Search Results (3,371)

Parkinson’s disease (PD) involves motor and cognitive impairment that nicotinic acetylcholine receptors (nAChRs) such as the α7 subtype are responsible for regulating. The hippocampus, abundant in α7 nAChRs, was quantitatively evaluated for [¹²⁵I]α-bungarotoxin ([¹²⁵I]α-Bgtx) binding to α7 nAChRs in postmortem human PD (n = 26; 12 male, 14 female) and cognitively normal (CN) (n = 29; 14 male, 15 female) brain slices. Anti-ubiquitin and anti-α-synuclein immunostained adjacent slices were analyzed using QuPath. Autoradiographs of [¹²⁵I]α-Bgtx radioligand binding were analyzed in OptiQuant. Ubiquitin and α-synuclein distribution generally aligned with the distribution of α7 nAChRs detected by [¹²⁵I]α-Bgtx. Binding of [¹²⁵I]α-Bgtx in PD cases was significantly greater than CN with a 32% increase in gray matter binding. A weak positive correlation between age and [¹²⁵I]α-Bgtx binding was found in both PD and CN. In comparison to Alzheimer’s disease hippocampus, [¹²⁵I]α-Bgtx binding in PD gray matter was higher by 41%. Differences in nAChR expression imply unique roles depending on the neurodegenerative pathology. PD may experience an increase in α7 nAChRs as a compensatory mechanism to the loss in neurons, highlighting its neuroprotective capabilities. [¹²⁵I]α-Bgtx shows potential as a radioligand for α7 nAChRs to elucidate the complexities of PD pathology. Full article

The resin extract of Garcinia nigrolineata (GNR-E), a tropical plant used in Southeast Asian traditional medicine, was evaluated for its antidepressant-like effects in a chronic mild stress (CMS) mouse model, with imipramine as a reference drug. GNR-E dose-dependently alleviated CMS-induced anhedonia (sucrose preference test) and behavioral despair (forced swimming and tail suspension tests). Neurochemical analyses revealed that GNR-E increased serotonin (5-HT) and norepinephrine (NE) levels, reduced expression of their transporters (SERT, NET) and receptors (5-HT1A, 1B, 2A, 2C, 7; α2A, 2C) in the frontal cortex and hippocampus, and normalized HPA-axis hyperactivity by lowering serum corticosterone and modulating glucocorticoid receptor (GR) and SGK-1 mRNA expression. In vitro, GNR-E inhibited monoamine oxidase (MAO)-A and -B (Ki = 2.33 and 1.55 µg/mL, respectively). Phytochemical analysis identified xanthones, particularly cowanin, as key constituents. These findings highlight GNR-E’s potential as a novel plant-based antidepressant, warranting further investigation into its active compounds and clinical applications. Full article

Objective: Neuronal growth regulator 1 (Negr1) is a GPI-anchored neuronal cell adhesion molecule of the IgLON superfamily associated with multiple psychiatric disorders. This study aimed to investigate behavioral and molecular adaptations to social isolation (SI) stress in Negr1-deficient (Negr1^−/−) mice. Methods: Male and female Negr1^−/− and wild-type (Wt) mice (n = 10 per group) were exposed to two weeks of SI or group housing (Ctl). Behavioral assays assessed exploratory and anxiety-like behavior. Gene expression analyses in the prefrontal cortex and hippocampus were performed using RT-qPCR, focusing on GABAergic, neurotrophic, and IgLON family genes. Results: SI-induced weight loss in Negr1^−/− mice compared to Wt was evident in both sexes but more pronounced in males. Behaviorally, SI Wt males showed stress-induced hyperactivity compared to Ctl Wt, whereas SI Negr1^−/− males exhibited blunted exploratory behavior relative to SI Wt in the open field test (OFT). Negr1^−/− females showed reduced exploration in the elevated plus maze (EPM), suggesting increased anxiety. Hippocampal Pvalb was downregulated in SI Negr1^−/− mice of both sexes compared to Wts, with a stronger decrease in males, indicating heightened male vulnerability in GABAergic interneuron function. In males, SI reduced hippocampal Bdnf in both genotypes, whereas Ntrk2 (TrkB) upregulation occurred only in Negr1^−/− mice, suggesting a genotype-specific compensatory response. Hippocampal expression of Fgfr2 and IgLON members (Ntm1a/1b, Lsamp1a/1b) was increased in SI Negr1^−/− males compared to SI Wt, with minimal changes in females. Conclusions: Negr1 deficiency leads to sex-specific behavioral and molecular adaptations to social isolation stress, highlighting the role of Negr1 in modulating neurotrophic and GABAergic signaling pathways under adverse environmental conditions. Full article

The brain and the immune system communicate in many ways and interact directly at neuroimmune interfaces at brain borders, such as hippocampus, choroid plexus, and gateway reflexes. The first part of this review described intercellular communication (synapses, extracellular vesicles, and tunneling nanotubes) during homeostasis and neuroimmunomodulation upon dysfunction. This second part compares spatial orientation, learning, and memory function in both systems. The hippocampus, deep in the medial temporal lobes of the brain, is reported to play a central role in all three functions. Its medial entorhinal cortex contains neuronal spatial cells (place cells, head direction cells, boundary vector cells, and grid cells) that facilitate spatial navigation and allow the construction of cognitive maps. Sensory input (about 100 megabytes per second) via engram neurons and top down and bottom up information processing between the temporal lobes and other lobes of the brain are described to facilitate learning and memory function. Output impulses leave the brain via approximately 1.5 million fibers, which connect to effector organs such as muscles and glands. Spatial orientation in the immune system is described to involve gradients of chemokines, chemokine receptors, and cell adhesion molecules. These facilitate immune cell interactions with other cells and the extracellular matrix, recirculation via lymphatic organs (lymph nodes, thymus, spleen, and bone marrow), and via lymphatic fluid, blood, cerebrospinal fluid, and tissues. Learning in the immune system is summarized to include recognition of exogenous antigens from the outside world as well as endogenous blood-borne antigens, including tumor antigens. This learning process involves cognate interactions through immune synapses and the distinction between self and non-self antigens. Immune education via vaccination helps the process of development of protective immunity. Examples are presented concerning the therapeutic potential of memory T cells, in particular those derived from bone marrow. Like in the brain, memory function in the immune system is described to be facilitated by priming (imprinting), training, clonal cooperation, and an integrated perception of objects. The discussion part highlights evolutionary aspects. Full article

The extracellular matrix protein reelin is well known for orchestrating radial migration of cortical neurons during embryonic cortical development. While in the reeler mutant mouse, lacking reelin expression, radially migrating neurons are malpositioned and display dendritic malformations, no such deficits were found after conditionally induced reelin deficiency (Reln^cKO) in the hippocampus of mice aged two months. Here, we addressed the question whether or not Reln^cKO, when induced early after birth, might cause malformations of hippocampal neurons. For instance, we could recently show dendritic hypertrophy of somatosensory and entorhinal cortex neurons after early induced Reln^cKO. In the present study, reelin deficiency in Reln^cKO mice was induced immediately after birth, and the analysis of reconstructed Golgi-stained hippocampal neurons from these mice, when aged 4 weeks, revealed morphological malformations. Dentate granule cells were the most affected from all analyzed hippocampal neuronal cell types. Thus, Reln^cKO granule cells had a significantly smaller soma size and displayed atrophy of proximal dendritic segments when compared to wild type (wt). Malformations of interneurons were only subtle and cell type specific; thus, multipolar but not bitufted interneurons developed proximal dendritic hypertrophy. Also, the dendrite morphology of CA2- and CA3-pyramidal cells was affected, while we did not detect morphological changes of CA1-pyramidal cell dendrites. In summary, our results show that early postnatal Reln^cKO causes morphological malformations of hippocampal neurons, in particular of dentate granule cells. Taken together with our previous findings, we conclude that not only specific types of entorhinal- and neocortical neurons, but also types of hippocampal neurons are at risk of developing malformations if reelin expression is reduced during a critical early postnatal period. Full article

Background/Objectives: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for motor symptoms in Parkinson’s disease (PD), but concerns remain regarding its impact on cognitive function. Identifying neuroanatomical predictors of postoperative cognitive decline could improve patient selection and outcomes. This study aims to investigate the relationship between preoperative brain morphology and postoperative neuropsychological outcomes in PD patients undergoing bilateral STN-DBS. Methods: Thirty-eight PD patients underwent standardized neuropsychological testing and preoperative MRI before and 3–24 months after STN-DBS. Manual MRI morphometric measurements were obtained for 42 cortical, subcortical, and ventricular parameters. Changes in cognitive domains—including executive function, memory, language, visuospatial abilities, attention, and global cognition—were analyzed, and correlations between structural metrics and cognitive changes were assessed using Spearman’s coefficients. Results: Significant postoperative declines occurred selectively in language functions: verbal fluency (phonemic and semantic, d = −0.49 to −0.84) and confrontation naming (d = −0.47). Memory, executive functions, attention, and global cognition remained preserved. Enlarged lateral ventricles were consistently associated with poorer outcomes across multiple domains, while increased left precentral gyrus width correlated with executive and memory decline. Additionally, smaller midbrain and cingulate gyrus width were associated with greater executive impairment. Conclusions: STN-DBS in PD is associated with selective postoperative cognitive changes, most prominently in verbal fluency. Simple preoperative MRI morphometric measures, including ventricular size, limbic structure volumes, and specific cortical parameters, may serve as clinically feasible predictors of cognitive risk. Incorporating such measures into preoperative assessments could enhance patient selection, counseling, and individualized surgical planning. Full article

Mask optimization is a critical technique for enhancing imaging performance in digital micromirror device (DMD)-based maskless lithography. Conventional algorithms, however, often suffer from slow convergence and limited adaptability, particularly when handling complex multi-feature mask patterns. To address these challenges, this study proposes a hybrid Genetic–Hippo Optimization (GA-HO) algorithm that integrates the global exploration capability of the Genetic Algorithm (GA) with the local exploitation efficiency of the Hippocampus Optimization (HO) Algorithm. The approach employs grayscale modulation for adaptive mask optimization and introduces a global–local cyclic search mechanism to balance exploration and exploitation throughout the optimization process. Simulation results demonstrate that the GA-HO hybrid algorithm achieves a more pronounced improvement in overall optimization performance compared with the standard GA. In complex multi-line mask optimization, the standard GA achieves approximately a 18% enhancement in optimization accuracy, whereas the GA-HO algorithm achieves around a 30% improvement. Moreover, the GA-HO algorithm exhibits a smoother convergence curve, greater stability, and superior robustness. The hybrid method effectively suppresses linewidth variations and corner distortions caused by optical proximity effects (OPE), maintaining high imaging fidelity and stable optimization outcomes even under challenging mask conditions. Overall, the proposed GA-HO framework demonstrates excellent efficiency, adaptability, and precision, providing a reliable and high-performance solution for DMD-based maskless lithography. This work offers a strong theoretical and algorithmic foundation for advancing high-resolution, high-efficiency, and low-cost micro/nanofabrication technologies, highlighting the potential of heuristic hybrid optimization strategies for practical lithography applications. Full article

Cognitive impairment is acknowledged as an early stage between normal aging and Alzheimer’s disease, emphasizing the need for prompt intervention. There is growing evidence that the gut–brain axis plays a role in regulating cognitive function, indicating that probiotics and their derivatives may impact cognitive functions through the brain–gut axis. In this study, we isolated and identified a novel bacterial strain Limosilactobacillus fermentum IOB802 (IOB802) from traditionally fermented pickles. This strain showed promising probiotic properties, and its postbiotic was also prepared. Both the probiotic IOB802 and its postbiotic preparation significantly improved memory and learning abilities by using a mouse model with cognitive impairment induced by scopolamine. In comparison to the scopolamine group, IOB802 and IOB802 postbiotic administration decreased acetylcholinesterase activity by 59.2% and 29.51%, increased antioxidant enzyme activity by 44.45% and 29.43%, and lowered lipid peroxidation by 44.19% and 32.53%, respectively. Moreover, IOB802 postbiotic notably boosted acetylcholine levels by 72.08%. In addition, the treatments preserved the integrity of neurons in specific regions of the hippocampus, as shown by histological analysis. The IOB802 postbiotic increased the expression of neurotrophic factors BDNF and NGF by 1.36- and 1.73-fold, while reducing the expression of inflammatory cytokines TNF-α, IL-6, and IL-1β by 2.05-, 1.85-, and 2.46-fold, respectively. Compared to the scopolamine group, IL-6 and IL-1β expression decreased by 1.32- and 2.37-fold in the IOB802 group. Additionally, IOB802, especially its postbiotic, was found to restore disrupted intestinal flora caused by scopolamine. These findings suggest that IOB802 and its postbiotic can improve cognitive function through enhancing cholinergic activity, reducing oxidative stress, providing neuroprotection, and restoring gut microbiota composition. Postbiotics, in particular, may represent a promising alternative to live probiotics for supporting cognitive health. Full article

Background: This study was designed as a dosimetric feasibility analysis to compare hippocampal-avoidance whole-brain radiotherapy (HA-WBRT) using 3D-CRT, IMRT, and VMAT techniques, with particular attention to clinical applicability in resource-limited settings. While 3D-CRT was used as a reference for conventional WBRT, the primary aim was to determine whether IMRT can serve as an effective and accessible alternative to VMAT for HA-WBRT in centers without advanced technology infrastructure. Methods: Fifteen patients undergoing WBRT for symptom relief were planned using 3D-CRT, IMRT, and VMAT on the Elekta Monaco 6.1.4.0 system. Key organs at risk (OARs) such as the optic nerves, chiasm, eyes, and lenses were considered in the treatment planning. Plans were evaluated based on PTV dose distribution, Conformity Index (CI), Homogeneity Index (HI), and OAR dose constraints (RTOG 0933, NRG-CC001). Gamma pass rate analysis (3%/3 mm) was performed for the IMRT and VMAT plans. Results: IMRT and VMAT significantly reduced the hippocampal dose compared to 3D-CRT, with similar PTV coverage and OAR sparing. The mean D_max for the hippocampus was 15.4 Gy for IMRT and 15.5 Gy for VMAT compared to 31.2 Gy for 3D-CRT. The D100% for the hippocampus was 7.5 Gy for IMRT and 7.6 Gy for VMAT, both well below the RTOG 0933 threshold of 9 Gy, while 3D-CRT delivered 30.3 Gy. Additionally, IMRT and VMAT delivered lower doses to the optic nerves and chiasm. QA results showed gamma pass rates above 96% for all plans. This study focused solely on treatment-planning and dosimetric feasibility without evaluating patient outcomes or clinical follow-up. Conclusions: HA-WBRT with IMRT and VMAT significantly reduced the hippocampal dose while maintaining optimal PTV coverage. VMAT is preferred for its balance of efficacy, protection, and treatment time, while IMRT represents a feasible approach for facilities without VMAT, though it requires stricter dose control and longer treatment times. Full article

Background: The potential long-term effects of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection on the brain structure have not yet been fully elucidated. Even though existing studies have reported structural changes in the post-COVID-19 period, the results remain highly inconsistent and controversial. As such, identifying an imaging biomarker for post-COVID brains is still under investigation. This review aims to comprehensively summarize the structural MRI (sMRI) studies that focus on volumetric brain changes at least two weeks following COVID-19 infection. Methods: A systematic literature search was conducted on PubMed, SCOPUS, Web of Science, EMBASE, and Google Scholar up to 9 September 2025. Studies that utilized sMRI to assess volumetric brain changes post-COVID at greater than two weeks following infection were included. Exclusion criteria encompassed research involving pediatric or adolescent populations and imaging modalities other than sMRI. Preprints, reviews, case reports, case series and post-mortem studies were also excluded. Results: Forty-one studies satisfied the inclusion criteria and consisted of 2895 patients and 1729 healthy controls. Despite the wide variability in image acquisition protocols, data processing methods, and comorbidities between studies, multiple studies reported statistically significant volumetric reductions in the hippocampus, amygdala, thalamus, basal ganglia, nucleus accumbens and the cerebellum months to years after infection, especially in older hospitalized patients with severe COVID-19. Conclusions: The emerging literature reports long-term volume changes across various brain regions in individuals previously infected with COVID-19; however, the evidence is inconsistent. Specific imaging biomarkers following exposure to SARS-CoV-2 infection and the underlying mechanisms of these changes are yet to be identified. Future studies with harmonized imaging protocols, longitudinal designs, and integrated biomarker and clinical data are needed to define robust biomarkers and elucidate the pathophysiology of these findings. Full article

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social communication deficits, repetitive behaviors, and restricted interests. Although its pathogenesis is not fully understood, emerging evidence suggests a connection between gut microbiota alterations and ASD. The role of specific bacterial species, particularly Enterococcus faecium, in the development of ASD remains unclear. This study aimed to investigate the impact of E. faecium derived from the feces of autistic children on mice. Thirty male BALB/c mice were divided into three groups: control, E. coli, and E. faecium treatment groups. E. faecium was administered orally for 30 days. Behavioral assessments, including open field tests, sucrose preference, Y-maze, and social interaction tests, were performed to evaluate anxiety, depression, memory, and social behavior. Additionally, serum 5-HT levels were measured, and colon and brain tissues were analyzed for inflammation, blood–brain barrier (BBB) integrity, and histological changes. Stool DNA sequencing was used to assess microbiota diversity and composition. Treatment with E. faecium significantly altered behavior in mice, including increased anxiety, depression, impaired memory, and social dysfunction. Colon histology revealed severe damage, including increased inflammation, reduced tight junction protein expression, and decreased mucin-2 levels. Elevated serum lipopolysaccharide (LPS) levels indicated systemic inflammation, and gut microbiota analysis showed significant dysbiosis. In the brain, particularly within the hippocampus and cortical regions, E. faecium induced neural damage, heightened inflammation, and compromised blood–brain barrier integrity. Enterococcus faecium from autistic patients can induce significant behavioral changes in mice, potentially via gut microbiota dysbiosis, intestinal barrier disruption, and brain inflammation. These findings suggest that E. faecium may contribute to gut–brain axis dysregulation in ASD, although further mechanistic studies are warranted. Full article

Background: Post-traumatic stress disorder (PTSD) is a mental disorder that can develop after experiencing or witnessing a traumatic event. Dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis and alterations in neurotransmitters (gamma-aminobutyric acid (GABA) and glutamate) are the main pathologies of PTSD. In particular, altered GABAergic neurotransmission and reduced GABA activity are linked to PTSD. Given the low efficacy and side effects of serotonin reuptake inhibitors—the most common treatment for PTSD—a safer and more effective treatment is urgently needed. Bojungikgi-tang (BJIGT) is well-known herbal prescription in East Asia, which used to boost immunity and to alleviated symptoms such as chronic fatigue, poor appetite, and indigestion. However, its role in PTSD remains largely unexamined. This study aimed to investigate the effects of BJIGT in single-prolonged stress with shock (SPSS)-induced PTSD male mice for 2 weeks. Methods: To assess PTSD-like behaviors, we conducted open field, forced swimming, Y-maze, and contextual fear conditioning tests. To investigate the underlying mechanisms, we performed ELISA, Western blot, and immunohistochemistry. Results: BJIGT significantly ameliorated PTSD-like behaviors, including emotional and cognitive decline. Additionally, it restored serum corticosterone levels, regulated neuronal functions (c-Fos, DCX, and Prox1), and GABAergic neurotransmission-related factors (vGAT, GAD67, and parvalbumin) in the hippocampus of PTSD mice. Notably, in SPSS-induced PTSD mice, BJIGT effectively ameliorated pathological changes by modulating JNK-CaMKII and Pin1–β-catenin intracellular signaling. Conclusions: These findings revealed that BJIGT effectively improved PTSD-like emotional and cognitive decline by regulating the HPA axis and GABAergic neurotransmission in SPSS-induced PTSD mice, thereby promising to be an effective strategy for the treatment of PTSD. Full article

Alzheimer’s disease (AD) affects over 55 million individuals worldwide, yet no transformative disease-modifying therapies exist. Mathematical modelling provides a powerful framework to elucidate complex disease mechanisms, predict therapeutic outcomes, and enable precision medicine—capabilities urgently needed where multiscale spatiotemporal processes defy experimental analysis alone. We developed a mechanistic spatiotemporal model coupling four AD hallmarks: β-amyloid (Aβ) accumulation, T-protein (T-p) aggregation, neuroinflammation and electrical conductivity decline. Formulated as non-linear partial differential equations (p.d.es) on a 3-dimensional biological interpretation of non-linear terms (the ellipsoidal brain domain with biologically grounded parameters), the model was solved using eigenfunction expansion, Fourier analysis and numerical methods. Therapeutic interventions were simulated through mechanistically motivated parameter modifications and validated against longitudinal biomarker data from major cohort studies. Simulations reveal Aβ-initiated spatiotemporal cascades originating in the hippocampus and spreading radially at 0.15–0.20 cm/year, with T-pathology emerging after 2–3 years. Conductivity decline accelerates upon T-onset (year 5–7), reflecting the transition to symptomatic disease. Multimodal intervention at early symptomatic stages reduces peak Aβ by 36% and inflammation by 52% and preserves 41% more conductivity than untreated controls. Sensitivity analysis identifies Aβ production and inflammatory regulation as critical therapeutic targets, with dose–response curves demonstrating linear efficacy relationships. This biologically grounded framework explicitly links molecular pathology to functional decline, enabling patient-specific trajectory prediction through parameter calibration. The model establishes a foundation for precision medicine applications including individualized prognosis, optimal treatment timing and virtual clinical trial design, advancing quantitative systems biology of neurodegeneration. Full article

Background/Objectives: We previously reported that the flavanol (+)-epicatechin (+Epi) enhances adult mice short-term working memory and neurogenesis. This study aimed to characterize the effects of +Epi on short- and long-term memory, to modulate mitochondria structure/function, oxidative stress (OS) and inflammation associated cytokines in the hippocampus and pre-frontal cortex of aged rats. Methods: Experiments were conducted using aged (23 month old) male Sprague Dawley rats. The control group (n = 6/group) were exposed to vehicle (water) only while the treated group, was provided +Epi at 1 mg/kg/day by oral gavage for 8 weeks. Open-field recognition tests were used to evaluate short- and long-term memory. The hippocampus and frontal cortex were sampled and citrate synthase activity, ATP levels, mitochondrial proteins, cytokines (IL-1β, IL-6, TNF-a and IL-11), protein carbonylation, lipid peroxidation (malonaldehyde; MDA), superoxide dismutase 2 (SOD2), glutathione peroxidase (GPx) and catalase activity were quantified. Results: There was a significant improvement in both short- and long-term memory in the +Epi treated group vs. controls. Mitochondrial bioenergetics also improved with treatment as determined by increased citrate synthase activity and ATP content. Relative levels of the mitochondrial proteins mitofilin and complex V increased with +Epi. +Epi suppressed protein carbonyls and MDA levels. OS buffering systems were significantly enhanced with +Epi as per increases in SOD2, GPx and catalase enzyme activities. +Epi also decreased pro-inflammatory and stimulated anti-inflammatory cytokines vs. controls. Conclusions: Results demonstrate +Epi improves mitochondrial function, reduces OS and inflammation in the hippocampus and cortex leading to improved short- and long-term memory in aged animals providing evidence for possible mechanisms of action. Full article

Prenatal ethanol exposure (PEE) alters fetal brain development, potentially increasing the risk of neurodegenerative diseases such as Alzheimer’s disease (AD) later in life. Although glial activation is implicated in AD pathology via cannabinoid and neuroinflammatory signaling, its potential response to PEE in the developing brain and its contribution to AD pathogenesis remain unknown. Using 3×Tg-AD offspring of both sexes born to mothers with PEE, we analyzed astrogliosis, inflammatory markers, and key components of cannabinoid and Ca²⁺ signaling in primary cultures of hippocampal astrocytes, elements whose dysfunction contributes to neurodegeneration. Our results indicated that PEE increased astrogliosis/inflammatory response (significant elevation of Gfap and Tnfα expression) in hippocampal astrocytes at birth. This neuroinflammation was significantly associated with lower expression of cannabinoid receptors (Cnr1 and Gpr55), and decreased concentrations of the anti-inflammatory lipid PEA in the culture medium, probably due to a deregulated endocannabinoid enzymatic machinery (NAPE-PLD/FAAH ratio). This research provides insights into GRP55/PEA-mediated signaling as a potential hippocampal astrocytic mechanism influenced by maternal ethanol exposure, which may contribute to neurobiological changes associated with increased vulnerability to AD-related pathology. Full article