups: Model, Tiapride, VOA-high, VOA-medium, and VOA-low (N=8). After modeling, VOA was administrated to rats in the VOA groups through gavage (once/day for four consecutive weeks), while rats in the blank control and model groups received normal saline of the same volume. The animals\' behavioral changes were reflected using the stereotypic and motor behavior scores. After interferences, patterns of striatal neurons and the density of dendritic spines were investigated using H&E and Golgi staining, and the ultrastructure of striatal synapses was examined using Transmission Electron Microscopy (TEM). Furthermore, Ca2+ content was determined using the Ca2+ detector, and Dopamine (DA) and Glutamate (GLU) contents in serum and striatum were detected through ELISA. Finally, DRD1, DRD2, AMPAR1, NMPAR1, DAT, VMAT2, CAMKⅡ, and CREB expression in the striatum was detected using Quantitative real-time PCR (qRT-PCR),Western Blotting (WB) and Immunohistochemical (IHC) methods.
RESULTS: Compared to rats in the blank control and model groups, rats in the VOA groups showed lower stereotypic behavior scores. Furthermore, rats in the VOA groups exhibited relieved, neuron damage and increased quantities of neuronal dendrites and dendritic spines Additionally, based on TEM images show that, the VOA groups showed a clear synaptic structure and increased amounts of postsynaptic dense substances and synaptic vesicles. The VOA groups also exhibited reduced Ca2+ contents, and upregulation of DRD1, DRD2, DAT, AMPAR1, and NMPAR1 and downregulation of VMAT-2, CAMKⅡ, and CREB in the striatum.
CONCLUSIONS: In summary, VOA could influence synaptic plasticity by tuning the dopaminergic and glutamatergic systems, thus relieving TD.

Chemosensory cells across the body of Drosophila melanogaster evaluate the environment to prioritize certain behaviors. Previous mapping of gustatory receptor neurons (GRNs) on the fly labellum identified a set of neurons in L-type sensilla that express Ionotropic Receptor 94e (IR94e), but the impact of IR94e GRNs on behavior remains unclear. We used optogenetics and chemogenetics to activate IR94e neurons and found that they drive mild feeding suppression but enhance egg laying. In vivo calcium imaging revealed that IR94e GRNs respond strongly to certain amino acids, including glutamate, and that IR94e plus co-receptors IR25a and IR76b are required for amino acid detection. Furthermore, IR94e mutants show behavioral changes to solutions containing amino acids, including increased consumption and decreased egg laying. Overall, our results suggest that IR94e GRNs on the fly labellum discourage feeding and encourage egg laying as part of an important behavioral switch in response to certain chemical cues.

Introduction: The chronic use of psychostimulants increases the risk of addiction and, there is no specific pharmacologic treatment for psychostimulant addiction. The vasopressin (AVP) system is a possible pharmacological target in drug addiction. Previous results obtained in our laboratory showed that amphetamine (AMPH) treatment decreases lateral septum (LS) AVP levels in male rats, and AVP microinjection in LS decreases addictive-like behavior. The aim of the present work was to investigate the effect of AMPH treatment on LS AVP levels and the effect of LS AVP administration on the expression of AMPH-conditioned place preference (CPP) in female rats. The secondary objectives were to study the effect of LS AVP administration on LS GABA and glutamate release in male and female rats and on nucleus accumbens (NAc) dopamine (DA) release in female rats. Methods: Female rats were conditioned with AMPH (1.5 mg/kg i.p.) or saline for 4 days. Results: Conditioning with AMPH did not change LS AVP content in females. However, AVP microinjection into the LS decreased the expression of conditioned place preference (CPP) to AMPH. Glutamate and GABA extracellular levels in the LS induced by AVP were studied in males and females. NAc GABA and DA extracellular levels induced by LS AVP microinjection in female rats were measured by microdialysis. In males, AVP perfusion produced a significant increase in LS GABA extracellular levels; however, a decrease in GABA extracellular levels was observed in females. Both in males and females, LS AVP perfusion did not produce changes in LS glutamate extracellular levels. Microinjection of AVP into the LS did not change GABA or DA extracellular levels in the NAc of females. Discussion: Therefore, AVP administration into the LS produces different LS-NAc neurochemical responses in females than males but decreases CPP to AMPH in both sexes. The behavioral response in males is due to a decrease in NAc DA levels, but in females, it could be due to a preventive increase in NAc DA levels. It is reasonable to postulate that, in females, the decrease in conditioning produced by AVP microinjection is influenced by other factors inherent to sex, and an effect on anxiety cannot be discarded.

Major depressive disorder (MDD) is associated with disruptions in glutamatergic and GABAergic activity in the medial prefrontal cortex (mPFC), leading to altered synaptic formation and function. Low doses of ketamine rapidly rescue these deficits, inducing fast and sustained antidepressant effects. While it is suggested that ketamine produces a rapid glutamatergic enhancement in the mPFC, the temporal dynamics and the involvement of GABA interneurons in its sustained effects remain unclear. Using simultaneous photometry recordings of calcium activity in mPFC pyramidal and GABA neurons, as well as chemogenetic approaches in Gad1-Cre mice, we explored the hypothesis that initial effects of ketamine on glutamate signaling trigger subsequent enhancement of GABAergic responses, contributing to its sustained antidepressant responses. Calcium recordings revealed a biphasic effect of ketamine on activity of mPFC GABA neurons, characterized by an initial transient decrease (phase 1, <30 min) followed by an increase (phase 2, >60 min), in parallel with a transient increase in excitation/inhibition levels (10 min) and lasting enhancement of glutamatergic activity (30-120 min). Previous administration of ketamine enhanced GABA neuron activity during the sucrose splash test (SUST) and novelty suppressed feeding test (NSFT), 24 h and 72 h post-treatment, respectively. Chemogenetic inhibition of GABA interneurons during the surge of GABAergic activity (phase 2), or immediately before the SUST or NSFT, occluded ketamine\'s behavioral actions. These results indicate that time-dependent modulation of GABAergic activity is required for the sustained antidepressant-like responses induced by ketamine, suggesting that approaches to enhance GABAergic plasticity and function are promising therapeutic targets for antidepressant development.

The neuronal excitotoxicity that follows reoxygenation after a hypoxic period may contribute to epilepsy, Alzheimer\'s disease, Parkinson\'s disease and various disorders that are related to inadequate supplement of oxygen in neurons. Therefore, counteracting the deleterious effects of post-hypoxic stress is an interesting strategy to treat a large spectrum of neurodegenerative diseases. Here, we show that the expression of the key telomere protecting protein Trf2 decreases in the brain of mice submitted to a post-hypoxic stress. Moreover, downregulating the expression of Terf2 in hippocampal neural cells of unchallenged mice triggers an excitotoxicity-like phenotype including glutamate overexpression and behavioral alterations while overexpressing Terf2 in hippocampal neural cells of mice subjected to a post-hypoxic treatment prevents brain damages. Moreover, Terf2 overexpression in culture neurons counteracts the oxidative stress triggered by glutamate. Finally, we provide evidence that the effect of Terf2 downregulation on excitotoxicity involves Sirt3 repression leading to mitochondrial dysfunction. We propose that increasing the level of Terf2 expression is a potential strategy to reduce post-hypoxic stress damages.

The symptoms of post-traumatic stress disorder (PTSD) include re-experiencing trauma, avoidance behaviors, negative alterations in cognition and mood. However, the underlying molecular mechanisms are unclear. Dysfunction of hypothalamic-pituitary-adrenal axis (HPA-axis) and dysregulation of glutamatergic and GABAergic systems were shown during PTSD. Therefore, regulating hormonal change or glutamate energy metabolism are considered as a therapeutic approach to alleviate this condition. Herbal medicine may be effective in treating PTSD due to its ability to target multiple underlying mechanisms with various compounds. Hominis placenta (HP) is a traditional medicine widely used in East Asia for various conditions. However, the effect on PTSD has not been clarified. We aimed to investigate the effects of HP treatment in single-prolonged stress with shock (SPSS)-induced PTSD mice and explore its possible mechanisms. HP treatment at ST36 acupoints, combined with herbal medicine and acupuncture point stimulation, was applied three times/week for 2 weeks. HP treatment effectively alleviated anxiety and cognitive decline in SPSS-induced PTSD mice, as detected by Open field and the Y-maze test. Additionally, HP decreased the corticosterone levels and proinflammatory cytokines in the serum, modulated brain energy metabolism, and inhibited glutamate excitotoxicity, while regulating neuronal activity through modulating brain-derived neurotrophic factor (BDNF) levels, as demonstrated by western blot and immunohistochemistry, and flow cytometry analyses. These findings reveal that HP treatment effectively alleviates PTSD-like behaviors by regulating energy metabolism and neuronal activity though modulation of the HPA-axis and BDNF levels in PTSD mice, indicating that HP treatment is a promising therapeutic approach for PTSD.

Cerebral function is linked to a high level of metabolic activity and relies on glucose as its primary energy source. Glucose aids in the maintenance of physiological brain activities; as a result, a disruption in metabolism has a significant impact on brain function, launching a chain of events that leads to neuronal death. This metabolic insufficiency has been observed in a variety of brain diseases and neuroexcitotoxicity disorders, including hepatic encephalopathy. It is a significant neurological complication that develops in people with liver disease, ranging from asymptomatic abnormalities to coma. Hyperammonemia is the main neurotoxic villain in the development of hepatic encephalopathy and induces a wide range of complications in the brain. The neurotoxic effects of ammonia on brain function are thought to be mediated by impaired glucose metabolism. Accordingly, in this review, we provide an understanding of deranged brain energy metabolism, emphasizing the role of glucose metabolic dysfunction in the pathogenesis of hepatic encephalopathy. We also highlighted the differential metabolic profiles of brain cells and the status of metabolic cooperation between them. The major metabolic pathways that have been explored are glycolysis, glycogen metabolism, lactate metabolism, the pentose phosphate pathway, and the Krebs cycle. Furthermore, the lack of efficacy in current hepatic encephalopathy treatment methods highlights the need to investigate potential therapeutic targets for hepatic encephalopathy, with regulating deficient bioenergetics being a viable alternative in this case. This review also demonstrates the importance of the development of glucose metabolism-focused disease diagnostics and treatments, which are now being pursued for many ailments.

Positron emission tomography (PET) and magnetic resonance spectroscopy (1H-MRS) are complementary techniques that can be applied to study how proteinopathy and neurometabolism relate to cognitive deficits in preclinical stages of Alzheimer\'s disease (AD)-mild cognitive impairment (MCI) and late-life depression (LLD). We acquired beta-amyloid (Aβ) PET and 7 T 1H-MRS measures of GABA, glutamate, glutathione, N-acetylaspartate, N-acetylaspartylglutamate, myo-inositol, choline, and lactate in the anterior and posterior cingulate cortices (ACC, PCC) in 13 MCI and 9 LLD patients, and 13 controls. We used linear regression to examine associations between metabolites, Aβ, and cognitive scores, and whether metabolites and Aβ explained cognitive scores better than Aβ alone. In the ACC, higher Aβ was associated with lower GABA in controls but not MCI or LLD patients, but results depended upon MRS data quality control criteria. Greater variance in California Verbal Learning Test scores was better explained by a model that combined ACC glutamate and Aβ deposition than by models that only included one of these variables. These findings identify preliminary associations between Aβ, neurometabolites, and cognition.