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Loss of cognitive function with age is devastating. EGL-30/GNAQ and Gαq signaling pathways are highly conserved between C. elegans and mammals, and murine Gnaq is enriched in hippocampal neurons and declines with age. We found that activation of EGL-30 in aged worms triples memory span, and GNAQ gain of function significantly improved memory in aged mice: GNAQ(gf) in hippocampal neurons of 24-month-old mice (equivalent to 70- to 80-year-old humans) rescued age-related impairments in well-being and memory. Single-nucleus RNA sequencing revealed increased expression of genes regulating synaptic function, axon guidance, and memory in GNAQ-treated mice, and worm orthologs of these genes were required for long-term memory extension in worms. These experiments demonstrate that C. elegans is a powerful model to identify mammalian regulators of memory, leading to the identification of a pathway that improves memory in extremely old mice. To our knowledge, this is the oldest age at which an intervention has improved age-related cognitive decline.

This study aimed to investigate the molecular mechanism under the pathophysiology of subarachnoid hemorrhage (SAH) and identify the potential biomarkers for predicting the risk of SAH. Differentially expressed mRNAs (DEGs), microRNAs, and lncRNAs were screened. Protein–protein interaction (PPI), drug–gene, and competing endogenous RNA (ceRNA) networks were constructed to determine candidate RNAs. The optimized RNAs signature was established using least absolute shrinkage and selection operator and recursive feature elimination algorithms. A total of 124 SAH-related DEGs were identified, and were enriched in inflammatory response, TNF signaling pathway, and others. PPI network revealed 118 hub genes such as TNF, MMP9, and TLR4. Drug–gene network revealed that chrysin targeted more genes, such as TNF and MMP9. JMJD1C-AS-hsa-miR-204-HDAC4/SIRT1 and LINC01144-hsa-miR-128-ADRB2/TGFBR3 regulatory axes were found from ceRNA network. From these networks, 125 candidate RNAs were obtained. Of which, an optimal 38 RNAs signatures (2 lncRNAs, 1 miRNA, and 35 genes) were identified to construct a Support Vector Machine classifier. The predictive value of 38 biomarkers had an AUC of 0.990. Similar predictive performance was found in external validation dataset (AUC of 0.845). Our findings provided the potential for 38 RNAs to serve as biomarkers for predicting the risk of SAH. However, their application values should be further validated in clinical.

Background: Postoperative cognitive dysfunction (POCD) is a common complication of the central nervous system in elderly surgical patients. Structural MRI and arterial spin labelling (ASL) techniques found that the grey matter volume and cerebral perfusion in some specific brain areas are associated with the occurrence of POCD, but the results are inconsistent, and the predictive accuracy is low. We hypothesised that the combination of cortical grey matter volumetry and cerebral blood flow yield higher accuracy than either of the methods in discriminating the elderly individuals who are susceptible to POCD after abdominal surgery. Materials and Methods: Participants underwent neuropsychological testing before and after surgery. Postoperative cognitive dysfunction (POCD) was defined as a decrease in cognitive score of at least 20%. ASL-MRI and T1-weighted imaging were performed before surgery. We compared differences in cerebral blood flow (CBF) and cortical grey matter characteristics between POCD and non-POCD patients and generated receiver operating characteristic curves. Results: Out of 51 patients, 9 (17%) were diagnosed with POCD. CBF in the inferior frontal gyrus was lower in the POCD group compared to the non-POCD group (p < 0.001), and the volume of cortical grey matter in the anterior cingulate gyrus was higher in the POCD group (p < 0.001). The highest AUC value was 0.973. Conclusions: The combination of cortical grey matter volumetry and cerebral perfusion based on ASL-MRI has improved efficacy in the early warning of POCD to elderly abdominal surgical patients. [ABSTRACT FROM AUTHOR]

Network neuroscience offers a unique framework to understand the organizational principles of the human brain. Despite recent progress, our understanding of how the brain is modulated by focal lesions remains incomplete. Resection of the temporal lobe is the most effective treatment to control seizures in pharmaco-resistant temporal lobe epilepsy (TLE), making this syndrome a powerful model to study lesional effects on network organization in young and middle-aged adults. Here, we assessed the downstream consequences of a focal lesion and its surgical resection on the brain's structural connectome, and explored how this reorganization relates to clinical variables at the individual patient level. We included adults with pharmaco-resistant TLE (n = 37) who underwent anterior temporal lobectomy between two imaging time points, as well as age- and sex-matched healthy controls who underwent comparable imaging (n = 31). Core to our analysis was the projection of high-dimensional structural connectome data—derived from diffusion MRI tractography from each subject—into lower-dimensional gradients. We then compared connectome gradients in patients relative to controls before surgery, tracked surgically-induced connectome reconfiguration from pre- to postoperative time points, and examined associations to patient-specific clinical and imaging phenotypes. Before surgery, individuals with TLE presented with marked connectome changes in bilateral temporo-parietal regions, reflecting an increased segregation of the ipsilateral anterior temporal lobe from the rest of the brain. Surgery-induced connectome reorganization was localized to this temporo-parietal subnetwork, but primarily involved postoperative integration of contralateral regions with the rest of the brain. Using a partial least-squares analysis, we uncovered a latent clinical imaging signature underlying this pre- to postoperative connectome reorganization, showing that patients who displayed postoperative integration in bilateral fronto-occipital cortices also had greater preoperative ipsilateral hippocampal atrophy, lower seizure frequency and secondarily generalized seizures. Our results bridge the effects of focal brain lesions and their surgical resections with large-scale network reorganization and interindividual clinical variability, thus offering new avenues to examine the fundamental malleability of the human brain. [ABSTRACT FROM AUTHOR]

Background: Losing one's only child is a major traumatic life event that may lead to post-traumatic stress disorder (PTSD); however, the underlying mechanisms of its psychological consequences remain poorly understood. Here, we investigated subregional hippocampal functional connectivity (FC) networks based on resting-state functional magnetic resonance imaging and the deoxyribonucleic acid methylation of the human glucocorticoid receptor gene (NR3C1) in adults who had lost their only child. Methods: A total of 144 Han Chinese adults who had lost their only child (51 adults with PTSD and 93 non-PTSD adults [trauma-exposed controls]) and 50 controls without trauma exposure were included in this fMRI study (age: 40–67 years). FCs between hippocampal subdivisions (four regions in each hemisphere: cornu ammonis1 [CA1], CA2, CA3, and dentate gyrus [DG]) and methylation levels of the NR3C1 gene were compared among the three groups. Results: Trauma-exposed adults, regardless of PTSD diagnosis, had weaker positive FC between the left hippocampal CA1, left DG, and the posterior cingulate cortex, and weaker negative FC between the right CA1, right DG, and several frontal gyri, relative to healthy controls. Compared to non-PTSD adults, PTSD adults showed decreased negative FC between the right CA1 region and the right middle/inferior frontal gyri (MFG/IFG), and decreased negative FC between the right DG and the right superior frontal gyrus and left MFG. Both trauma-exposed groups showed lower methylation levels of the NR3C1 gene. Conclusions: Adults who had lost their only child may experience disrupted hippocampal network connectivity and NR3C1 methylation status, regardless of whether they have developed PTSD. [ABSTRACT FROM AUTHOR]

Generalized tonic–clonic seizures (GTCS) are the severest and most remarkable clinical expressions of human epilepsy. Cortical, subcortical, and cerebellar structures, organized with different network patterns, underlying the pathophysiological substrates of genetic associated epilepsy with GTCS (GE‐GTCS) and focal epilepsy associated with focal to bilateral tonic–clonic seizure (FE‐FBTS). Structural covariance analysis can delineate the features of epilepsy network related with long‐term effects from seizure. Morphometric MRI data of 111 patients with GE‐GTCS, 111 patients with FE‐FBTS and 111 healthy controls were studied. Cortico‐striato‐thalao‐cerebellar networks of structural covariance within the gray matter were constructed using a Winner‐take‐all strategy with five cortical parcellations. Comparisons of structural covariance networks were conducted using permutation tests, and module effects of disease duration on networks were conducted using GLM model. Both patient groups showed increased connectivity of structural covariance relative to controls, mainly within the striatum and thalamus, and mostly correlated with the frontal, motor, and somatosensory cortices. Connectivity changes increased as a function of epilepsy durations. FE‐FBTS showed more intensive and extensive gray matter changes with volumetric loss and connectivity increment than GE‐GTCS. Our findings implicated cortico‐striato‐thalamo‐cerebellar network changes at a large temporal scale in GTCS, with FE‐FBTS showing more severe network disruption. The study contributed novel imaging evidence for understanding the different epilepsy syndromes associated with generalized seizures. [ABSTRACT FROM AUTHOR]