Search Results (2,819)

Experimental animal studies of hypoxic–ischemic injury of the hippocampus of pigs are limited due to the unprecise definition of hippocampal subfields, cornu ammonis 1 to 4, compared to humans. Given that the pig model closely mirrors human physiology and serves as an important model for critical care research, a more precise description is necessary to draw valid conclusions applicable to human diseases. In our study, we were able to precisely define the CA2 and its adjacent regions in a domestic pig model by arginine vasopressin receptor 1B (AVPR1B) and calbindin-D28K like (CaBP-Li) expression patterns. Our findings demonstrate that the histoarchitecture of the porcine cornu ammonis subfields closely resembles that of the human hippocampus. Notably, we identified unusually strong neuronal damage in regions of the pig hippocampus following global ischemia, which are typically not susceptible to hypoxic–ischemic damage in humans. Full article

The intracerebral spread of tau is a critical mechanism associated with functional decline in Alzheimer’s disease (AD) and other tauopathies. Recently, a hypothesis has emerged suggesting that tau propagation is linked to functional neuronal connections, specifically driven by neuronal hyperactivity. However, experimental validation of this hypothesis remains limited. In this study, we investigated how tau propagation from the entorhinal cortex to the hippocampus, the neuronal circuit most susceptible to tau pathology in AD, is affected by the selective stimulation of neuronal activity along this circuit. Using a mouse model of seed-induced propagation combined with optogenetics, we found that the chronic stimulation of this neuronal connection over a 4-week period resulted in a significant increase in insoluble tau accumulation in both the entorhinal cortex and hippocampus. Importantly, the ratio of tau accumulation in the hippocampus relative to that in the entorhinal cortex, serving as an indicator of transcellular spreading, was significantly higher in mice subjected to chronic stimulation. These results support the notion that abnormal neuronal activity promotes tau propagation, thereby implicating it in the progression of tauopathy. Full article

Oleoylethanolamide (OEA) is a lipid with anti-inflammatory activity that modulates multiple reward-related behaviors. Previous studies have shown that OEA treatment reduces alcohol self-administration (SA) while inhibiting alcohol-induced inflammatory signaling. Nevertheless, the specific mechanisms that OEA targets to achieve these effects have not been widely explored. Here, we tested the effects of OEA treatment during alcohol SA, extinction or previous to cue-induced reinstatement of alcohol seeking. In addition, we measured gene expression changes in the striatum and hippocampus of relevant receptors for alcohol consumption (Drd1, Drd2, Cnr1, Oprm) as well as immune-related proteins (Il-6, Il-1β, Tlr4) and the brain-derived neurotrophic factor (Bdnf). Our results confirmed that when administered contingently, systemic OEA administration reduced alcohol SA and attenuated cue-induced reinstatement. Interestingly, we also observed that OEA treatment reduced the number of sessions needed for the extinction of alcohol seeking. Biochemical analyses showed that OEA induced gene expression changes in dopamine and cannabinoid receptors in the striatum and hippocampus. In addition, OEA treatment modulated the long-term immune response and increased Bdnf expression. These results suggest that boosting OEA levels may be an effective strategy for reducing alcohol SA and preventing relapse. Full article

Repeated exposure to tobacco smoke causes neuroinflammation and neuroplasticity, which correlates with smoking withdrawal-induced anxiety. The purpose of this study was to investigate the anticipated involvement of antioxidant-rich nanoparticles (NPs) prepared by oxidation-triggered polymerization of green tea catechins in impacting these effects in a rat model of tobacco smoke exposure. Exposure to tobacco smoke was carried out for 2 h a day, 5 days a week, for a total of 36 days. Weekly behavioral tests were conducted prior to recommencing the exposure. Following a 20-day exposure period, rats were administered either distilled water or green tea (GT) NPs (20 mg/kg, orally) for an additional 16 days. Our findings revealed that tobacco smoke exposure induced anxiety-like behavior indicative of withdrawal, and this effect was alleviated by GT NPs. Tobacco smoke exposure caused a marked increase in the relative mRNA and protein expression of nuclear factor-kappa B (NF-κB) and reduced the relative mRNA and protein expression of brain-derived neurotrophic factor (BDNF) in the hippocampus (HIP) and hypothalamus (HYP) brain subregions. The intervention of GT NPs effectively inhibited these effects. Our findings demonstrate the potent protective role of GT NPs in reducing withdrawal-induced anxiety-like behavior, neuroinflammation, and neuroplasticity triggered by tobacco smoke exposure. Full article

Soybean alleviates cognitive impairment. In our preparatory experiment, we found that dry-heat (90 °C for 30 min)-processed soybean embryo ethanol extract (hSE) most potently suppressed lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α expression in BV2 cells among dry-heat-, steaming-, and oil exclusion-processed soybean embryo ethanol extracts (SEs). Heat processing increased the absorbable soyasaponin Bb content of SE. Therefore, we investigated whether hSE and its supplement could mitigate LPS-impaired cognitive function in mice. Among dry-heat-, steaming-, and oil exclusion-processed SEs, hSE mitigated LPS-impaired cognitive function more than parental SE. hSE potently upregulated LPS-suppressed brain-derived neurotropic factor (BDNF) expression in the hippocampus, while LPS-induced TNF-α and IL-1β expression in the hippocampus and colon were downregulated. Lactobacillus gasseri NK109 additively increased the cognitive function-enhancing activity of hSE in mice with LPS-induced cognitive impairment as follows: the hSE and NK109 mix potently increased cognitive function and hippocampal BDNF expression and BDNF-positive neuron cell numbers and decreased TNF-α expression and NF-κB-positive cell numbers in the hippocampus and colon. These findings suggest that hSE and its supplement may decrease colitis and neuroinflammation by suppressing NF-κB activation and inducing BDNF expression, resulting in the attenuation of cognitive impairment. Full article

Epilepsy is one of the most frequently diagnosed neurological diseases, but the neurobiological basis of the disease remains poorly understood. Immunophenotyping CBA mice brain (NeuN and caspase-8) in parallel with hippocampal neurons’ functional status and survival rate assessment during acute epileptic PTZ-induced seizures is of particular interest. The aims of this study were to investigate the involvement of NeuN and caspase-8 in cell cycle regulation and the death of hippocampal neurons during PTZ-induced seizures in mice and to assess the therapeutic efficacy of Myricetin in the aforementioned experimental settings. Male CBA mice (n = 340) were divided into six groups to investigate the neuroprotective and antiepileptic effects of Myricetin and Valproic Acid in the PTZ-induced seizure model. Group I (control, n = 20) received a single intraperitoneal injection of NaCl 0.9% solution. Group II (PTZ only, n = 110) received a single intraperitoneal 45 mg/kg PTZ to induce seizures. Group III (Myricetin + PTZ, n = 90) was administered Myricetin orally at 200 mg/kg for 5 days, followed by a PTZ injection. Group IV (Valproic Acid + PTZ, n = 80) received intraperitoneal Valproic Acid at 100 mg/kg for 5 days, followed by PTZ. Group V (Myricetin + NaCl, n = 20) received Myricetin and NaCl. Group VI (Valproic Acid + NaCl, n = 20) received Valproic Acid and NaCl. Seizure severity was monitored using the modified Racine scale. Behavioral assessments included sensorimotor function tests, motor coordination using the rotarod test, and cognitive function via the Morris water maze. Brain tissues were collected and analyzed for oxidative stress markers, including malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH). Blood samples were analyzed for cytokine levels (IL-1β, IL-6, and TNF-α). Histological studies involved H&E and Nissl staining to evaluate general histopathology and neuronal density. Immunohistochemical analysis was conducted using antibodies against NeuN and caspase-8 to assess neuronal cell cycle regulation and apoptosis. PTZ-induced seizures caused significant oxidative stress and inflammation, leading to neuronal damage. Biochemical analyses showed elevated levels of MDA, SOD, GSH, IL-1β, IL-6, and TNF-α. Histological and immunohistochemical evaluations revealed a significant increase in caspase-8-positive neurons and a decrease in NeuN-positive neurons in the hippocampus and other brain regions, correlating with seizure severity. Myricetin and Valproic Acid treatments reduced oxidative stress markers and neuronal damage. Both treatments resulted in moderate neuronal protection, with fewer damaged neurons observed in the hippocampus, dentate gyrus, and other brain areas compared to the PTZ-only group. Summarizing, Myricetin administration showed promising neuroprotective effects. It significantly reduced oxidative stress markers, including MDA, and restored antioxidant enzyme activities (SOD and GSH), suggesting its antioxidative potential. Myricetin also effectively attenuated the elevation of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α, indicating strong anti-inflammatory properties. Behavioral assessments revealed that Myricetin improved cognitive and motor functions in PTZ-treated mice, with notable reductions in seizure severity and mortality rates. Histological analyses supported these behavioral findings, with Nissl staining showing reduced neuronal damage and NeuN staining indicating better preservation of neuronal integrity in Myricetin-treated groups. Additionally, caspase-8 staining suggested a significant reduction in neuronal apoptosis. Full article

The brain receives information via sensory inputs through the peripheral nervous system and stores a small subset as memories within the central nervous system. Short-term, working memory is present in the hippocampus whereas long-term memories are distributed within neural networks throughout the brain. Elegant studies on the mechanisms for memory storage and the neuroeconomic formulation of human decision making have been recognized with Nobel Prizes in Physiology or Medicine and in Economics, respectively. There is a wide gap, however, in our understanding of how memories of disparate bits of information translate into “knowledge”, and the neural mechanisms by which knowledge is used to make decisions. I propose that the conceptualization of a “knowledge network” for the creation, storage and recall of knowledge is critical to start bridging this gap. Knowledge creation involves value-driven contextualization of memories through cross-validation via certainty-seeking behaviors, including rumination or reflection. Knowledge recall, like memory, may occur via oscillatory activity that dynamically links multiple networks. These networks may show correlated activity and interactivity despite their presence within widely separated regions of the nervous system, including the brainstem, spinal cord and gut. The hippocampal–amygdala complex together with the entorhinal and prefrontal cortices are likely components of multiple knowledge networks since they participate in the contextual recall of memories and action selection. Sleep and reflection processes and attentional mechanisms mediated by the habenula are expected to play a key role in knowledge creation and consolidation. Unlike a straightforward test of memory, determining the loci and mechanisms for the storage and recall of knowledge requires the implementation of a naturalistic decision-making paradigm. By formalizing a neuroscientific concept of knowledge networks, we can experimentally test their functionality by recording large-scale neural activity during decision making in awake, naturally behaving animals. These types of studies are difficult but important also for advancing knowledge-driven as opposed to big data-driven models of artificial intelligence. A knowledge network-driven understanding of brain function may have practical implications in other spheres, such as education and the treatment of mental disorders. Full article

Postpartum depression (PPD) affects 174 million women worldwide and is characterized by profound sadness, anxiety, irritability, and debilitating fatigue, which disrupt maternal caregiving and the mother–infant relationship. Limited pharmacological interventions are currently available. Our understanding of the neurobiological pathophysiology of PPD remains incomplete, potentially hindering the development of novel treatment strategies. Recent hypotheses suggest that PPD is driven by a complex interplay of hormonal changes, neurotransmitter imbalances, inflammation, genetic factors, psychosocial stressors, and hypothalamic–pituitary–adrenal (HPA) axis dysregulation. This narrative review examines recent clinical studies on PPD within the past 15 years, emphasizing advancements in neuroimaging findings and blood biomarker detection. Additionally, we summarize recent laboratory work using animal models to mimic PPD, focusing on hormone withdrawal, HPA axis dysfunction, and perinatal stress theories. We also revisit neurobiological results from several brain regions associated with negative emotions, such as the amygdala, prefrontal cortex, hippocampus, and striatum. These insights aim to improve our understanding of PPD’s neurobiological mechanisms, guiding future research for better early detection, prevention, and personalized treatment strategies for women affected by PPD and their families. Full article

Vascular cognitive impairment and dementia (VCID) is the second leading cause of dementia. There is currently no effective treatment for VCID. Resveratrol (RSV) is considered an antioxidant; however, our group has observed pleiotropic effects in stroke paradigms, suggesting more effects may contribute to mechanistic changes beyond antioxidative properties. The main goal of this study was to investigate if administering RSV twice a week could alleviate cognitive declines following the induction of a VCID model. Additionally, our aim was to further describe whether this treatment regimen could decrease cell death in brain areas vulnerable to changes in cerebral blood flow, such as the hippocampus and medial septum. We hypothesized RSV treatments in a mouse model of gradual cerebral hypoperfusion protect against cognitive impairment. We utilized gradual bilateral common carotid artery stenosis (GBCCAS) via the surgical implantation of ameroid constrictor devices. RSV treatment was administered on the day of implantation and twice a week thereafter. Cerebral perfusion was measured by laser speckle contrast imaging, and cognitive functions, including the recognition memory, the spatial working memory, and associative learning, were assessed by novel object recognition (NOR), Y-maze testing, and contextual fear conditioning (CFC), respectively. RSV treatment did not alleviate cerebral perfusion deficits but mitigated cognitive deficits in CFC and NOR after GBCCAS. Despite these deficits, no hippocampal pathology was observed; however, cholinergic cell loss in the medial septum was significantly increased after GBCCAS. This cholinergic cell loss was mitigated by RSV. This study describes a novel mechanism by which chronic RSV treatments protect against a VCID-induced cognitive decline through the preservation of cholinergic cell viability to improve memory performance. Full article

Achieving sustainable resource use is a priority to meet future challenges. The Gulf of Cádiz, located in the Atlantic waters of southern Europe, is home to a significant fishing fleet due to the richness and diversity of its ecosystems. Managing this area is complex due to the diversity of variables, including social, ecological, and oceanographic factors. Therefore, multidisciplinary approaches are proposed for implementing conservation strategies. One strategy for defining area-based management measures is through the use of flagship species, such as seahorses. These emblematic animals can assist in defining such measures. However, there is currently scarce information on the occurrence of seahorses in the Gulf of Cádiz. In this study, we present the first occurrence data of two species of the genus Hippocampus (H. hippocampus and H. guttulatus) in this area. The Gulf of Cádiz is not only described as the southernmost region of their distribution in continental Europe, but it is also a significant landmark for the genus Hippocampus, as one adult was captured at a depth of up to 101 m. Five management areas based on differentiated benthic habitats are proposed. We believe that our study has the potential to significantly improve conservation of seahorses and induce a positive impact on the ecosystem. Full article

The distinct clinical and radiological characteristics of right temporal variant FTD have only been recently recognized. Methods: Eight patients with right temporal variant FTD were prospectively recruited and underwent a standardised neuropsychological assessment, clinical MRI, and quantitative neuroimaging. Results: Our voxelwise grey analyses captured bilateral anterior and mesial temporal grey matter atrophy with a clear right-sided predominance. Bilateral hippocampal involvement was also observed, as well as disease burden in the right insular and opercula regions. White matter integrity alterations were also bilateral in anterior temporal and sub-insular regions with a clear right-hemispheric predominance. Extra-temporal white matter alterations have also been observed in orbitofrontal and parietal regions. Significant bilateral but right-predominant thalamus, putamen, hippocampus, and amygdala atrophy was identified based on subcortical segmentation. The clinical profile of our patients was dominated by progressive indifference, decline in motivation, loss of interest in previously cherished activities, incremental social withdrawal, difficulty recognising people, progressive language deficits, increasingly rigid routines, and repetitive behaviours. Conclusions: Right temporal variant FTD has an insidious onset and may be mistaken for depression at symptom onset. It manifests in a combination of apathy, language, and behavioural features. Quantitative MR imaging captures a characteristic bilateral but right-predominant temporal imaging signature with extra-temporal frontal and parietal involvement. Full article

Background: Depression is one of the most severe sequelae of COVID-19, with major depressive disorder often characterized by disruption in white matter (WM) connectivity stemming from changes in brain myelination. This study aimed to quantitatively assess brain myelination in clinically diagnosed post-COVID depression (PCD) using the recently proposed MRI method, macromolecular proton fraction (MPF) mapping. Methods: The study involved 63 recovered COVID-19 patients (52 mild, 11 moderate, and 2 severe) at 13.5 ± 10.0 months post-recovery, with matched controls without prior COVID-19 history (n = 19). A post-COVID depression group (PCD, n = 25) was identified based on psychiatric diagnosis, while a comparison group (noPCD, n = 38) included participants with neurological COVID-19 complications, excluding clinical depression. Results: Fast MPF mapping revealed extensive demyelination in PCD patients, particularly in juxtacortical WM (predominantly occipital lobe and medial surface), WM tracts (inferior fronto-occipital fasciculus (IFOF), posterior thalamic radiation, external capsule, sagittal stratum, tapetum), and grey matter (GM) structures (hippocampus, putamen, globus pallidus, and amygdala). The noPCD group also displayed notable demyelination, but with less magnitude and propagation. Multiple regression analysis highlighted IFOF demyelination as the primary predictor of Hamilton scores, PCD presence, and severity. The number of post-COVID symptoms was a significant predictor of PCD presence, while the number of acute symptoms was a significant predictor of PCD severity. Conclusions: This study, for the first time, reveals extensive demyelination in numerous WM and GM structures in PCD, outlining IFOF demyelination as a key biomarker. Full article

As an important part of environmental science and water resources management, water quality prediction is of great importance. In order to improve the efficiency and accuracy of predicting dissolved oxygen (DO) at the outlet of a reservoir, this paper proposes an improved Seahorse Optimizer to enhance the hybrid kernel extreme learning machine model for water quality prediction. Firstly, the circle chaotic map is used to initialize the hippocampus population to improve the diversity and quality of the population, and then the sine and cosine strategy is used to replace the predation behavior of the hippocampus to improve the global search ability. Finally, the lens imaging reverse learning strategy is used to expand the search range and prevent it from falling into the local optimal solution. By introducing two kernel functions, a global kernel function (Poly) and a local kernel function (RBF), a new hybrid kernel function extreme learning machine is formed by linearly combining these two kernel functions. The parameters of this HKELM are optimized with the improved Seahorse Optimizer, and the water quality prediction model of CZTSHO-HKELM is constructed. The simulation results show that the operating efficiency and prediction accuracy of the model are better than those of the ELM, CZTSHO-ELM, CZTSHO-KELM, and SHO-HKELM models, with the correlation coefficients increased by 5.5%, 3.3%, 3.4%, and 7.4%, respectively. The dissolved oxygen prediction curve is close to the actual dissolved oxygen change, which can better meet the requirements of reservoir water quality prediction. The above method can be applied to further accurately predict the water quality of the reservoir. Full article

Compensatory changes in brain connectivity keep motor symptoms mild in prodromal Parkinson’s disease. Studying compensation in patients is hampered by the steady progression of the disease and a lack of individual baseline controls. Furthermore, combining fMRI with walking is intricate. We therefore used a seed-based metabolic connectivity analysis based on 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) uptake in a unilateral 6-OHDA rat model. At baseline and in the chronic phase 6–7 months after lesion, rats received an intraperitoneal injection of [¹⁸F]FDG and spent 50 min walking on a horizontal treadmill, followed by a brain PET-scan under anesthesia. High activity was found in the cerebellar anterior vermis in both conditions. At baseline, the anterior vermis showed hardly any stable connections to the rest of the brain. The (future) ipsilesional cerebellar hemisphere was not particularly active during walking but was extensively connected to many brain areas. After unilateral dopamine depletion, rats still walked normally without obvious impairments. The ipsilesional cerebellar hemisphere increased its activity, but narrowed its connections down to the vestibulocerebellum, probably aiding lateral stability. The anterior vermis established a network involving the motor cortex, hippocampus and thalamus. Adding those regions to the vermis network of (previously) automatic control of locomotion suggests that after unilateral dopamine depletion considerable conscious and cognitive effort has to be provided to achieve stable walking. Full article

This study investigated the neuroprotective effect of 70% ethanol extract of Ecklonia cava (EE) in amyloid beta (Aβ)-induced cognitive deficit mice. As a result of analyzing the bioactive compounds in EE, nine compounds were identified using ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). In particular, the diekcol content was quantified by high-performance liquid chromatography with diode-array detection (DAD-HPLC). Biochemical analysis was performed on brain tissue to determine the mechanism of the cognitive function improvement effect of EE. The result showed that EE ameliorated learning and memory decline in behavioral tests on Aβ-induced mice. EE also attenuated oxidative stress by regulating malondialdehyde (MDA) content, reduced glutathione (GSH), and superoxide dismutase (SOD) levels. Similarly, EE also improved mitochondrial dysfunction as mitochondrial membrane potential, ATP production, and reactive oxygen species (ROS) levels. In addition, EE enhanced synapse function by modulating acetylcholine-related enzymes and synaptic structural proteins in the whole brain, hippocampus, and cerebral cortex tissues. Also, EE regulated Aβ-induced apoptosis and inflammation through the c-Jun N-terminal kinase (JNK) and nuclear factor-kappa B (NF-κB) signaling pathways. Furthermore, EE protected neurotoxicity by increasing brain-derived neurotrophic factor (BDNF) production. These results suggest that EE may be used as a dietary supplement for the prevention and treatment of Alzheimer’s disease (AD). Full article