Acta neurobiologiae experimentalis最新文献

This study evaluated the in vivo effects of hirudotherapy (medicinal leech therapy) on microcirculation and inflammation following global ischemia‑induced cerebral ischemia/reperfusion (I/R) in rats. Rats were divided into three groups of eight (control, I/R, and hirudotherapy) for this study. Global ischemia was created in the I/R and treatment groups by occluding both common carotid arteries. According to the I/R procedure, two Hirudo verbana leeches were applied bilaterally to the mastoid regions. Serum and tissue samples were analyzed for biochemical parameters including superoxide dismutase (SOD), interleukin 6 (IL‑6), nitric oxide (NO), calcitonin gene‑related peptide (CGRP), glutathione peroxidase (GPx), catalase (CAT), endothelin‑1, tumor necrosis factor alpha (TNF‑α), ischemia modified albumin (IMA), and hypoxia‑inducible factor‑1 alpha (HIF‑1α). Histopathological methods were used to examine edema, degeneration, necrosis, and hemorrhagic changes in brain tissue samples. The I/R group showed significantly increased tissue TNF‑α levels compared to controls. Tissue IMA and HIF‑1α levels were significantly higher in the treatment group. Treatment significantly reduced degeneration, necrosis, edema, and hemorrhage in brain tissues, as shown by histopathology. Histopathological analysis shows significantly less tissue damage in the hirudotherapy group compared to the I/R group, suggesting that hirudotherapy reduces brain damage after cerebral ischemia and reperfusion.

Ischemia-reperfusion injury remains a major cause of mortality and disability worldwide, with limited therapeutic options. While reperfusion is essential for tissue salvage, it paradoxically triggers secondary damage, highlighting the need to better understand regulated cell death pathways. Traditionally, apoptosis was considered the dominant mechanism; however, incomplete protection by caspase inhibition revealed a substantial contribution of caspase‑independent death. Among these, necroptosis has emerged as a functionally purposeful process, eliminating compromised cells but simultaneously amplifying sterile inflammation through the release of damage‑associated molecular patterns. This review synthesizes current knowledge of necroptosis in ischemia-reperfusion injury. We first establish its functional relevance, then examine canonical and non‑canonical molecular pathways, including RIPK1-RIPK3-MLKL signaling, mitochondrial dysfunction, and CaMKIIδ‑mediated execution. We discuss mechanisms of CASP8 checkpoint weakening and bypass, emphasizing the roles of metabolic collapse, oxidative stress, and ZBP1‑mediated signaling. Finally, we highlight the cell‑type and temporal dynamics of necroptosis, as well as its translational implications. Recognizing necroptosis as a context‑dependent permissive state rather than a simple backup pathway provides a more comprehensive framework for understanding ischemic cell death and its tissue‑specific manifestations.

During adolescence, the brain is particularly vulnerable to sleep disruption, which may lead to long‑term memory deficits and emotional dysregulation. This study investigated the impact of REM sleep deprivation (REM‑SD), applied specifically during the acquisition phase of learning, on spatial memory, anxiety‑like behavior, and hippocampal neurotrophic and oxidative status in adolescent rats. Male adolescent Wistar Albino rats were subjected to a REM‑SD protocol using the modified multiple platform method (MMPM), integrated directly into the training phase of the Morris water maze (MWM). Animals were divided into three groups: Control, Pedestal Control, and REM‑SD. Anxiety‑like behavior was assessed using the open field (OFT) and elevated plus maze (EPM) tests. Corticosterone levels and hippocampal levels of nerve growth factor (NGF), brain‑derived neurotrophic factor (BDNF), total oxidant status (TOS), total antioxidant status (TAS), superoxide dismutase (SOD), and malondialdehyde (MDA) were analyzed by ELISA. REM‑SD during the acquisition phase significantly impaired memory performance in the MWM probe trial. In the OFT test, REM‑SD rats exhibited increased anxiety‑like behavior, reflected by reduced time spent in the center zone, whereas the EPM demonstrated increased open‑arm duration. These behavioral alterations were accompanied by significantly elevated corticosterone levels. REM‑SD was associated with reduced hippocampal antioxidant status (decreased TAS and SOD), decreased NGF levels, and increased oxidative status (TOS). Our findings demonstrate that exposure to the MMPM, together with REM sleep disruption and associated stress‑related physiological responses, was accompanied by alterations in memory performance, corticosterone levels, oxidative balance, and neurotrophic markers. The observed behavioral changes, including alterations during late acquisition and impaired probe trial performance, may reflect combined effects on learning‑ and memory‑related processes.

It is well established that the circadian clock has pronounced effects on functioning of cells, tissues and body organs. Little, however, is known regarding its role in the body's adaptation to physical activity. The aim of the present study was to establish the effect of physical activity-performed at either the activity peak (ZT1) in the morning or during 'siesta' time (ZT6) in the middle of the day-on the lifespan of male and female Drosophila melanogaster. Three‑day‑old virgin flies (separated by sex) were allocated to control or exercise groups. Flies in the exercise groups were subjected to exercise every day by applying motor stimulation at ZT1 or at ZT6. Overall lifetime physical activity of controls was lower in male D. melanogaster compared to females. Forced physical activity at ZT1 prolonged the male lifespan by ~35%, whereas females in the same group exhibited a lifespan reduction of ~84%. In contrast, physical activity performed at 'siesta' time shortened the lifespan of both male and female flies, by ~20% and ~67%, respectively. Forced locomotor activity performed during the time of peak natural daily activity prolonged life expectancy in males but had a negative effect on female longevity. Interestingly, when physical activity was applied during the 'siesta' time, it shortened the lifespan regardless of sex. Therefore, our study suggests that synchronizing physical activity to the daily rhythm of activity and rest dictated by the circadian clock could be a new strategy for optimizing the effects of physical training. However, this interpretation requires further research involving human subjects of different chronotypes.

The basal forebrain septum separates the lateral ventricles and comprises the septum pellucidum and septum verum, the latter containing the septal nuclei. These nuclei are involved in cognitive, emotional, and autonomic function and are implicated in psychiatric and neurological disorders, including Alzheimer's disease. However, their detailed organization and connectivity remain insufficiently characterized in translational large‑animal models. In the present study, we investigated the anatomy and connectivity of the septal nuclei in the Göttingen minipig. Brain tissue was processed using Nissl staining and choline acetyltransferase immunohistochemistry, and neuronal connectivity was examined using magnetic resonance imaging‑guided stereotaxic tracer injections. The septum comprises medial, lateral, posterior, and ventral complexes with distinct cytoarchitectonic features. Cholinergic neurons were primarily located within the medial septal complex. Both medial and lateral septal nuclei received widespread afferent projections from cortical, limbic, diencephalic, and brainstem regions, including the hippocampus, amygdala, hypothalamus, thalamus, ventral tegmental area, and periaqueductal grey. The medial septal nuclei showed relatively stronger inputs from prefrontal cortical regions, whereas the lateral septal nuclei received more prominent projections from brainstem structures. Reciprocal intrinsic connections within the septal region were also observed. These findings extend current knowledge of septal organization in the Göttingen minipig and support its use as a model for studying septal circuitry and related disorders.

Proliferating cell nuclear antigen (PCNA) forms subnuclear replication patterns that report S‑phase progression with a single marker and provide an imaging readout of the replication factor C (RFC)‑PCNA axis. We benchmarked lightweight convolutional neural networks for classifying fixed HeLa cell PCNA images as G1, early S, mid S, or late S, and then applied the best‑performing model to live‑cell RFC control and RFC‑del datasets. MobileNetV2 provided the best balance of accuracy and inference cost in the fixed‑cell benchmark. In live‑cell traces, RFC‑del cells showed prolonged late S‑like PCNA pattern duration, whereas mid S‑like duration and peak‑distance metrics did not show clear group separation. These findings support lightweight PCNA‑pattern classification as a practical tool for quantitative replication‑pattern phenotyping and indicate a possible future application to neurobiological imaging, such as automated quantification of pro liferating cells in neurogenesis studies.

Glioblastomas, the most common primary malignant brain tumors, are characterized by their aggressive nature and poor prognosis. One significant aspect of glioblastoma biology is the transformation of astrocytes into a reactive state that supports tumor progression. This transformation is mediated by various signaling factors secreted by tumor cells, including extracellular vesicles carrying non‑coding RNAs and other bioactive molecules. This review explores the regulatory mechanisms and pathways linking glioblastoma and astrocytes and summarizes currently available in vitro models to study these interactions. Understanding the relationships between tumor cells and astrocytes is crucial for identifying novel therapeutic targets to combat this aggressive tumor.

Proton pump inhibitors are widely used, but their long‑term effects on the central nervous system are not well understood. In this study, we investigated whether chronic pantoprazole use alters sensorimotor function, oxidative stress, inflammatory response, and apoptosis in the motor cortex and cerebellum. Twenty‑one female Wistar rats were randomized to control (C), gavage control (GC), or pantoprazole (P; 20 mg/kg/day for 12 weeks) groups. Sensorimotor coordination (rotarod), water‑maze swim velocity, and open‑field locomotion were assessed as behavioral parameters. The cortical and cerebellar tissues were analyzed by Enzyme‑Linked Immunosorbent Assay (ELISA) for apoptosis, inflammation, and oxidative stress. Pantoprazole impaired sensorimotor coordination compared to both control groups. However, its effects on swim velocity and locomotor activity were primarily significant when compared to the naive control group, suggesting that gavage‑related stress may have contributed to these behavioral outcomes. Bcl‑2‑associated X protein (BAX) and Bcl‑2 associated agonist of cell death (BAD) protein levels and the BAX/Bcl‑2 ratio increased with pantoprazole, particularly in the motor cortex, indicating enhanced pro‑apoptotic activity. While tumor necrosis factor levels did not change, interleukin (IL)‑6 and IL‑1β levels were significantly higher in the cerebellum, suggesting neuroinflammatory activation associated with both pantoprazole and gavage‑induced stress. Furthermore, oxidative stress analyses revealed elevated malondialdehyde and oxidative stress index levels, as well as increased total antioxidant status, in specific regions, suggesting an imbalance between oxidative and antioxidant responses. Chronic pantoprazole administration resulted in modest motor deficits and region‑specific molecular alterations, including a pro‑apoptotic shift in the motor cortex. In addition, an inflammatory/compensatory antioxidant response in the cerebellum was observed due to both gavage‑induced stress and pantoprazole administration. These findings highlight the need for further studies on dose‑response, reversibility, and synaptic consequences, and suggest the importance of considering the risks of prolonged proton pump inhibitors exposure.

In vivo electrophysiological experiments were conducted to evaluate the effects of intraventricular and cortical administration of orexins on electrically evoked epileptiform discharges (EEDs) in the hippocampal CA1 field. Bipolar electrodes were stereotaxically implanted into the CA1 region of anesthetized rats, and epileptiform activity was induced by high‑frequency electrical stimulation (HFES). Orexin‑A and orexin‑B (10 μg/10 μl) were administered into the lateral ventricle or applied to the frontal cortex. Intracerebroventricular administration of orexin‑A significantly reduced the duration of EEDs within 20 minutes and abolished the progressive, HFES‑related prolongation of epileptiform discharges observed in control animals. In contrast, cortical administration of orexin‑A selectively reduced the incidence of high‑amplitude (7-10 mV) population spikes during EEDs without affecting the duration of epileptiform activity. Neither cortical nor intraventricular administration of orexin‑B produced significant changes in evoked epileptiform activity in the CA1 field, suggesting a possible involvement of OX1 receptor signaling in mediating the effects of orexin‑A. The differential effects observed after cortical versus intraventricular administration of orexin‑A appear to reflect site‑specific mechanisms of action. The effects of intraventricular administration of orexin‑A were predominantly induced via direct activation of hippocampal orexinergic receptors, whereas cortical application of orexin‑A induced its effects via modulation of cortico‑hippocampal mechanisms.

Scopolamine, a muscarinic acetylcholine receptor antagonist, disturbs learning and memory processes. Clozapine, an atypical antipsychotic, has beneficial predictive validity for confirming principles to help new treatment approaches. It could improve the cognitive deficit. Furthermore, clozapine has affinity for the cholinergic and GABAergic receptors. This investigation examined the effects of clozapine and/or GABAA receptor drugs on scopolamine‑induced memory impairment in male mice. Step‑down passive avoidance and open‑field tests were utilized for assessing memory acquisition and locomotor activity, respectively. The results exhibited that pre‑training administration of muscimol but not bicuculline induced amnesia without affecting locomotor activity. Moreover, pre‑training administration of clozapine did not significantly modify memory acquisition, but co‑administration of scopolamine and clozapine improved the amnesia produced with scopolamine. Also, co‑administration of muscimol along with clozapine potentiated memory impairment induced by scopolamine, whereas co‑injection of bicuculline along with clozapine reversed memory impairment produced by scopolamine. These treatments did not significantly change locomotor activity. Based on the findings, it is concluded that the GABAergic system modulates memory acquisition, and clozapine interacts with both muscarinic and GABAergic systems to bidirectionally regulate scopolamine‑induced amnesia. These results suggest the potential involvement of GABAergic mechanisms in the memory‑impairing effects of scopolamine and highlight the therapeutic potential of clozapine in mitigating cholinergic dysfunction‑related memory deficits.