Striatum Regions Research Articles

Behavioural and electrophysiological features of WAG/Rij rats with different forms of genetic epilepsy

WAG/Rij rats are widely used as a genetic model of absence epilepsy. Approximately 15–50% rats of the strain are susceptible to audiogenic seizures. WAG/Rij rats demonstrate depressive-like behavior. After preliminary sound provocation an increased level of anxiety was found in audiogenic susceptible WAG/Rij subgroup. Electrophysiological and behavioral studies suggest the involvement of the dopaminergic system in both absence and audiogenic epilepsy. An increased binding density to dopamine receptors was found in the dorsal striatum subregions in audiogenic prone rats compared to non-audiogenic. The study aims were (1) to determine whether behavioral changes in WAG/Rij rats were genetically determined or induced by prior sound stimulation; (2) how regions of the dorsal striatum with different density of dopamine receptors in subpopulations of WAG/Rij rats are involved in the absence epilepsy control. The study was conducted using two rat groups: WAG/Rij-nonAGS (absence epilepsy) and WAG/Rij-AGS (mixed epilepsy). The study was performed using tests: “Elevated plus maze”, “Forced swimming” and “Three chamber sociability test”. High-frequency deep brain stimulation was performed for evaluation of dorsal striatum involvement in the absence seizure control. After experiments animals were tested for the susceptibility to audiogenic seizures. It demonstrated that the increased level of anxiety in WAG/Rij-AGS rats is genetically determined, while depressive-like behavior in WAG/Rij rats is not dependent on a predisposition to audiogenic seizures. Deviations in social behavior were observed in WAG/Rij-AGS rats. Stimulation of the dorsal striatum indicates differences in the control of absence and mixed forms of epilepsy in the

Endogenous Regulator of G protein Signaling 14 (RGS14) suppresses cocaine-induced emotionally motivated behaviors in female mice.

Addictive drugs hijack the neuronal mechanisms of learning and memory in motivation and emotion processing circuits to reinforce their own use. Regulator of G-protein Signaling 14 (RGS14) is a natural suppressor of post-synaptic plasticity underlying learning and memory in the hippocampus. The present study used immunofluorescence and RGS14 knockout mice to assess the role of RGS14 in behavioral plasticity and reward learning induced by chronic cocaine in emotional-motivational circuits. We report that RGS14 is strongly expressed in discrete regions of the ventral striatum and extended amygdala in wild-type mice, and is co-expressed with D1 and D2 dopamine receptors in neurons of the nucleus accumbens (NAc). Of note, we found that RGS14 is upregulated in the NAc in mice with chronic cocaine history following acute cocaine treatment. We found significantly increased cocaine-induced locomotor sensitization, as well as enhanced conditioned place preference and conditioned locomotor activity in RGS14-deficient mice compared to wild-type littermates. Together, these findings suggest that endogenous RGS14 suppresses cocaine-induced plasticity in emotional-motivational circuits, implicating RGS14 as a protective agent against the maladaptive neuroplastic changes that occur during addiction.

Hyperactivity and altered functional connectivity of the ventral striatum in schizophrenia compared with bipolar disorder: A resting state fMRI study

BackgroundSchizophrenia patients frequently present with structural and functional abnormalities of the ventral striatum (VS). Methodswe examined basal activation state and functional connectivity (FC) in four subregions of the bilateral ventral striatum: left inferior ventral striatum (VSi_L), left superior ventral striatum(VSs_L), right inferior ventral striatum(VSi_R), and right superior ventral striatum(VSs_R). Resting-state functional magnetic resonance images were obtained from 62 schizophrenia patients (SCH), 57 bipolar disorder (BD) patients, and 26 healthy controls (HCs). ResultsThe schizophrenia group exhibited greater fALFF in bilateral VS subregions compared to BD and HC groups as well as greater FC between the bilateral VSi and multiple brain regions, including the thalamus, putamen, posterior cingulate gyrus (PCC), frontal cortex and caudate. Moreover, the fALFF values of the bilateral ventral striatum were positively correlated with the severity of positive symptoms. We also found the functional connectivity between the bilateral inferior ventral striatum and some brain regions aforementioned were positively correlated with the severity of negative symptoms. ConclusionThese findings confirm a crucial contribution of ventral striatum dysfunction, especially of the bilateral VSi in schizophrenia. Functionally dissociated regions of the ventral striatum are differentially disturbed in schizophrenia.

Difference in Laterality of the Dorsal Striatum in Schizoaffective Disorder.

Recent research has demonstrated that the dorsal striatum is directly associated with the integration of cognitive, sensory-motor, and motivational/emotional data. Disruptions in the corticostriatal circuit have been implicated in the pathophysiology of psychosis. The dorsal striatum was reported to show lateralized pathology in psychotic disorders. In this study, we aimed to analyze the laterality of the dorsal striatum with texture analysis of T2-weighted magnetic resonance imaging (MRI) images from schizoaffective disorder (SAD) patients. Twenty SAD patients, met the inclusion criteria and had available cranial MRI data were assigned as the patient group. Twenty healthy individuals were determined as the control group. Texture analysis values were obtained from striatum region of interests (ROI) generated from T2-weighted MRI images. Data are presented as mean and standard deviation. The suitability of the data for normal distribution was analyzed with the Kolmogorov-Smirnov test. Analysis of variance (ANOVA) test (Post Hoc TUKEY) was employed to compare the group data based on test findings. There was no significant difference between the groups in terms of gender and age. There were differences in the values of texture analysis parameters of both caudate and putamen nuclei in comparison to controls. We identified differences in the left dorsal striatum nuclei in SAD. The differences in the putamen were more and more pronounced than in the caudate. Texture analyses suggest that the left dorsal striatum nuclei may be different in SAD patients. Further studies are needed to determine the pathophysiology of SAD and how it may affect disease treatment.

Accelerating multipool CEST MRI of Parkinson's disease using deep learning-based Z-spectral compressed sensing.

To develop a deep learning-based approach to reduce the scan time of multipool CEST MRI for Parkinson's disease (PD) while maintaining sufficient prediction accuracy. A deep learning approach based on a modified one-dimensional U-Net, termed Z-spectral compressed sensing (CS), was proposed to recover dense Z-spectra from sparse ones. The neural network was trained using simulated Z-spectra generated by the Bloch equation with various parameter settings. Its feasibility and effectiveness were validated through numerical simulations and in vivo rat brain experiments, compared with commonly used linear, pchip, and Lorentzian interpolation methods. The proposed method was applied to detect metabolism-related changes in the 6-hydroxydopamine PD model with multipool CEST MRI, including APT, CEST@2 ppm, nuclear Overhauser enhancement, direct saturation, and magnetization transfer, and the prediction performance was evaluated by area under the curve. The numerical simulations and in vivo rat-brain experiments demonstrated that the proposed method could yield superior fidelity in retrieving dense Z-spectra compared with existing methods. Significant differences were observed in APT, CEST@2 ppm, nuclear Overhauser enhancement, and direct saturation between the striatum regions of wild-type and PD models, whereas magnetization transfer exhibited no significant difference. Receiver operating characteristic analysis demonstrated that multipool CEST achieved better predictive performance compared with individual pools. Combined with Z-spectral CS, the scan time of multipool CEST MRI can be reduced to 33% without distinctly compromising prediction accuracy. The integration of Z-spectral CS with multipool CEST MRI can enhance the prediction accuracy of PD and maintain the scan time within a reasonable range.

Disruption of neural periodicity predicts clinical response after deep brain stimulation for obsessive-compulsive disorder

Recent advances in surgical neuromodulation have enabled chronic and continuous intracranial monitoring during everyday life. We used this opportunity to identify neural predictors of clinical state in 12 individuals with treatment-resistant obsessive-compulsive disorder (OCD) receiving deep brain stimulation (DBS) therapy (NCT05915741). We developed our neurobehavioral models based on continuous neural recordings in the region of the ventral striatum in an initial cohort of five patients and tested and validated them in a held-out cohort of seven additional patients. Before DBS activation, in the most symptomatic state, theta/alpha (9 Hz) power evidenced a prominent circadian pattern and a high degree of predictability. In patients with persistent symptoms (non-responders), predictability of the neural data remained consistently high. On the other hand, in patients who improved symptomatically (responders), predictability of the neural data was significantly diminished. This neural feature accurately classified clinical status even in patients with limited duration recordings, indicating generalizability that could facilitate therapeutic decision-making.

Developmental differences in striatal recruitment by reward prospects as a function of attentional demand

Adolescent risk-taking has been attributed to earlier-developing motivational neurocircuitry that is poorly controlled by immature executive-control neurocircuitry. Functional magnetic resonance imaging findings of increased ventral striatum (VS) recruitment by reward prospects in adolescents compared to adults support this theory. Other studies found blunted VS recruitment by reward-predictive cues in adolescents compared to adults. Task features may explain this discrepancy but have never been systematically explored. Adolescents and adults performed a novel reward task that holds constant the expected value of all rewards but varies whether rewards are dependent on vigilance-intensive responding versus making a lucky choice during a relaxed response window. We examined group by sub-task contrast differences in activation of VS and more motoric regions of striatum in response to anticipatory cues. Reward anticipation in both task conditions activated portions of striatum in both groups. In voxel-wise comparison, adults showed greater anticipatory recruitment of VS in trials involving choice during a relaxed time window, not in the more vigilance-demanding trials as hypothesized. In accord with our hypotheses, however, adults showed greater activation in dorsal striatum and putamen volumes of interest during reward anticipation under vigilance-demanding conditions. Following trial outcome notifications, adolescents showed greater activation of the VS during reward notification but lower activation during loss notification. These data extend findings of cross-sectional age-group differences in incentive-anticipatory recruitment of striatum, by demonstrating in adults relatively greater recruitment of motor effector regions of striatum by attentional and motor demands.

Corticotropin releasing factor alters the functional diversity of accumbal cholinergic interneurons.

Cholinergic interneurons (ChIs) provide the main source of acetylcholine in the striatum and have emerged as a critical modulator of behavioral flexibility, motivation, and associative learning. In the dorsal striatum (DS), ChIs display heterogeneous firing patterns. Here, we investigated the spontaneous firing patterns of ChIs in the nucleus accumbens (NAc) shell, a region of the ventral striatum. We identified four distinct ChI firing signatures: regular single-spiking, irregular single-spiking, rhythmic bursting, and a mixed-mode pattern composed of bursting activity and regular single spiking. ChIs from females had lower firing rates compared with males and had both a higher proportion of mixed-mode firing patterns and a lower proportion of regular single-spiking neurons compared with males. We further observed that across the estrous cycle, the diestrus phase was characterized by higher proportions of irregular ChI firing patterns compared with other phases. Using pooled data from males and females, we examined how the stress-associated neuropeptide corticotropin releasing factor (CRF) impacts these firing patterns. ChI firing patterns showed differential sensitivity to CRF. This translated into differential ChI sensitivity to CRF across the estrous cycle. Furthermore, CRF shifted the proportion of ChI firing patterns toward more regular spiking activity over bursting patterns. Finally, we found that repeated stressor exposure altered ChI firing patterns and sensitivity to CRF in the NAc core, but not the NAc shell. These findings highlight the heterogeneous nature of ChI firing patterns, which may have implications for accumbal-dependent motivated behaviors.NEW & NOTEWORTHY Cholinergic interneurons (ChIs) within the dorsal and ventral striatum can exert a major influence on network output and motivated behaviors. However, the firing patterns and neuromodulation of ChIs within the ventral striatum, specifically the nucleus accumbens (NAc) shell, are understudied. Here, we report that NAc shell ChIs have heterogeneous ChI firing patterns that are labile and can be modulated by the stress-linked neuropeptide corticotropin releasing factor (CRF) and by the estrous cycle.

Quercetin's Restorative Properties in Male Mice with 3-Nitropropionic Acid-induced Huntington-like Symptoms: Molecular Docking, Behavioral, and Biochemical Assessment.

The neurotoxicity of 3-Nitropropionic acid (3-NP) is well known. Herein, the prophylactic versus therapeutic effects of quercetin (QCT) were investigated against 3-NP-induced behavioral anomalies and oxidative neural damage. Thirty male mice were assigned into five groups; the negative control group, the QCT group (25 mg/kg/day, p.o. for 21 days), the 3-NP group (17 days), the prophylactic group (QCT administration for 14 consecutive days, and then 3-NP was administrated), the therapeutic group (3-NP was administrated and then QCT for 21 days). At the end of the animal treatment, behavioral studies were assessed. Subsequently, the brain sample tissues were assessed for oxidative stress-related parameters and histological evaluation. Moreover, the potential interaction between 3-NP and tumor necrosis factor-alpha (TNF-α) was evaluated by using a molecular docking study. 3-NP markedly led to neurotoxicity which was indicated by behavioral deficits (motor behavior, depression-like behavior, memory dysfunction, and passive avoidance) and oxidative damage. Blind and targeted molecular docking results showed good interaction between 3-NP and TNF-α. However, the prophylactic effects of QCT were superior to the therapeutic effects for attenuating 3-NP-induced neurobehavioral and oxidative neural changes in experimental mice, which histological changes of the brain's striatum region approved our findings. Taken together, the antioxidant activity of QCT remarkably could attenuate 3-NP-induced neurobehavioral deficits and mitochondrial dysfunctions in mice.

Feature engineering-based analysis of DaTSCAN-SPECT imaging-derived features in the detection of SWEDD and Parkinson's disease

Scans without evidence of dopamine deficit (SWEDD) refer to patients with a normal dopamine transporter scan who have been clinically considered to have Parkinson's disease (PD). To prevent misdiagnosis between SWEDD and PD, it is imperative to identify the manifestations of SWEDD in the early stages. In this experiment, imaging-based striatum binding ratio (SBR) features of four striatum regions are utilized and obtained from the Parkinson's Progression Marker Initiative (PPMI). After that, by implementing feature engineering, six combinational pairs are created by taking two SBR features at a time using a mathematical-based combination (nCr)technique. Then, by evaluating the maximum and minimum values of features of each pair, the six new features are obtained from each combinational pair based on arithmetic operations. Finally, a total of thirty-six new features have been derived by using these existing four SBR features. These derived 36 features are further applied to various supervised and ensemble classifiers of machine learning for three binary classifications (PD vs SWEDD, PD vs healthy, and healthy vs SWEDD). From the consequences, it has been observed that the Naive Bayes classifier performed well across all classification probabilities and among other classifiers. To differentiate SWEDD from PD, the classifier achieved 98.03 % accuracy, 98.85 % recall, 96.29 % precision, 92.96 % Jaccard_score, 96.29 % F1-score, & 99.34 % AUC. Moreover, the comparison has been made between with and without implementing the feature engineering technique for all three classification probabilities for better interpretation. Thus, it is reasonable to hypothesize that the suggested method, which is based on feature engineering, may not only improve performance but also help medical professionals diagnose diseases at early stages.

Unraveling the complex pathophysiology of white matter hemorrhage in intracerebral stroke: A single-cell RNA sequencing approach.

This study aims to elucidate the cellular dynamics and pathophysiology of white matter hemorrhage (WMH) in intracerebral hemorrhage (ICH). Using varying doses of collagenase IV, a consistent rat ICH model characterized by pronounced WMH was established. Verification was achieved through behavioral assays, hematoma volume, and histological evaluations. Single-cell suspensions from the hemorrhaged region of the ipsilateral striatum on day three post-ICH were profiled using single-cell RNA sequencing (scRNA-seq). Gene Ontology (GO) and gene set variation analysis (GSVA) further interpreted the differentially expressed genes (DEGs). Following WMH induction, there was a notable increase in the percentage of myeloid cells and oligodendrocyte precursor cells (OPCs), alongside a reduction in the percentage of neurons, microglia, and oligodendrocytes (OLGs). Post-ICH WMH showed homeostatic microglia transitioning into pro-, anti-inflammatory, and proliferative states, influencing lipid metabolic pathways. Myeloid cells amplified chemokine expression, linked with ferroptosis pathways. Macrophages exhibited M1 and M2 phenotypes, and post-WMH, macrophages displayed a predominance of M2 phenotypes, characterized by their anti-inflammatory properties. A surge in OPC proliferation aligned with enhanced ribosomal signaling, suggesting potential reparative responses post-WMH. The study offers valuable insights into WMH's complex pathophysiology following ICH, highlighting the significance and utility of scRNA-seq in understanding the cellular dynamics and contributing to future cerebrovascular research.

A cell therapy approach based on iPSC-derived midbrain organoids for the restoration of motor function in a Parkinson’s disease mouse model

Parkinson's disease (PD) is a neurodegenerative disease characterized by the degeneration of dopaminergic (DA) neurons in the substantia nigra and loss of DA transmission in the striatum, thus making cell transplantation an effective treatment strategy. Here, we develop a cellular therapy based on induced pluripotent stem cell (iPSC)-derived midbrain organoids. By transplanting midbrain organoid cells into the striatum region of a 6-OHDA-lesioned PD mouse model, we found that the transplanted cells survived and highly efficiently differentiated into DA neurons. Further, using a dopamine sensor, we observed that the differentiated human DA neurons could efficiently release dopamine and were integrated into the neural network of the PD mice. Moreover, starting from four weeks after transplantation, the motor function of the transplanted mice could be significantly improved. Therefore, cell therapy based on iPSC-derived midbrain organoids can be a potential strategy for the clinical treatment of PD.

Ventromedial Prefrontal Cortex and Ventral Striatum Volumes in Patients with Alcohol Use Disorder

ABSTRACT The ventromedial prefrontal cortex (vmPFC) and the ventral striatum are brain regions that are critical for the reward circuit and the maintenance of pleasure. The relationship between these regions and alcohol use disorder has been investigated in the literature in a variety of ways. In this context, it is aimed to determine whether there are structural changes in the vmPFC and ventral striatum regions in patients with alcohol use disorder (AUD) compared to healthy control subjects. Fifteen patients with AUD according to the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM 5) diagnostic criteria and seventeen healthy controls participated in our study. The volumes of the vmPFC and ventral striatum were measured in subjects. The mean volumes of both sides of the vmPFC were significantly smaller in patients with AUD than those in the healthy control group whereas both sides of ventral striatum volumes were larger. This study is one of the few to examine structural changes in the vmPFC and ventral striatum together in patients with ACD. Although the contribution of the positive findings to the literature is important, more comprehensive studies are needed to strengthen the existing findings.

Tonabersat Significantly Reduces Disease Progression in an Experimental Mouse Model of Multiple Sclerosis.

Multiple sclerosis (MS) is a neurodegenerative disease marked by chronic neuroinflammation thought to be mediated by the inflammasome pathway. Connexin 43 (Cx43) hemichannels contribute to the activation of the inflammasome through the release of adenosine triphosphate (ATP) inflammasome activation signals. The objective of the study was to evaluate if the Cx43 hemichannel blocker, tonabersat, is effective in modulating the inflammatory response and reducing disability in the myelin oligodendrocyte glycoprotein 35-55-induced experimental autoimmune encephalomyelitis (MOG35-55 EAE) model of MS. Here, we show that the Cx43 hemichannel blocking drug, tonabersat, significantly reduced expression of neuroinflammatory markers for microglial activation (ionized calcium-binding adapter molecule 1 (Iba1)) and astrogliosis (glial fibrillary acidic protein (GFAP)) while preserving myelin basic protein (MBP) expression levels in the corpus callosum, motor cortex, and striatum regions of the brain in MOG35-55 EAE mice. Reduced NOD-like receptor protein 3 (NLRP3) inflammasome complex assembly and Caspase-1 activation confirmed the drug's mode of action. MOG35-55 EAE mice showed clinical signs of MS, but MOG35-55 EAE mice treated with tonabersat retained behavior closer to normal. These data suggest that clinical trial phase IIb-ready tonabersat may merit further investigation as a promising candidate for MS treatment.

Hemispheric coupling between structural and functional asymmetries in clinically asymptomatic carotid stenosis with cognitive impairment.

Advanced carotid stenosis is a known risk factor for ischemic stroke and vascular dementia, and it is associated with multidomain cognitive impairment as well as asymmetric alterations in hemispheric structure and function. Here we introduced a novel measure-the asymmetry index of amplitude of low-frequency fluctuations (ALFF_AI)-derived from resting-state functional magnetic resonance imaging. This measure captures the hemispheric asymmetry of intrinsic brain activity using high-dimensional registration. We aimed to investigate functional brain asymmetric alterations in patients with severe asymptomatic carotid stenosis (SACS). Furthermore, we extended the analyses of ALFF_AI to different frequencies to detect frequency-specific alterations. Finally, we examined the coupling between hemispheric asymmetric structure and function and the relationship between these results and cognitive tests, as well as the white matter hyperintensity burden. SACS patients presented significantly decreased ALFF_AI in several clusters, including the visual, auditory, parahippocampal, Rolandic, and superior parietal regions. At low frequencies (0.01-0.25Hz), the ALFF_AI exhibited prominent group differences as frequency increased. Further structure-function coupling analysis indicated that SACS patients had lower coupling in the lateral prefrontal, superior medial frontal, middle temporal, superior parietal, and striatum regions but higher coupling in the lateral occipital regions. These findings suggest that, under potential hemodynamic burden, SACS patients demonstrate asymmetric hemispheric configurations of intrinsic activity patterns and a decoupling between structural and functional asymmetries.

A Pilot Study of the Striatal Dopamine Transporter Levels in Kratom-Dependent and Normal Subjects Using 99mTc-TRODAT-1 Single Photon Emission Computed Tomography-Computed Tomography (SPECT-CT).

The study aims to elucidate the effects of kratom addiction on dopamine transporter (DAT) using[2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiolato(3-)-N2,N20,S2,S20]oxo-[1R-(exo-exo)]-[99mTc] technetium (99mTc-TRODAT-1) brain single photon emission computed tomography-computed tomography (SPECT-CT) in kratom-dependent and healthy subjects. We recruited 12 kratom-dependent subjects and 13 healthy men to participate in this study. Addiction, craving, depression, and cognitive scores were assessed. All subjects received a single bolus injection of 99mTc-TRODAT-1 with 914.1 MBq ± 65.5 of activity (mean ± SD). The brain SPECT-CT images were reconstructed using 3D ordered subset expectation maximization (3D-OSEM) along with attenuation correction (AC), scatter correction (SC), and resolution recovery (RR) with an iteration number of four and a subset of 10. The Cohen's Kappa interrater-reliability between two raters, the standardized uptake value of body weight (SUVBW), and the asymmetrical index percentage (AI%) were evaluated. Kappa statistics showed a fine agreement of abnormal 99mTc-TRODAT-1 uptake in the striatum region for the kratom-dependent group with the κ value of 0.69 (p = 0.0001), and the percentage of agreement for rater 1 and rater 2 was 56% and 64%, respectively. There was a reduction in average SUV in kratom-dependent subjects compared to healthy control subjects in the left caudate and left striatum (0.938 vs. 1.251, p = 0.014, and 1.055 vs. 1.29, p = 0.036, respectively). There was a significant difference in the AI% of the caudate region between the kratom-dependent group and the normal group (33% vs. 14%, p = 0.019). Our findings signify that kratom addiction, may cause a change in DAT level and the results can be confirmed using 99mTc-TRODAT-1 SPECT-CT.

Perturbed neurochemical and microstructural organization in a mouse model of prenatal opioid exposure: A multi-modal magnetic resonance study.

Methadone-based treatment for pregnant women with opioid use disorder is quite prevalent in the clinical environment. A number of clinical and animal model-based studies have reported cognitive deficits in infants prenatally exposed to methadone-based opioid treatments. However, the long-term impact of prenatal opioid exposure (POE) on pathophysiological mechanisms that govern neurodevelopmental impairment is not well understood. Using a translationally relevant mouse model of prenatal methadone exposure (PME), the aim of this study is to investigate the role of cerebral biochemistry and its possible association with regional microstructural organization in PME offspring. To understand these effects, 8-week-old male offspring with PME (n = 7) and prenatal saline exposure (PSE) (n = 7) were scanned in vivo on 9.4 Tesla small animal scanner. Single voxel proton magnetic resonance spectroscopy (1H-MRS) was performed in the right dorsal striatum (RDS) region using a short echo time (TE) Stimulated Echo Acquisition Method (STEAM) sequence. Neurometabolite spectra from the RDS was first corrected for tissue T1 relaxation and then absolute quantification was performed using the unsuppressed water spectra. High-resolution in vivo diffusion MRI (dMRI) for region of interest (ROI) based microstructural quantification was also performed using a multi-shell dMRI sequence. Cerebral microstructure was characterized using diffusion tensor imaging (DTI) and Bingham-neurite orientation dispersion and density imaging (Bingham-NODDI). MRS results in the RDS showed significant decrease in N-acetyl aspartate (NAA), taurine (tau), glutathione (GSH), total creatine (tCr) and glutamate (Glu) concentration levels in PME, compared to PSE group. In the same RDS region, mean orientation dispersion index (ODI) and intracellular volume fraction (VFIC) demonstrated positive associations with tCr in PME group. ODI also exhibited significant positive association with Glu levels in PME offspring. Significant reduction in major neurotransmitter metabolites and energy metabolism along with strong association between the neurometabolites and perturbed regional microstructural complexity suggest a possible impaired neuroadaptation trajectory in PME offspring which could be persistent even into late adolescence and early adulthood.

Low-moderate dose whole-brain γ-ray irradiation modulates the expressions of glial fibrillary acidic protein and intercellular adhesion molecule-1 in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine–induced Parkinson’s disease mouse model

The anti-inflammatory efficacy of radiation therapy (RT) with single fractions below 1.0 Gy has been demonstrated in Alzheimer’s disease mouse models. As neuroinflammation is also a major pathological feature of Parkinson’s disease (PD), RT may also be effective in PD treatment. Therefore, this study aimed to investigate the anti-inflammatory effect of low-moderate dose RT (LMDRT, 0.6 Gy/single dose, for 5 days) exposure in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 30 mg/kg, intraperitoneally, for 5 consecutive days)-induced PD mouse model. Importantly, LMDRT reduced the levels of glial fibrillary acidic protein and intercellular adhesion molecule-1 (CD54) in the striatum region, which increased following MPTP administration. LMDRT also modulated inflammatory gene expression patterns in the substantia nigra region of the MPTP-treated mice. However, LMDRT had no direct effects on the severe loss of dopaminergic neurons and impaired motor behavior in the rotarod test. These results indicate that LMDRT has anti-inflammatory effects by modulating neuroinflammatory factors, including glial fibrillary acidic protein and intercellular adhesion molecule-1, but showed no behavioral improvements or neuroprotection in the MPTP-induced mouse model of PD.

Targeted Energy Metabolomics Combined with Spatial Metabolomics Study on the Efficacy of Guhong Injection Against Cerebral Ischemia Reperfusion.

Optimizing the metabolic phenotype to improve cerebral function is critical for treatment of cerebral ischemia-reperfusion (I/R) injury. Guhong injection (GHI), which comprised safflower extract and aceglutamide, is widely prescribed in Chinese medicine for the treatment of cerebrovascular diseases. In this study, a combination of LC-QQQ-MS and MALDI-MSI were utilized to explore tissue-specific metabolic alterations in the brain of I/R, as well as to evaluate the therapeutic effect of GHI. Pharmacological evaluation demonstrated that GHI can significantly improve infarction rate, neurological deficit, cerebral blood flow, and neuronal damage in I/R rats. Based on LC-QQQ-MS, 23 energy metabolites were found to be significantly altered in the I/R group compared to the sham group (P < 0.05). After GHI treatment, 12 metabolites, including G6P, TPP, NAD, citrate, succinate, malate, ATP, GTP, GDP, ADP, NADP, and FMN showed a significant tendency of returning to baseline values (P < 0.05). Based on MALDI-MSI, 4 metabolites in glycolysis and TCA, 4 metabolites in nucleic acid metabolism, 4 amino acid metabolites, and 6 metabolites were discovered and compared between the different groups in the four special regions of cortex, hippocampus, hypothalamus, and striatum. Parts of these were found to have significant changes after I/R in the special brain region, and were regulated by GHI. The study provides comprehensive and detailed information for specific metabolic reprogramming of brain tissue in rats with I/R, and the therapeutic effect of GHI. Schema describing the discovery strategies of integrated LC-MS and MALDI-MSI to identify cerebral ischemia reperfusion metabolic reprogramming and GHI therapeutic effects.

The prediction of market-level food choices by the neural valuation signal.

Neuroimaging studies have demonstrated the ability to use the brain activity of a group of individuals to forecast the behavior of an independent group. In the current study, we attempted to forecast aggregate choices in a popular restaurant chain. During our functional magnetic resonance imaging (fMRI) study, 22 participants were exposed to 78 photos of dishes from a new menu of a popular restaurant chain. In addition to self-reported preferences, fMRI data was extracted from an a priori domain-general and task-specific region of interest-the ventral striatum. We investigated the relationship between the neural activity and real one-year sales provided by the restaurant chain. Activity in the ventral striatum, which was defined using the task-specific region of interest, significantly correlated (r = 0.28, p = 0.01) with one-year sales. A regression analysis, which included ventral striatum activity together with the objective characteristics of the products (price and weight), behavioral, and survey data, showed R2 values of 0.33. Overall, our results confirm prior studies, which have suggested, that brain activity in the reward system of a relatively small number of individuals can forecast the aggregate choice of a larger independent group of people.