Frontiers in Neuroscience最新文献

Background: Obese patients have worse outcomes after surgery and are at increased risk for perioperative neurocognitive disorders (PND). Our aim was to detail the cognitive trajectories of patients undergoing bariatric surgery (BS) and map distinct structural brain changes using magnetic resonance imaging (MRI) to better understand the association between the vulnerable brain, surgery, and the arc of PND.

Methods: Prospective pilot study with longitudinal comprehensive cognitive assessments and MRI were performed on obese patients scheduled for BS. We analyzed baseline cognitive function and high-resolution T1-/T2-weighted brain images on 19 obese patients [age, 54 (9) years, BMI, 40 (36, 42) kg m^-2] and compared with 50 healthy control subjects [age, 52 (6) years; BMI, 25 (24, 27) kg m^-2]. Patients were evaluated within five days of BS (baseline), immediately after (within 48h), and follow up at six months.

Results: At baseline, obese patients had significant brain tissue changes seen in MRI and decreased cognitive scores compared to controls (MoCA 26 vs 28, P = 0.017). Surgery induced further gray matter volume and brain tissue changes along with reduced cognitive scores within the immediate postoperative period (MoCA 26 vs 24, P < 0.001). At six months, we observed reversal of brain alterations for most patients and a concomitant rebound of cognitive scores to patient's baseline status.

Conclusions: Bariatric surgery resulted in worsening of preexisting brain structural integrity and lower cognitive function for obese patients compared to baseline. These distinct brain lesions are consistent with specific domains of cognition. Most of these changes reverted to patient's baseline condition within six months after surgery.

[This corrects the article DOI: 10.3389/fnins.2021.823550.].

[This corrects the article DOI: 10.3389/fnins.2024.1439155.].

Background: Melatonin (MLT) and its receptor deficiency have been shown to be associated with type 2 diabetes mellitus (T2DM). Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive alternative intervention for patients suffering from hyperglycemia. Here, we aimed to investigate the role of taVNS on blood glucose modulation via intestinal melatonin receptors (MRs) and MLT secretion in hyperglycemia.

Methods: Adult male Zucker diabetes fatty (ZDF) rats and Zucker lean (ZL) littermates were used. Forty ZDF rats were randomized into ZDF, taVNS, Px + taVNS and Lu + Px + taVNS groups (Px: pinealectomy, Lu: Luzindole). ZL rats served as a control group for comparison with ZDF rats without involvement in the taVNS intervention. Thirty min-taVNS interventions (2/15 Hz, 2 mA, 30 min/days) were administered once daily under anesthesia for 3 consecutive weeks in taVNS, Px + taVNS and Lu + Px + taVNS groups. Body weight and fasting blood glucose (FBG) were measured weekly in all rats, and real-time blood glucose was tested in the ZL and ZDF groups before, during and after the taVNS intervention. Plasma MLT concentration and the expression of MRs in the duodenum, jejunum and ileum were measured by the end of experiments.

Results: Compared with the ZL group, the level of FBG and body weight increased (all p < 0.01), plasma MLT secretion and the expression of MRs in duodenum, jejunum and ileum of ZDF rats decreased obviously (all p < 0.05), respectively. TaVNS can significantly reverse the hyperglycemia by regulating the non-pineal-derived MLT and MRs system in Px + taVNS group. Compared with the ZDF group, the expression of different intestinal MRs in the taVNS group was increased and more compactly arranged (both p < 0.05), the level of plasma MLT secretion was up-regulated (p < 0.01), and FBG and body weight were decreased (both p < 0.01). Meanwhile, after taVNS intervention in rats in the Px + taVNS group, we observed an increase in MLT secretion and the number of intestinal MRs compared with the taVNS group (all p > 0.05). In contrast, ZDF rats in which the pineal gland was excised by taVNS intervention and injected with the MRs antagonist Luzindole did not show these changes.

Conclusion: The glucose reduction effect of taVNS may be related to regulating MLT levels and expressing intestinal MRs.

Introduction: Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) experience cognitive problems with attention, information processing speed, working memory, learning efficiency, and executive function. Commonly, patients report worsening of cognitive symptoms over time after physical and/or cognitive challenges. To determine, monitor, and manage longitudinal decrements in cognitive function after such exposures, it is important to be able to screen for cognitive dysfunction and changes over time in clinic and also remotely at home. The primary objectives of this paper were: (1) to determine whether a brief computerized cognitive screening battery will detect differences in cognitive function between ME/CFS and Healthy Controls (HC), (2) to monitor the impact of a full-day study visit on cognitive function over time, and (3) to evaluate the impact of exercise testing on cognitive dysfunction.

Methods: This cognitive sub-study was conducted between 2013 and 2019 across seven U.S. ME/CFS clinics as part of the Multi-Site Clinical Assessment of ME/CFS (MCAM) study. The analysis included 426 participants (261 ME/CFS and 165 HC), who completed cognitive assessments including a computerized CogState Brief Screening Battery (CBSB) administered across five timepoints (T0-T4) at the start of and following a full day in-clinic visit that included exercise testing for a subset of participants (182 ME/CFS and 160 HC). Exercise testing consisted of ramped cycle ergometry to volitional exhaustion. The primary outcomes are performance accuracy and latency (performance speed) on the computerized CBSB administered online in clinic (T0 and T1) and at home (T2-T4).

Results: No difference was found in performance accuracy between ME/CFS and HCs whereas information processing speed was significantly slower for ME/CFS at most timepoints with Cohen's d effect sizes ranging from 0.3-0.5 (p < 0.01). The cognitive decline over time on all CBSB tasks was similar for patients with ME/CFS independent of whether exercise testing was included in the clinic visit.

Conclusion: The challenges of a clinic visit (including cognitive testing) can lead to further cognitive deficits. A single short session of intense exercise does not further reduce speed of performance on any CBSB tasks.

Introduction: Gliomas are the most prevalent primary malignant intracranial tumors, characterized by high rates of therapy resistance, recurrence, and mortality. A major factor contributing to the poor prognosis of gliomas is their ability to diffusely infiltrate surrounding and even distant brain tissues, rendering complete total resection almost impossible and leading to frequent recurrences. The extracellular matrix (ECM) plays a key role in the tumor microenvironment and may significantly influence glioma progression, recurrence, and therapeutic response.

Methods: In this study, we first identified the ECM and the Versican (VCAN), a key ECM protein, as critical contributors to glioma recurrence through a comprehensive analysis of transcriptomic data comparing recurrent and primary gliomas. Using single-cell sequencing, we revealed heterogeneous distribution patterns and extensive intercellular communication among ECM components. External sequencing and immunohistochemical (IHC) staining further validated that VCAN is significantly upregulated in recurrent gliomas and is associated with poor patient outcomes.

Results: Functional assays conducted in glioma cell lines overexpressing VCAN demonstrated that VCAN promotes cell proliferation and migration via the PI3K/Akt/AP-1 signaling pathway. Furthermore, inhibiting the PI3K/Akt pathway effectively blocked VCAN-mediated glioma progression.

Conclusion: These findings provide valuable insights into the mechanisms underlying glioma recurrence and suggest that targeting both VCAN and the PI3K/Akt pathway could represent a promising therapeutic strategy for managing recurrent gliomas.

Background: Several heart rate variability (HRV) parameters were reported to be associated with residual renal function (RRF) in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). However, it is unclear whether using HRV or other autonomic nervous system (ANS) activity indexes can predict RRF decline in CAPD patients.

Methods: Patients undergoing CAPD in 2022 from the First Affiliated Hospital of Nanjing Medical University were enrolled in this study. Their clinical characteristics, 5-min HRV parameters and average voltage of 5-min skin sympathetic nerve activity (aSKNA) were collected. According to the 12-month glomerular filtration rate (GFR) decline rate compared with the upper quartile, these patients were categorized into two groups: RRF decline (RRF-D) group and RRF stable (RRF-S) group. Clinical factors and ANS activity indexes for predicting 1-year RRF decline were analyzed using logistic regression, and a nomogram model was further established. The relationships between volume load related indexes and aSKNA were displayed by Spearman's correlation graphs.

Results: Ninety-eight patients (53 women, average age of 46.7 ± 13.0 years old) with a median dialysis vintage of 24.5 months were enrolled in this study. Seventy-three patients were categorized into the RRF-S group and 25 patients into the RRF-D group. Compared with RRF-S group, patients in the RRF-D group had higher systolic blood pressure (BP; p = 0.019), higher GFR (p = 0.016), higher serum phosphorous level (p = 0.030), lower total Kt/V (p = 0.001), and lower levels of hemoglobin (p = 0.007) and albumin (p = 0.010). The RRF-D group generally exhibited lower HRV parameters and aSKNA compared with the RRF-S group. A nomogram model included clinical factors (sex, systolic BP, hemoglobin, GFR, and total Kt/V) and aSKNA showed the largest AUC of 0.940 (95% CI: 0.890-0.990) for predicting 1-year RRF decline.

Conclusion: The nomogram model included clinical factors (sex, systolic BP, hemoglobin, GFR and total Kt/V) and ANS activity index (aSKNA) might be a promising tool for predicting 1-year RRF decline in CAPD patients.

The prevalence of neurodegenerative disorders such as Parkinson's disease are increasing as world populations age. Despite this growing public health concern, the precise molecular and cellular mechanisms that culminate in neurodegeneration remain unclear. Effective treatment options for Parkinson's disease and other neurodegenerative disorders remain very limited, due in part to this uncertain disease etiology. One commonality across neurodegenerative diseases is sustained neuroinflammation, mediated in large part by microglia, the innate immune cells of the brain. Initially thought to simply react to neuron-derived pathology, genetic and functional studies in recent years suggest that microglia play a more active role in the neurodegenerative process than previously appreciated. Here, we review evidence for the roles of microglia in Parkinson's disease pathogenesis and progression, with a particular focus on microglial functions that are perturbed by disease associated genes and mutations.