Fibromyalgia (FM) is a complex, chronic disorder characterized by widespread pain, fatigue, cognitive impairment, and sleep disturbances, and it is considered the second most prevalent rheumatic condition. Current pharmacological therapies are often associated with undesirable side effects, underscoring the need for safer, natural therapeutic alternatives. Moringa oleifera leaves are rich in nutrients and bioactive antioxidants and have demonstrated therapeutic potential in inflammatory and immune-related disorders. This study investigated the therapeutic effects of M. oleifera leaf extract in a reserpine-induced fibromyalgia model using multiple treatment groups of male mice. Behavioral, histological, and neurochemical assessments were conducted. Mice with reserpine-induced FM exhibited reduced body weight, decreased paw withdrawal threshold and thermal latency, diminished locomotor activity and grooming behavior, impaired spontaneous alternation, and prolonged immobility time. Histopathological examination revealed marked structural disruption of hippocampal tissue, accompanied by reduced serotonin levels and elevated concentrations of IL-1β, TNF-α, and NO compared with control animals. Treatment with M. oleifera significantly attenuated these alterations by improving behavioral performance, restoring hippocampal architecture, and normalizing serotonin levels and pro-inflammatory markers. These findings indicate that M. oleifera exerts a protective effect against reserpine-induced fibromyalgia, likely through modulation of serotonergic activity and suppression of inflammatory cytokine signaling pathways.
[This corrects the article DOI: 10.1016/j.ibneur.2022.06.006.].
Alzheimer's disease (AD) is a multifactorial neurodegenerative disease. Identifying early diagnostic biomarkers are crucial for improving the accuracy and timeliness of the disease diagnosis and prognostication. Emerging evidence links metabolic dysregulation to AD pathogenesis. We evaluated serum metabolites and their association with regional brain hypometabolism measured using fluorodeoxyglucose positron emission tomography (FDG‑PET). We studied 892 participants using the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, including 286 cognitively normal (CN) individuals, 468 patients with mild cognitive impairment (MCI), and 138 with AD who had a complete baseline FDG‑PET and serum metabolomics data. After outlier removal and adjustment for age, sex, and years of education, we tested linear associations between individual metabolite levels and glucose standardized uptake value ratio (SUVR) as a measure of brain metabolism within predefined regions of interest (ROIs). In the AD group, higher levels of hydroxyproline (β = 0.24, P = 0.005) and aspartate (β = 0.17, P = 0.047) were associated with greater FDG SUVR prior to adjustment, although the association with aspartate did not remain significant after FDR correction. In the MCI group, higher levels of putrescine (β = -0.12, P = 0.010) and glutamine (β = -0.11, P = 0.019) were related to lower FDG SUVR prior to adjustment but lost significance after correction. In CN participants, higher levels of ornithine were associated with greater FDG SUVR (β = 0.13, P = 0.030) prior to adjustment. Our findings suggest that specific serum metabolites show differential associations with regional brain glucose hypometabolism in patients across the AD continuum. While these associations did not remain significant after correction for multiple testing, preliminary signals linking amino acid-related metabolites (e.g., hydroxyproline, aspartate, putrescine, glutamine, and ornithine) to brain metabolism highlight the potential role of metabolic pathways in AD pathophysiology. These results support the utility of metabolomics as a complementary approach for identifying early biomarkers of neurodegeneration.
Epilepsy affects 1.2 % of the US population, with one-third of cases being drug-resistant. Magnesium modulates neuronal excitability, and dietary insufficiency may elevate seizure risk. Systemic inflammation, quantified by the Composite Dietary Antioxidant Index (CDAI), represents a plausible mediator, but population-level evidence remains limited. To investigate associations between dietary magnesium intake and epilepsy prevalence, assess CDAI-mediated pathways, and identify high-benefit subgroups. Cross-sectional analysis included 33,486 adults (≥20 years) from NHANES 2013-2018. Dietary magnesium intake was derived from two 24-hour recalls and analyzed continuously (per SD) and categorically (quartiles). Epilepsy was self-reported. CDAI integrated six micronutrient intakes. Weighted multivariable logistic regression evaluated magnesium-epilepsy associations, adjusted for sociodemographic, clinical, and dietary covariates. Mediation analysis quantified CDAI's role. After full adjustment, each SD increase in magnesium intake was associated with 62 % lower epilepsy prevalence (OR = 0.38, 95 % CI: 0.21-0.70, p = 0.004). Quartile analysis revealed a significant inverse trend (p-trend = 0.032), with Q4 (highest intake) exhibiting the lowest risk (OR = 0.38, 95 % CI: 0.12-1.15). CDAI mediated 50.1 % of magnesium's protective effect (indirect effect: -0.478, 95 % CI: -1.031 to -0.166; p < 0.001). Stronger inverse associations occurred in Non-Hispanic Black (OR = 0.32, 95 % CI: 0.11-0.94) and Mexican American (OR = 0.35, 95 % CI: 0.16-0.76) individuals (p-interaction = 0.009) and those with obesity (OR = 0.26, 95 % CI: 0.10-0.68). Higher dietary magnesium intake is associated with significantly reduced epilepsy prevalence in US adults, with half of this effect mediated by attenuated inflammation (CDAI). Populations with elevated inflammation burdens or socioeconomic disadvantages may derive particular benefit. These findings support magnesium-rich diets as a potential preventive strategy and warrant prospective validation.
Stress contributes to neuropsychiatric disorders by altering brain circuits and neurotransmitter signaling, often in a sex-dependent manner. The specifics of these stress-induced changes and their role in the development and perseverance of conditions like depression are largely unknown. We examined how context discrimination and neurotransmitter co-expression in the medial septum (MS) changes in response to unpredictable chronic mild stress (uCMS). Female mice subjected to uCMS showed significant context discrimination impairments compared to female controls, while male mice showed no differences in context discrimination as a result of uCMS. We conducted immunolabeling in the MS and found that in females, uCMS reduced the number of cholinergic (ChAT+) neurons while increasing the percent of neurons co-expressing ChAT & GAD67 (marker for GABAergic neurons). These changes suggest a link between chronic stress, neurotransmitter phenotype plasticity in the MS, and hippocampal dysfunction. These differences were observed in the absence of changes to apoptosis and overall neuron number and were specific to female mice; no significant changes to MS neurotransmitter expression was observed in males. Our future work will focus on further dissecting the specific molecular mechanisms behind these changes.
Multifocal motor neuropathy (MMN) is a rare immune-mediated neuropathy characterized by motor nerve involvement and, typically, a good response to intravenous immunoglobulin (IVIg). However, a subgroup of patients shows poor or absent treatment response and a more rapid disease course. We aim to characterize clinical, laboratory, and electrophysiological features associated with IVIg response in MMN over a follow-up period of up to 20 years. Thirteen patients fulfilling diagnostic criteria for definite MMN were retrospectively analyzed. Detailed clinical data, comorbidities, IVIg treatment regimens, and serial nerve conduction studies (NCS) were evaluated. Particular attention was given to the extent and distribution of conduction block (CB) and temporal dispersion (TD). IVIg response was defined as ≥ 1-point improvement in MRC strength in at least two muscle groups within 4 weeks after infusion or equivalent functional improvement documented in medical records. Four of 13 patients (31%) showed poor or absent IVIg response. These patients exhibited a higher number of clinically and electrophysiologically affected motor nerves at disease onset (median 6 vs. 3, p = 0.014) and more nerves with TD (median 2.5 vs. 1, p = 0.025), compared to IVIg responders. CB alone did not reliably distinguish responders from non-responders (median 1 vs. 1, p = 0.74). Anti-GM1 IgM antibodies were detected in 44% of the patients tested, of whom 75% were non-responders. Comorbidities (e.g., diabetes II, malignancy, autoimmune disease) were more frequent among non-responders. A pattern of early nerve involvement with prominent TD appears to be associated with a more aggressive disease course and poorer IVIg response. Diagnostic evaluation in MMN should not focus solely on focal CB but also systematically assess the number of nerves with TD. Prospective studies with standardized protocols are needed to validate these findings.
Approximately 20-30% of ischemic stroke patients with small artery occlusion (SAO) experience early neurological deterioration (END) after stroke onset, which is associated with a poor prognosis. Our aim was to determine the predictive ability of quantitative susceptibility mapping (QSM) for END in patients with SAO. As neurological deficits, the National Institutes of Health Stroke Scale (NIHSS) was used. END was defined as an increase of ≥ 2 points on the NIHSS from baseline during the first week. 126 SAO stroke participants within 24 h of stroke onset were included in this study and divided into END group and nEND (no early neurological deterioration) group. QSM values were calculated from magnetic resonance imaging (MRI) data and clinical characteristics were collected. A cluster-based permutation test was conducted between groups and diagnostic efficacy of the QSM value was evaluated. As a result, END group showed a different cortical susceptibility pattern compared with nEND group. Specifically, END group showed higher QSM value in the left/right precentral gyrus, the middle frontal gyrus, the opercular part of the left/right inferior frontal gyrus, the triangular part of left inferior frontal gyrus and postcentral gyrus, while lower in the dorsolateral part of left superior frontal. The support vector machine (SVM) classifier's analysis showed a high power for QSM diagnostic efficacy between END and nEND groups. In addition, homocysteine (Hcy), low-density lipoprotein (LDL), and total cholesterol (TC) were correlated with QSM values in some specific brain regions. The cluster-based permutation test indicated the differences of brain QSM value distribution between END and nEND groups. The SVM classifier's analysis showed a high power for QSM diagnostic efficacy between the two groups. Our study revealed the underlying predictive value of QSM in END of SAO stroke patients.
Prediabetes is a serious health condition characterized by blood glucose levels that are higher than normal but not high enough for a diagnosis of type 2 diabetes. It remains unclear whether alterations in cortical morphology occur during the prediabetic stage. This study aimed to investigate changes in cortical thickness and gyrification in individuals with prediabetes, and to explore whether these changes can predict cognitive performance using a machine learning approach. T1-weighted MRI scans were acquired from 48 patients with prediabetes and 42 healthy controls. Surface-based morphometric analyses, including cortical thickness and the local gyrification index (LGI), were performed using FreeSurfer. Group comparisons were conducted. Neuropsychological assessments included the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), and the Trail Making Test (TMT) Parts A and B. Pearson correlation analyses were conducted to examine associations between morphometric changes and cognitive performance. Furthermore, PyCaret, a machine learning framework, was applied to evaluate the predictive power of cortical features and clinical variables in predicting cognitive performance. Compared with controls, individuals with prediabetes exhibited significantly reduced cortical thickness in the left inferior temporal gyrus (ITG) and decreased LGI in the left precentral gyrus. TMT-A and TMT-B scores were significantly higher in the prediabetes group, indicating poorer cognitive performance. Cortical thickness in the left ITG was negatively correlated with TMT-B performance (r = -0.54, 95 % CI: -0.71 to -0.31, p = 0.0001). Machine learning analysis identified the Extreme Gradient Boosting classifier as the best-performing model (AUC = 0.87, accuracy = 0.80). Our findings suggest that cortical alterations in the ITG and precentral gyrus are evident during the prediabetic stage and relate to early cognitive dysfunction. These results highlight the potential of combining neuroimaging biomarkers and AI models for early detection and intervention in prediabetes-associated cognitive decline.
Objectives：Serum exosomal miRNAs are promising biomarkers and therapeutic targets for multiple diseases, but their expression profiles and functions in acute ischemic stroke (AIS) remain unclear. This study aimed to clarify the expression characteristics of serum exosomal miRNAs in AIS and explore the regulatory roles of key miRNAs in AIS progression.Methods：We first detected serum exosomal miRNA expression profiles of AIS patients and healthy controls via RNA-seq, then validated candidate miRNA levels using qRT-PCR. Enzyme-linked immunosorbent assay (ELISA) was employed to measure serum levels of antithrombotic proteins [thrombomodulin (TM), endothelial NO synthase (eNOS), tissue plasminogen activator (t-PA)]. The regulatory effects of differentially expressed miRNAs on these proteins were verified in human umbilical vein endothelial cells (HUVEC) via transfection assays. Statistical analyses were performed using SPSS 26 and GraphPad Prism 8.Results：Compared with healthy controls, AIS patients exhibited significantly decreased serum exosomal levels of miR-23a-3p, miR-375-3p, and miR-122-5p, along with elevated serum TM, eNOS, and t-PA levels. miR-23a-3p and miR-375-3p could modulate the expression of TM, eNOS, and t-PA in HUVEC, and this regulatory relationship may be direct or indirect. The combination of these miRNAs and proteins achieved moderate predictive efficacy for AIS occurrence.Discussion：This study identifies serum exosomal miR-23a-3p and miR-375-3p as potential biomarkers for AIS and reveals their regulatory role in antithrombotic protein expression, providing novel insights into AIS's molecular mechanism and diagnostic strategies.
Post-traumatic stress disorder (PTSD) is associated with cognitive impairments, neuroendocrine dysregulation, and hippocampal neuronal loss. Although exercise has shown therapeutic potential in stress-related conditions, comparative evidence on voluntary versus forced exercise modalities in animal models of PTSD remains limited. This study evaluated the effects of voluntary (running wheel, RW) and forced (treadmill running, TR) exercise on cognitive performance, thyroid function, and hippocampal integrity in a rat model of PTSD induced by single prolonged stress (SPS). Male Wistar rats were randomly assigned to non-stressed or SPS-exposed groups, each further subdivided into sedentary, voluntary exercise, or forced exercise subgroups (n = 7 per group). Cognitive performance was assessed using the Object Location Memory Test and Object Recognition Memory Test. Serum levels of T3, T4 and TSH were measured using ELISA kits. Hippocampal neuronal density was evaluated via hematoxylin and eosin staining. SPS exposure significantly impaired spatial and recognition memory, disrupted thyroid hormone profiles (decreased T3 and T4, increased TSH), and reduced hippocampal neuronal density in sedentary rats. Both RW and TR interventions improved cognitive function, normalized thyroid hormone levels, and preserved hippocampal structure. Notably, voluntary exercise produced greater improvements in memory performance and endocrine recovery compared to forced exercise. Both voluntary and forced exercise alleviate cognitive, hormonal, and structural impairments in a rat model of PTSD, with voluntary exercise demonstrating superior therapeutic efficacy. These findings highlight the potential of physical activity, particularly self-directed, voluntary modalities, as a promising non-pharmacological strategy for mitigating the neurobiological consequences of traumatic stress.
Neurodegenerative diseases, such as Alzheimer's disease (AD), are characterized by oxidative imbalance, leading to memory deficits and cognitive impairments. Aluminium chloride (AlCl3), a neurotoxin found in certain foods and medications, disrupts neurotransmitter systems, thereby exacerbating cognitive decline. Current drug development strategies aim to counter these effects through cholinesterase inhibition, activation of GABAergic transmission, the use of antioxidants, and the promotion of neuroprotection. This work was conducted to assess the neuroprotective properties of the aqueous extract of Linzia gerberiformis (L. gerberiformis) leaves against AlCl3 induced cognitive impairment in mice. AlCl3 (70 mg/kg) was administered orally in mice to induced memory loss a core feature of Alzheimer Disease. Mice were pretreated with aqueous extract of L. gerberiformis leaves (75, 150 and 300 mg/kg) for six weeks, and memory integrity was assessed using the object location test (OLT) and the T-Maze test. One hour after completion of the T-Maze, the mice were sacrificed, the hippocampus and prefrontal cortex were then collected to assess the cholinergic (acetylcholinesterase (AChE) and acetylcholine (ACh)), GABAergic systems and oxidative stress (nitric oxide (NO), malondialdehyde (MDA) SOD, Catalase (CAT), reduced glutathione (GSH)). The aqueous extract of L. gerberiformis leaves demonstrated significant effects (P < 0.01 and P < 0.05) at doses of 75 and 150 mg/kg in improving short-term learning memory, as well as a significant enhancement (P < 0.05) of long-term spatial memory on day 3 at the dose of 75 mg/kg. AlCl3 (70 mg/kg) induced increase in AChE (P < 0.05; P < 0.01), NO (P < 0.05; P < 0.001), and MDA (P < 0.05; P < 0.01), while decreasing ACh (P < 0.01), GABA (P < 0.05; P < 0.01), SOD (P < 0.01; P < 0.001), CAT (P < 0.05), and GSH (P < 0.01) in the hippocampus and prefrontal cortex. Pretreatment with aqueous extract of L. gerberiformis leaves significantly restored these parameters (P < 0.01; P < 0.001) for Ach at the doses 75 and 150 mg/kg and GABA (P < 0.05) at all doses. Significant improvement was also observed for SOD (P < 0.05 and P < 0.01), GSH, and MDA (P < 0.05 and P < 0.01), as well as for NO (P < 0.05 and P < 0.01) in both the hippocampus and prefrontal cortex. The present study established that the aqueous extract of L. gerberiformis leaves ameliorated AlCl3-induced neurotoxicity by modulating the activation of the cholinergic, GABAergic and antioxidant pathways.
Spinal cord injury (SCI) is a severe neurological disorder that leads to significant complications, including loss of bladder/bowel control and increased infection risk. The current standard treatment involves methylprednisolone administration and surgical decompression, but finding an effective therapy with minimal side effects remains a major challenge. This study aimed to investigate the effects of an optimized conditioned medium derived from rat adipose-derived mesenchymal stem cells (AD-MSCs) and dihydroepiandrosterone (DHEA) on behavioral indices, oxidative stress, stereological parameters, and histopathological outcomes in rats with compressive spinal cord injury (SCI). In this study, 60 adult female rats were randomly divided into five groups: Sham group (laminectomy + intraperitoneal injection of 1 % dimethyl sulfoxide [DMSO], 200 µL for seven consecutive days), SCI-induced group (SCI induction + intraperitoneal injection of 1 % DMSO, 200 µL for seven consecutive days), Treatment group 1 (SCI induction + intraperitoneal injection of DHEA [30 mg/kg] dissolved in 1 % DMSO for seven consecutive days), Treatment group 2 (SCI induction + intraperitoneal injection of conditioned medium [200 µL] for seven consecutive days), Treatment group 3 (SCI induction + intraperitoneal injection of DHEA [30 mg/kg] dissolved in 1 % DMSO followed by conditioned medium [200 µL] for seven consecutive days). Behavioral assessments were performed using the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and the rotarod test. Additionally, the levels of antioxidant enzymes-catalase, glutathione (GSH), superoxide dismutase (SOD), and the lipid peroxidation marker malondialdehyde (MDA)-were measured using respective assay kits. For stereological evaluation (to estimate neuronal and non-neuronal cell counts, gray and white matter volumes, spinal cord volume, and lesion area) and histopathological assessment (to evaluate inflammation, necrosis, and hemorrhage indices), tissue samples were stained with Cresyl Violet. The findings revealed that in the SCI-induced group, motor function, neuronal cell number in spinal gray matter, non-neuronal cell number in the spinal cord, white and gray matter volumes, total spinal cord volume, and levels of catalase, GSH, and SOD were significantly reduced compared to the sham group. Conversely, the spinal lesion volume and MDA levels were elevated. Treatment with DHEA, AD-MSC-conditioned medium, or their combination reversed these effects. Notably, the combined treatment group exhibited more pronounced therapeutic improvements compared to monotherapy groups. The administration of DHEA and AD-MSC-conditioned medium, particularly in combination, appears to enhance motor function, elevate antioxidant enzyme activity, reduce lipid peroxidation, improve spinal cord structural parameters (volume and cell counts), and ameliorate pathological markers in an animal model of compressive SCI.
The underlying mechanisms of cognitive impairment in patients with white matter hyperintensities (WMHs) remain largely elusive. Glymphatic dysfunction, as measured by the diffusion tensor imaging along the perivascular space (DTI-ALPS) index, has been associated with cognitive decline across various neurological and psychiatric disorders. This study aims to examine the potential association between glymphatic dysfunction, as measured by the DTI-ALPS index, and cognitive impairment in patients with WMHs. A total of 88 patients with varying degrees of WMHs (Mild = 25, Moderate = 34, Severe = 29) and 32 matched healthy controls were recruited. Comprehensive neuropsychological assessments and MRI scans were performed on all participants. We compared demographic information, cognitive function, and DTI-ALPS indices between patients with WMHs and controls, and evaluated the correlation between cognitive impairment and the DTI-ALPS index. Apart from hypertension, demographic characteristics were comparable across the four groups. Patients with WMHs showed significant impairments in emotional status, global function, language function, memory function, processing speed and cognitive flexibility. A reduction in Left_ALPS, Right_ALPS, and Mean_ALPS was observed in patients with WMHs, with these decreases significantly and negatively correlated with the WMHs volume (Left_ALPS, R = -0.381, P FDR < 0.001; Right_ALPS, R = -0.423, P FDR < 0.001; and Mean_ALPS, R = -0.476, P FDR < 0.001). After FDR correction, Mean_ALPS remained significantly correlated with language function (S-VFT: R = 0.338, P FDR = 0.030), while trends were observed between Mean_ALPS and emotional status, global function, memory function, and processing speed. Cognitive impairment in patients with WMHs is closely linked to decreased DTI-ALPS index, especially as white matter lesions worsen. Glymphatic dysfunction may play a critical role in this cognitive impairment, positioning the DTI-ALPS index may serve as a potential biomarker for cognitive impairment in patients with WMHs.
The diving response is a cardiorespiratory reflex characterized by apnea, bradycardia and increased peripheral vascular resistance when animals submerge underwater. Afferent information initiating this reflex response projects from the nasal mucosa via trigeminal nerves to activate second-order afferent neurons within the medullary dorsal horn (MDH). The present study investigated the synapse between these trigeminal nerves and MDH neurons, specifically what neurotransmitter receptors are expressed by MDH neurons activated during diving. Male Sprague-Dawley rats were trained to dive repetitively through an underwater maze, and Fos was used as a measure of neuronal activation. Immunohistochemistry combined with epifluorescent microscopy was used to determine which ionotropic glutamate receptor subunits, or if the Substance P receptor NK-1, were co-expressed by activated MDH neurons. Results indicate repetitive diving primarily activates small oval-shaped MDH neurons, and these Fos-positive MDH neurons co-express AMPA glutamate receptor subunits GluA1 and GluA2/3, KA glutamate receptor subunit GluK5, and NMDA glutamate receptor subunit GluN1. Since these subunits are constituent parts of their respective receptor structure, these findings reveal the formation of AMPA, KA, and NMDA glutamate receptors on the cellular membrane of these activated MDH neurons. In addition, MDH neurons activated by repetitive diving co-express the Substance P receptor NK-1. This research indicates that MDH neurons activated by diving express neurotransmitter receptors for both glutamate and SP. This supports the assertion that trigeminal nerves innervating the nasal passages release glutamate and SP within their central synapses in the brainstem and can function as part of the afferent limb of a cardiorespiratory reflex.
Radiation-induced temporal lobe injury (RI-TLI) is one of the most common late-stage complications after radiotherapy for nasopharyngeal carcinoma (NPC), which seriously affects patients' cognitive function and quality of life. However, the mechanism by which RI-TLI affects the gray matter (GM) and white matter (WM) across the whole brain, leading to cognitive impairment, is currently unclear in NPC patients. One year after the end of radiotherapy, 32 NPC patients with RI-TLI (RI-TLI group) and 38 NPC patients without RI-TLI (nRI-TLI group) were included in this study. The Montreal Cognitive Assessment (MoCA) was applied to evaluate the differences of cognitive function between RI-TLI and nRI-TLI groups. In addition, T1 structural magnetic resonance imaging data were acquired, and then the whole-brain voxel-based morphometry was employed to compare the differences of GM and WM between groups. The relationships between GM and WM of abnormal brain regions and MoCA scores were explored. Finally, receiver operating characteristic (ROC) curve was performed to determine the suitability of altered brain structure for distinguishing RI-TLI from nRI-TLI. Compared with nRI-TLI group, RI-TLI group exhibited decreased attention, delayed recall scores and total scores of MoCA. In addition, RI-TLI group exhibited decreased GM volume in the right middle temporal gyrus, left hippocampus, right superior temporal gyrus, right superior frontal gyrus and decreased GM density in the left superior frontal gyrus, right superior frontal gyrus, right supplementary motor area. Moreover, RI-TLI group demonstrated decreased WM volume in the right inferior temporal gyrus, left hippocampus, right superior temporal gyrus, right medial superior frontal gyrus and decreased WM density in the left superior frontal gyrus, right superior frontal gyrus. The attention scores of MoCA were positively associated with GM volume of the right superior temporal gyrus, right superior frontal gyrus, GM density of the left superior frontal gyrus, right superior frontal gyrus, WM density of the left superior frontal gyrus. The delayed recall scores of MoCA were positively related to GM volume of the left hippocampus, WM density of the left superior frontal gyrus. The total scores of MoCA were positively associated with GM volume of the left hippocampus, WM volume of the left hippocampus, right superior temporal gyrus, WM density of the left superior frontal gyrus. ROC analysis demonstrated that altered GM and WM might be helpful for distinguishing RI-TLI from nRI-TLI. Compared to nRI-TLI patients, RI-TLI patients exhibit more severe cognitive impairment alongside decreased GM and WM in both the temporal lobe and prefrontal regions. The observed structural alterations are associated with the severity of cognitive deficits and may serve as potential neuroimaging markers for RI-TLI.
Sexual aggression and prenatal stress can exert profound intergenerational effects, disrupting maternal care and enhancing aggression in offspring via alterations to the hypothalamic-pituitary-adrenal (HPA) axis and related neurochemical systems. This study in Wistar rats examined the combined impact of male sexual aggression and prenatal stress on maternal caregiving behaviours, and the neurobiological mechanisms underlying sexually aggressive behaviours in male offspring (F1). Following exposure to sexual aggression, females were mated with group-housed or isolated males and assigned to prenatal stress or control conditions. Maternal care was quantified from postnatal day (PND) 2-8, while F1 male aggression was assessed in resident-intruder and sexual aggression paradigms. Neurochemical analyses measured arginine vasopressin (AVP), corticotropin-releasing hormone (CRH), serotonin, oxytocin, corticosterone, and neurokinin B in the prefrontal cortex, hippocampus, amygdala, and hypothalamus, alongside gene expression profiling. Prenatal stress significantly reduced maternal care-particularly nursing and licking-across PND 2-8, with deficits most pronounced when paired with paternal isolation. High-quality maternal care was associated with reduced F1 aggression, longer attack latencies, and lower CRHR1 expression in the hippocampus, suggesting a neuroprotective role. Prenatal stress increased CRHR1 expression in the amygdala and amplified aggression, anxiety-like behaviours, and reduced sociability. Serotonin correlated negatively with aggression and positively with non-social exploration, while corticosterone correlated positively with aggression. Oxytocin was linked to social behaviours, and CRH to exploratory behaviours, indicating distinct neuromodulatory pathways. These findings highlight the interactive effects of maternal and paternal environments on intergenerational behavioural programming and identify key neurochemical targets for mitigating stress-related aggression.
Obesity-related health issues, including cognitive decline linked to hippocampal neurogenesis and neuroplasticity, are gaining more attention as obesity rates rise worldwide. Physical activity is recognized as a potent stimulator of neurotrophic factors. This study examined the impact of six weeks of treadmill training on hippocampal molecular pathways in adult female Zucker diabetic fatty (obese) and Zucker lean rats. Animals were assigned to either treadmill exercise (n = 10) or sedentary control (n = 10) groups. Endurance training (ET) markedly upregulated mRNA expression of brain-derived neurotrophic factor and its receptor. The PI3K/Akt pathway was upregulated only in the trained lean rats and downregulated in the trained obese group compared with sedentary controls. ET elicited divergent effects on neurotrophin-associated PLCγ/PKC/CAMKII signalling between lean and obese groups. Sedentary obese rats primarily utilized the PLCγ/PKC axis, while both trained groups (lean and obese) showed increased CAMKII expression, associated with enhanced synaptic plasticity and memory. Enhanced synaptophysin mRNA indicated improved synaptogenesis and plasticity following ET. Trained obese rats also exhibited reduced expression of the microglial pro-inflammatory marker Iba1, alongside increased markers of oligodendrocyte regeneration and neurofilament expression. Behavioral assessment via the passive avoidance test demonstrated improved learning and memory in trained obese animals. Collectively, these findings suggest that ET may mitigate obesity-induced hippocampal damage, exert neuroprotection, and enhance hippocampal function.
The possible involvement of numerous chemical elements in the pathogenesis of neurodegenerative diseases has long been studied by researchers, yet no clear consensus regarding the concentration of Zinc (Zn) and the onset of Parkinson's disease (PD) has emerged. The objective of this study was to conduct a robust meta-analysis to clarify the association between Zn levels across different biological matrices and Parkinson's disease. A comprehensive literature search was conducted across six databases up to April 2024. We included 29 case-control studies reporting Zn concentrations in serum, plasma, and cerebrospinal fluid (CSF) and performed subgroup analyses by biological matrix, continent, and detection method to extend and update previous meta-analyses on this topic. Statistical meta-analysis was performed using STATA v18 software, calculating the weighted mean difference (WMD) and 95 % CIs using a random-effects REML model. Heterogeneity was assessed using the I2 statistic, and publication bias was tested using Begg's and Egger's tests. This meta-analysis pooled data from 29 unique studies. The analysis of Zn in serum (N=22 data points) revealed a statistically significant reduction in PD patients (WMD=-108.23 μg/L, 95% CI: [-205.27, -11.18], p=0.03), with extreme heterogeneity (I²=99.43%). A similar significant deficit was found in plasma (WMD=-258.15 μg/L, 95% CI: [-481.20, -35.11], p=0.02). In contrast, Zn levels in CSF (N=8 studies) showed no statistically significant overall difference (WMD=-15.88 μg/L, 95% CI: [-36.21, 4.46], p=0.13), exhibiting the highest heterogeneity (I2=99.91%). All pooled estimates were characterized by extremely high heterogeneity (I²>99 %), primarily driven by the Asian subgroup and methodological differences, indicating substantial between-study variability and the need for cautious interpretation. Begg's and Egger's tests did not suggest substantial publication bias in serum or plasma, but CSF findings should be interpreted with caution. Our research demonstrates a significant association between lower Zn levels in the peripheral circulation (serum and plasma) and susceptibility to PD, suggesting that Zn deficiency may contribute to oxidative stress in PD but without establishing a causal relationship. Our findings reiterate the necessity of large-scale longitudinal cohort studies to validate this association, address the issue of reverse causation, and rigorously evaluate whether correcting Zn deficiency has any therapeutic value in the prevention or progression of PD.
While the degree of population aging is increasing, a nationwide stroke program was started in 2011. We analyzed how population aging outpaced gains in stroke care in China. The number of deaths, incidence, prevalence, Disability-Adjusted Life Years (DALYs) attributable to stroke and its subtypes from 2012 to 2021 were extracted from the Global Health Data Exchange database. The total populations of age groups in 2012 and 2021 were extracted from the National Bureau of Statistics of China. The Das Gupta Decomposition method was applied to identify the contributions of population growth, population aging, and the changes in the incidence, mortality, prevalence, and DALYs. From 2012-2021, the total stroke incidence increased by 38.4 % (from 2.95 to 4.09 million), deaths by 17.6 % (from 2.20 to 2.59 million), and prevalence by 34.2 % (from 19.62 to 26.34 million) in China. Decomposition analysis identified rapid population aging as the predominant driver, accounting for 78.1 % of the incidence increase and even exceeding the total death increase (197.6 %), overwhelming the benefits from improved stroke care. The stroke subtype profile shifted markedly, with ischemic stroke's share of incidence rising from 62 % to 68 % and deaths from 41 % to 46 %, while intracerebral hemorrhage's contribution declined. The escalating stroke burden in China is primarily driven by population aging, followed by population growth, creating a paradox where healthcare improvements are offset demographically. The epidemic is increasingly characterized by ischemic stroke, leading to a growing population of survivors requiring long-term care. This necessitates a paradigm shift in health policy from a focus solely on reducing acute mortality towards building cost-effective, integrated systems for lifelong stroke management, chronic care, and secondary prevention tailored for an aging society.
An increasing number of neuroimaging studies have consistently indicated that the locus coeruleus is associated with cognitive impairment in the early stages of Alzheimer's disease, and the locus coeruleus plays a critical role in cognition, including memory encoding, consolidation, and retrieval. To investigate whether and how acupuncture modulates the functional connectivity patterns of the locus coeruleus, and offer a new perspective on the mechanism through which acupuncture exerts its efficacy. Resting-state functional magnetic resonance imaging (fMRI) data were collected from 50 patients with amnestic cognitive impairment (aMCI) before and after verum or sham acupuncture. Seed-based whole-brain functional connectivity (FC) was calculated and compared to explore the changing patterns of the locus coeruleus in aMCI patients following acupuncture. Increased FCs were observed between the left locus coeruleus and the left inferior parietal lobule, and between the right locus coeruleus and the right posterior cerebellum in aMCI patients after verum acupuncture. Further analyses revealed a correlation between FC of the left locus coeruleus and the left inferior parietal lobule before acupuncture and improvement in immediate recall in aMCI patients. These results suggest that acupuncture could enhance FC between the locus coeruleus and the inferior parietal lobule/the posterior cerebellum. These functional alterations appear to be linked to the efficacy of acupuncture, particularly in ameliorating memory deficits.