Biology subjects

Liu, Z.-Q.

Publications and source records attributed to Liu, Z.-Q..

26 records · Page 2Linked to original sources

bioRxiv2022

Spatially heterogeneous structure-function coupling in haemodynamic and electromagnetic brain networks

The relationship between structural and functional connectivity in the brain is a key question in connectomics. Here we quantify patterns of structure-function coupling across the neocortex, by comparing structural connectivity estimated using diffusion MRI with functional connectivity estimated using both neurophysiological (MEG-based) and haemodynamic (fMRI-based) recordings. We find that structure-function coupling is heterogeneous across brain regions and frequency bands. The link between structural and functional connectivity is generally stronger in multiple MEG frequency bands compared to resting state fMRI. Structure-function coupling is greater in slower and intermediate frequency bands compared to faster frequency bands. We also find that structure-function coupling systematically follows the archetypal sensorimotor-association hierarchy, as well as patterns of laminar differentiation, peaking in granular layer IV. Finally, structure-function coupling is better explained using structure-informed inter-regional communication metrics than using structural connectivity alone. Collectively, these results place neurophysiological and haemodynamic structure-function relationships in a common frame of reference and provide a starting point for a multi-modal understanding of structure-function coupling in the brain.

neuroscience↗

bioRxiv2022

Neuromaps: structural and functional interpretation of brain maps

Imaging technologies are increasingly used to generate high-resolution reference maps of brain structure and function. Modern scientific discovery relies on making comparisons between new maps (e.g. task activations, group structural differences) and these reference maps. Although recent data sharing initiatives have increased the accessibility of such brain maps, data are often shared in disparate coordinate systems (or "spaces"), precluding systematic and accurate comparisons among them. Here we introduce the neuromaps toolbox, an open-access software package for accessing, transforming, and analyzing structural and functional brain annotations. We implement two registration frameworks to generate high-quality transformations between four standard coordinate systems commonly used in neuroimaging research. The initial release of the toolbox features >40 curated reference maps and biological ontologies of the human brain, including maps of gene expression, neurotransmitter receptors, metabolism, neurophysiological oscillations, developmental and evolutionary expansion, functional hierarchy, individual functional variability, and cognitive specialization. Robust quantitative assessment of map-to-map similarity is enabled via a suite of spatial autocorrelation-preserving null models. By combining open-access data with transparent functionality for standardizing and comparing brain maps, the neuromaps software package provides a systematic workflow for comprehensive structural and functional annotation enrichment analysis of the human brain.

neuroscience↗

bioRxiv2021

Benchmarking functional connectivity by the structure and geometry of the human brain

The brains structural connectivity supports the propagation of electrical impulses, manifesting as patterns of co-activation, termed functional connectivity. Functional connectivity emerges from the underlying sparse structural connections, particularly through poly-synaptic communication. As a result, functional connections between brain regions without direct structural links are numerous, but their organization is not completely understood. Here we investigate the organization of functional connections without direct structural links. We develop a simple, data-driven method to benchmark functional connections with respect to their underlying structural and geometric embedding. We then use this method to re-weigh and re-express functional connectivity. We find evidence of unexpectedly strong functional connectivity within the canonical intrinsic networks of the brain. We also find unexpectedly strong functional connectivity at the apex of the unimodal-transmodal hierarchy. Our results suggest that both phenomena - functional modules and functional hierarchies - emerge from functional interactions that transcend the underlying structure and geometry. These findings also potentially explain recent reports that structural and functional connectivity gradually diverge in transmodal cortex. Collectively, we show how structural connectivity and geometry can be used as a natural frame of reference with which to study functional connectivity patterns in the brain.

neuroscience↗

bioRxiv2021

Time-resolved structure-function coupling in brain networks

The relationship between structural and functional connectivity in the brain is a key question in systems neuroscience. Modern accounts assume a single global structure-function relationship that persists over time. Here we show that structure-function coupling is dynamic and regionally heterogeneous. We use a temporal unwrapping procedure to identify moment-to-moment co-fluctuations in neural activity, and reconstruct time-resolved structure-function coupling patterns. We find that patterns of dynamic structure-function coupling are highly organized across the cortex. These patterns reflect cortical hierarchies, with stable coupling in unimodal and transmodal cortex, and dynamic coupling in intermediate regions, particularly in insular cortex (salience network) and frontal eye fields (dorsal attention network). Finally, we show that the variability of structure-function coupling is shaped by the distribution of connection lengths. The time-varying coupling of structural and functional connectivity points towards an informative feature of the brain that may reflect how cognitive functions are flexibly deployed and implemented.

neuroscience↗

bioRxiv2020

Sodium valproate protects against neuronal ferroptosis in epilepsy via suppressing lysyl oxidase

Background and purposeEpilepsy is a chronic neurological disease that is characterized by repetitive seizures. Seizures-related complications such as cognitive deficits, anxiety and sleep disorders seriously impact the life quality of patients. Antiepileptic drugs are widely used for the treatment of epilepsy. Sodium valproate is served as the first-line antiepileptic drugs and possesses various pharmacological effects on the brain. Sodium valproate exerts neuroprotective effects in acute nervous system diseases such as ischemic brain damage by inhibiting oxidative stress. However, the mechanism of neuroprotection of sodium valproate in epilepsy is unclear. Lysyl oxidase (Lox) is a monoamine oxidase that acts on extracellular matrix collagen and elastin and it can promote accumulation of oxidative stress. Our previous studies have confirmed that Lox is involved in ferroptosis, a novel iron-dependent and lipid peroxidation-mediated cell death pathway, during epilepsy. In this study, we would like to investigate whether sodium valproate can exert neuroprotective effects on kainic acid-induced epileptic seizures by inhibiting Lox-mediated ferroptosis. MethodsEpileptic mouse models were established by intracranial injection of 250 ng/l kainic acid on right hippocampus. Sodium valproate and ferroptosis inhibitors were administrated by intraperitoneal injecting. The epileptic behavior of the mice within 4 hours was recorded after intracranial injection of kainic acid. Mouse hippocampus was acquired to analyze the mRNA expression of prostaglandin-endoperoxide synthase 2 (PTGS2) and the production of 4-hydroxynonenal (4-HNE). In vitro, the protective effects of sodium valproate on glutamate-induced HT22 cell damage model was assessed by PI/Hoechst staining; The levels of PTGS2, 4-HNE and lipid ROS were analyzed by RT-qPCR, western blot and flow cytometry, respectively. RT-qPCR and Western blot analysis the mRNA and protein expression of Lox in the glutamate-induced HT22 cell damage model. The Lox overexpression model was established by intracranial injection of AAV on right hippocampus. ResultsPretreatment with sodium valproate and ferroptosis inhibitors could significantly alleviate the epileptic seizures in the kainic acid induced epilepsy mouse model. Western blot and RT-qPCR results showed that sodium valproate and ferroptosis inhibitors significantly inhibited the levels of 4-HNE and PTGS2. PI/Hoechst staining showed that 1 mM sodium valproate exerted protective effect on glutamate-induced HT22 cell injury model. There was no significant difference observed between sodium valproate and ferroptosis inhibitors co-intervention group and sodium valproate intervention group on glutamate-induced cell injury model. And sodium valproate could significantly inhibit the production of lipid reactive oxygen species and 4-HNE. The expression of Lox was significantly increased in the glutamate-induced HT22 cell injury model, which could be reversed by pretreatment of sodium valproate. And {beta}-aminopropionitrile (a specific inhibitor of Lox) could inhibit ferroptosis induced by glutamate, as well as ameliorate the epileptic seizures in the kainic acid induced epilepsy mouse model. Pretreatment with sodium valproate could not ameliorate the epileptic behavior in the Lox-overexpression mice. Western blot analysis showed that sodium valproate could not suppress the production of 4-HNE in kainic acid induced epileptic mice model. ConclusionsThe neuroprotective effect of sodium valproate in epileptic seizures is closely related to the inhibition of ferroptosis. The inhibition of ferroptosis is involved in the neuroprotective effect of sodium valproate on glutamate-induced HT22 cell damage model. Sodium valproate may exert neuroprotective effects in kainic acid-induced epileptic seizures by abrogating Lox-mediated ferroptosis.

neuroscience↗

bioRxiv2020

Agewise mapping of genomic oxidative DNA modification demonstrates oxidative-driven reprogramming of pro-longevity genes

The accumulation of unrepaired oxidatively damaged DNA can influence both the rate of ageing and life expectancy of an organism. Mapping oxidative DNA damage sites at whole-genome scale will help us to recognize the damage-prone sequence and genomic feature information, which is fundamental for ageing research. Here, we developed an algorithm to map the whole-genome oxidative DNA damage at single-base resolution using Single-Molecule Real-Time (SMRT) sequencing technology. We sequenced the genomic oxidative DNA damage landscape of C. elegans at different age periods to decipher the potential impact of genomic DNA oxidation on physiological ageing. We observed an age-specific pattern of oxidative modification in terms of motifs, chromosomal distribution, and genomic features. Integrating with RNA-Seq data, we demonstrated that oxidative modification in promoter regions was negatively associated with the expression of pro-longevity genes, denoting that oxidative modification in pro-longevity genes may exert epigenetic potential and thus affect lifespan determination. Together, our study opens up a new field for exploration of "oxigenetics," that focuses on the mechanisms of redox-mediated ageing. SummaryO_LIWe developed an algorithm to map the oxidative DNA damage at single-base resolution. C_LIO_LIOxidative DNA damage landscape in C. elegans illustrated an age-specific pattern in terms of motifs, chromosomal distribution, and genomic features. C_LIO_LIOxidative modification in older worms occurred higher frequency at the sex chromosome, with the preference for promoter and exon regions. C_LIO_LIOxidative modification in promoter regions of pro-longevity genes was negatively associated with their expression, suggesting the oxidative-driven transcript reprogramming of pro-longevity genes in physiological ageing. C_LI

genetics↗

bioRxiv2020

Signal propagation via cortical hierarchies

The wiring of the brain is organized around a putative unimodal-transmodal hierarchy. Here we investigate how this intrinsic hierarchical organization of the brain shapes the transmission of information among regions. The hierarchical positioning of individual regions was quantified by applying diffusion map embedding to resting state functional MRI networks. Structural networks were reconstructed from diffusion spectrum imaging and topological shortest paths among all brain regions were computed. Sequences of nodes encountered along a path were labelled by their hierarchical position, tracing out path motifs. We find that the cortical hierarchy guides communication in the network. Specifically, nodes are more likely to forward signals to nodes closer in the hierarchy and cover a range of unimodal and transmodal regions, potentially enriching or diversifying signals en route. We also find evidence of systematic detours, particularly in attention networks, where communication is re-routed. Altogether, the present work highlights how the cortical hierarchy shapes signal exchange and imparts behaviourally-relevant communication patterns in brain networks.

neuroscience↗

bioRxiv2019

Lysyl oxidase promotes neuronal ferroptosis exacerbating seizure-induced hippocampal damage

Epilepsy is a serious neurological disorder and characterized by recurrent and unprovoked seizures. A critical pathological factor in the seizure genesis is neuronal loss. However, mechanisms which lead to neuronal death remain elusive. Our present investigation depicted that ferroptosis, a recently discovered iron- and lipid peroxidation-dependent cell death, probably served as a mechanism in murine models of kainic acid (KA)-induced seizures. And treatment with ferroptosis inhibitors ferrostatin-1 (Fer-1), liproxstatin-1 (Lipo-1) or deferoxamine (DFO) significantly suppressed seizure severity and frequency. Using gene expression profiling in HT22 cells after glutamate exposure (a validated ferroptotic cell death model), we identified lysyl oxidase (Lox) as a novel inducer of ferroptosis. Mechanistically, Lox promoted ferroptosis via activation of extracellular regulated protein kinase (ERK)-dependent 5-lipoxygenase (Alox5) phosphorylation at serine 663 residue signaling, subsequent leading to lipid reactive oxygen species (ROS) accumulation. In a murine model of KA-induced seizure, we illustrated that administration of {beta}-aminopropionitrile (BAPN), a specific Lox inhibitor, remarkably prevented seizure generation. Overall, these findings highlight Lox, a novel identified ferroptotic regulator in neurons, serves as a potential target for seizure-related disease including epilepsy.

neuroscience↗