Translational Neuroscience最新文献

Objective: This study aims to determine if Lycium barbarum polysaccharides (LBP) extract attenuate oxidative stress by regulating the SIRT1/PGC-1α axis, potentially ameliorating oxygen-glucose deprivation/reperfusion (OGD/R)-induced neuronal damage.

Methods: A cellular hypoxia/reoxygenation model (OGD/R) using HT22 cells was established to simulate cerebral ischemia-reperfusion injury. Cells were allocated into four groups: normal (Control), hypoxia (OGD/R), LBP extract-treated (OGD/R + LBP at 25, 50, 100 μg/mL), and SIRT1-inhibited (OGD/R + S100). Western blot and qPCR were performed to detect the expression of pathway-related factors, oxidative stress, mitochondrial function, and apoptosis-related factors.

Results: Compared to the Control group, the OGD/R group exhibited significantly reduced cell survival, increased LDH release, apoptosis rate, and reactive oxygen species (ROS) levels. After intervention with LBP extract, cell survival increased, LDH release, ROS levels, and apoptosis rates reduced. The above injuries were associated with the inhibition of the SIRT1/PGC-1α pathway. LBP extract can attenuate the hypoxia-reperfusion-induced inhibition of the SIRT1/PGC-1α pathway and reverse the resulting high levels of oxidative stress and apoptosis, ultimately ameliorating cellular injury.

Conclusion: LBP extract's protective effects against ischemia-reperfusion injury in HT22 cells appear linked to the modulation of the SIRT1/PGC-1α pathway and a reduction in oxidative stress.

Background: Depression is a pervasive neuropsychiatric disorder having significant social and economic impacts and often linked to imbalances in neurotransmitter systems. Traditional herbal medicines have garnered attention for their potential antidepressant effects, with limited research on Helianthus annuus (sunflower) as a therapeutic option.

Objectives: The present study was carried out to investigate the anti-depressant and neuromodulatory potential of hydroalcoholic extract of Helianthus annuus (H. annuus) florets in mouse models of depression.

Methods: Depression was induced in rats by the forced swim test (FST) and tail suspension test (TST). The hydroalcoholic extract of H. annuus was used as the test drug given in the doses of 200 and 400 mg/kg, whereas fluoxetine was used as the standard drug.

Results: The results revealed that the H. annuus extract decreased the immobility time significantly as reflected in FST and TST. Treatment with H. annuus extract also demonstrated significant improvement in the swimming and climbing times as reflected in FST. Administration of H. annuus extract significantly improved neurotransmitter levels such as serotonin, dopamine, and norepinephrine, which were significantly lowered in depression control rats. The mean value of thiobarbituric acid reactive substances was significantly lowered after the administration of H. annuus extract. Additionally, the levels of glutathione, superoxide dismutase, and catalase were significantly increased after the administration of H. annuus extract. Additionally, the mean value of inflammatory cytokines, for example, tumour necrosis factor alpha and interleukin-6 were reduced significantly in groups treated with H. annuus extract.

Conclusions: The results suggest that H. annuus extract exhibited significant antidepressant and neuromodulatory potential by ameliorating behavioural parameters, oxidative stress, and inflammatory markers.

Estradiol shapes systemic glucose homeostasis by action on ventromedial hypothalamic nucleus (VMN) targets. The neuropeptide transmitter growth hormone-releasing hormone (Ghrh) governs counterregulatory neurochemical marker mRNA expression in dorsomedial VMN (VMNdm) Ghrh/steroidogenic factor-1 (SF-1/Nr5a1) neurons. The current research used tools for in vivo gene silencing and single-cell laser catapult microdissection/multiplex qPCR to determine if VMN Ghrh receptor (Ghrh-R) regulates nuclear and/or membrane estrogen receptor (ER) gene transcription in those neurons. Intra-VMN Ghrh-R siRNA correspondingly up- or down-regulated baseline VMNdm Ghrh/SF-1 neuron ER-alpha (ERα) or G protein-coupled estrogen receptor-1 (GPER) transcripts in male rats; neither mRNA was affected by gene silencing in females. In each sex, hypoglycemic repression of these ER gene profiles was averted by Ghrh-R gene knockdown. Both sexes exhibited diminished baseline VMNdm Ghrh/SF-1 neuron ER-beta (ERβ) gene expression following Ghrh-R gene knockdown. ERβ mRNA was diminished (male) or unaffected (female) by hypoglycemia; Ghrh-R siRNA pretreatment enhanced transcript levels in hypoglycemic rats of either sex. Aromatase gene expression is higher in male versus female VMNdm Ghrh/SF-1 neurons and is inhibited by hypoglycemia in male rats alone. Ghrh-R gene knockdown augmented aromatase mRNA levels in each sex irrespective of glucose status. Results document glucose-dependent Ghrh-R control of VMNdm Ghrh/SF-1 neuron ERα (female), ERβ (both sexes), and GPER (both sexes) gene expression. Ongoing studies aim to characterize mechanisms that cause a hypoglycemia-associated gain of regulatory control or switch in direction (stimulatory-to-inhibitory) of control. Outcomes identify VMNdm Ghrh/SF-1 neurons as a putative neuroestradiol source in each sex and implicate Ghrh-R in hypoglycemic repression of this neurosteroid profile in males.

Parkinson's disease (PD) is increasingly understood as a neurodegenerative condition whose pathology extends beyond the direct and indirect basal ganglia pathways. Clinically, patients are all too painfully aware of dysfunction not only of motor circuits but also of somatosensory, autonomic, cognitive, and emotional systems. Functional neuroimaging studies have begun to document a functional reorganization in the PD brain across a wide number of networks. In particular, the cerebellar-thalamocortical, as well as the fronto-striatal circuit, have been shown to undergo functional reorganization. In this narrative review, citing preclinical as well as clinical neuroimaging studies, our objective is to highlight trends and discuss the relevance of cerebral adaptive changes. It remains clear that not all changes contribute to the normalization of functions. Parsing differences between functional "compensation," "silencing," or "maladaptation" in neural circuits is important. A necessary next step in neurorehabilitation is the question of whether compensatory cerebral changes can be enhanced. In this regard, physical exercise remains of interest, given that in patients, exercise may allow some degree of symptom improvement and possibly slow the course of the disease. Future interventions may wish to integrate neuroimaging findings as potential targets to support neuroplastic changes.

Prosociality is a behavior characterized by actions performed for the benefit or well-being of others. Recent studies have corroborated parallels in brain activation patterns between rodents and humans during prosocial behaviors. These findings have the potential to advance our understanding of social impairments observed in neurodevelopmental disorders, brain injuries, neurological conditions, and mental health disorders. However, a consensus regarding prosocial paradigms in rodents remains scattered. This conceptual framework aims to (1) reframe prosociality as a set of complex behaviors emerging in response to environmental determinants that cannot be reduced to a single set of data; (2) highlight important methodological considerations, mediating variables, and behavioral analyses that influence prosocial behaviors; and (3) present a decision tree as a dynamic element within this conceptual framework to offer guidance to researchers. The conceptual framework and decision tree are concise and straightforward, providing a robust foundation for the ongoing utilization of current models and the creation of novel paradigms. The integration of this conceptual framework into research practices will contribute to the advancement of knowledge in the field of rodent prosociality and foster greater confidence in the validity and reproducibility of study findings.

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system characterized by neuroinflammation and progressive neurodegeneration. Growing evidence suggests that dietary interventions may influence MS progression and symptom management by modulating inflammation, oxidative stress, and gut microbiota composition. This narrative review examines the effects of the Mediterranean, plant-based, ketogenic, Wahls, Swank, intermittent fasting, and gluten-free diets, alongside key nutrients such as omega-3 fatty acids, vitamin D, polyphenols, and antioxidants. Among these, Mediterranean and plant-based diets have shown the most consistent benefits, including reductions in fatigue, improved quality of life, and modulation of inflammatory markers. The Wahls and Swank diets show promise but are primarily supported by studies from their respective research groups, raising concerns about long-term adherence and nutritional adequacy. The ketogenic diet and intermittent fasting have yielded mixed findings, with some studies suggesting benefits for fatigue and neuroprotection, while others highlight potential metabolic risks. The gluten-free diet and omega-3 supplementation lack robust evidence, with inconsistent findings across studies. Additionally, ultra-processed foods and diets high in saturated fats have been associated with increased inflammation and greater MS severity. Despite promising findings, limitations such as small sample sizes, short follow-up durations, and study design inconsistencies prevent definitive conclusions. Future research should prioritize large-scale, long-term randomized controlled trials to establish the efficacy, safety, and sustainability of dietary interventions in MS management. Mechanistic studies and standardized dietary protocols are also needed to better understand the role of diet in MS progression and symptom control.

Background: Several findings indicate that stress may influence epileptiform discharges manifesting in temporal-limbic areas, which may become a potential trigger of psychosis that may manifest without neurologically diagnosed epilepsy. Some findings suggest that measures assessing levels of inter-hemispheric information connection may reveal the spread of subclinical epileptiform neural activity associated with psychotic and seizure-like symptoms. Recent research also suggests that electrodermal activity (EDA), which is related to limbic activations, may allow indirect measurement of interhemispheric information transmission. These findings about the interhemispheric spread of information suggest a hypothesis that heightened spread of information between the brain hemispheres might indirectly indicate epileptiform discharges spreading between hemispheres.

Methods: We have analyzed and measured EDA and also cognitive and affective epileptic-like symptoms (CPSI, complex partial seizure-like symptoms), symptoms of chronic stress (Trauma Symptoms Checklist-40, TSC-40), and psychotic symptoms in 31 schizophrenia patients and compared these data with 31 healthy controls.

Results: The results indicate that in schizophrenia patients, the values of pointwise transinformation (PTI) calculated from right and left EDA time series are related to CPSI symptoms (Spearman correlation between CPSI and PTI is R = 0.48; p < 0.01) and symptoms of chronic stress (Spearman correlation between TSC-40 and PTI is R = 0.37, p < 0.05); both during mild stress conditions caused by conflicting (incongruent) Stroop task.

Conclusion: The analysis indicates potentially diagnostically useful results suggesting that heightened PTI values may reflect autonomic activations that hypothetically might be linked to higher interhemispheric transmission related to spreading of epileptiform discharges between hemispheres.

Background: Within the last few decades, the domestic pig has emerged as an advantageous biomedical animal model due to a vast number of similarities in realms of development and neuroanatomical features. Even so, a major challenge remains in how to translate time between the pig and human. Previously, researchers have developed a Translating Mammalian Time model that estimates the timing of 95 neurodevelopmental events across 9 mammalian species. By identifying the timing of these various events, one can include an additional animal into the model and assign a unique species score to predict the post-conception day (PCD) that other events will occur.

Objective: Our objective was to conduct a comprehensive literature review of pig neurodevelopmental events to enable chronological comparison to other mammalian species, including humans.

Methods: A total of 30 neurodevelopmental events with corresponding PCDs were identified, that were then used to optimize the pig's species score using grid search and gradient descent approaches.

Results and conclusion: Across both methods, the same species score of 2.157 was derived with a residual sum of squares of 4260.46. This species score places the domestic pig between the cat (1.808) and the macaque (2.255), thereby reinforcing the translational power of the pig comparable to non-human primates.

Background: Unruptured intracranial aneurysms (IAs) are increasingly detected due to advancements in neuroimaging. Despite improvements in treatment, aneurysmal subarachnoid haemorrhage (aSAH) is associated with high mortality and morbidity. Treatment decisions for IA are complex and individualized, considering aneurysm and patient-related risk factors. Genetic factors, particularly endothelial nitric oxide synthase (eNOS) polymorphisms, have been implicated in IA formation and rupture risk.

Methods: This study investigated the association between three eNOS polymorphisms (27-bp-VNTR, T786C, and G894T) and aSAH in a cohort of 275 patients with unruptured IA or aSAH. Patients were followed for at least 8 years with clinical and imaging assessments. Genotyping of selected polymorphisms was performed, and statistical analyses were conducted to identify interactions between genetic polymorphisms and established risk factors.

Results: A significant difference in the frequencies of genotypes and allele carriers of the T786C polymorphism was observed between patients with unruptured IA and those with aSAH, with an increased proportion of CC homozygotes in the aSAH group. The risk of rupture was higher in patients with the CC genotype. Multilobular aneurysms and those located in the posterior circulation had a higher incidence of rupture. Associations between arterial hypertension and certain genotypes were also found. However, no significant interaction was observed between the polymorphisms and established risk factors in relation to aneurysm rupture.

Conclusion: Our data showed a significant and independent correlation between eNOS genetic polymorphism T786C and aSAH.

Objective: Cannabidiol (CBD) is one of the most prominent non-psychotropic cannabinoids with known therapeutic potentials. Based on its anti-seizure efficacy, the first cannabis derived pharmaceutical grade CBD-based medication was approved in the USA in 2018 for the treatment of seizures in patients 2 years and older. Despite the effectiveness in reducing seizures, there remain several major questions on the optimization of CBD therapy for epilepsy such as the optimal dosage, composition, and route of delivery, which are the main objective of this current study.

Methods: We evaluated the antiseizure effects of CBD through different compositions, routes of delivery, and dosages in a pre-clinical model. We used a kainic acid-induced epilepsy model in C57BL/6 mice, treated them with placebo and/or CBD through inhalation, oral, and injection (intraperitoneal) routes. We used CBD broad spectrum (inhaled and intraperitoneal) vs CBD isolate formulations. We employed the Racine scaling system to evaluate the severity of the seizures, flow cytometry for measuring immune biomarkers and neurotrophic factors, and histologic analysis to examine and compare the groups.

Results: Our findings showed that all forms of CBD reduced seizures severity. Among the combination of CBD tested, CBD broad spectrum via inhalation was the most effective in the treatment of epileptic seizures (p < 0.05) compared to other forms of CBD treatments.

Conclusion: Our data suggest that route and CBD formulations affect its efficacy in the prevention of epileptic seizures. Inhaled broad spectrum CBD showed a potential superior effect compared to other delivery routes and CBD formulations in the prevention of epileptic seizures, which warrants further research.