Heterocephalus Research Articles

Multi-Controller Placement Optimization Using Naked Mole-Rat Algorithm over Software-Defined Networking Environment

Software Defined Networking (SDN) is the novel networking paradigm where decoupling of the control plane from the data plane has its inherent advantages. Controller Placement Problem (CPP) involves placing the optimal number of controllers at the appropriate locations while meeting prerequisites such as latency, load balancing, energy and computational time. To achieve scalability, deployment of multiple controllers on large-scale SDN is one of the key challenges. CPP can be addressed as a multi-objective combinatorial optimization problem whose solution is a trade-off between multiple optimization parameters. In this paper, a novel population-based meta-heuristic algorithm viz. Naked Mole-Rat (NMR) Algorithm has been proposed to optimize the location for controller placement based on Switch-Controller (SC), Controller-Controller (CC) latency while maintaining load balancing among the controllers. The ideas and mechanisms are illustrated using two publicly available standard topologies viz. Ernet and Savvis. The controller localization approach implemented with NMR algorithm has slightly a better result as compared with the Bat algorithm.

Comparison of degu (Octodon degus), Naked Mole Rat, Mouse and Human genomes identified common hallmarks of aging and Alzheimer's Disease

AbstractBackgroundTo provide new insight into the mechanisms of Alzheimer’s disease (AD) pathogenesis and aid the discovery of new therapies in humans it is important to expand and complement research using mouse models by developing, characterizing, and validating suitable new or unconventional mammalian, non‐murine models of AD. Our goal was to create genome assemblies at the chromosome level associated with AD‐like pathogenesis using two long‐lived animal models. The degu (Octodon degus) which naturally exhibits AD neuropathology and the naked mole rat (H. glaber) best known for its resistance to cancer and aging. To understand evolutionary paths to longevity and associated diseases like AD we characterized their genome features and identified common substitutions in long‐lived rodents that support enhanced tolerance to DNA damage.MethodSynteny maps among M. musculus, H. glaber, H. sapiens and O. degus were created using SyMAP 5.0.6. To evaluate disease‐related mutations in humans a pairwise comparison of protein sequences was performed using the HGMD.ResultWe identified several synteny blocks that were part of the putative rodent ancestor genome. 78% genome was covered in H. glaber and 75% coverage in O. degus. In addition, 58 of the 426 synteny blocks were longer than 10 Mbp in M. musculus and 62 in O. degus. The identification of substitutions in orthologs at disease‐causing sites revealed that DNA damage and repair genes are under selection in long‐lived species. Our comparative genomic analyses identified that the top disease categories enriched in degu and naked mole rat were associated with lipid metabolism, DNA repair, stress and IGF‐1.ConclusionOur comparative genome analysis revealed changes in genes and pathways associated with adaptations to acquired longevity. Substitutions at AD causing sites may contribute to long‐term survival pathways affected by natural selection in long‐lived models. When compared to short‐lived mouse models, pathways associated with lipid metabolism, oxidative stress and DNA repair were identified. This data is particularly valuable for providing a within family (Rodentia) comparison for mouse AD model genomics to develop a comprehensive analysis to determine conserved genetic alterations between the unconventional animal models and to bridge our existing databases of mouse models and humans.

Mechanisms of Aging from a Genetic, Molecular and Lifestyle Perspective.

Aging is an evitable part of the lives of every organism. However, many organisms are capable of bending the rules and experience an increased longevity. Among these are turtles, elephants, whales and most importantly – humans. Definition for the discussion of anti-aging and longevity is presented alongside a historic analysis of the reasons for this venture. An examination of the adaptations of both short-lived, such as the mayfly, and long-lived organisms like turtles, the naked mole rat Heterocephalus glaber and the American lobster Homarus americanus for their possible human applications. Several studies on the genetics and molecular basis of longevity are presented and debated upon. Finally, there is an examination of possible cultural lifestyle effects on longevity, such as one’s environmental stresses, diet and nutrition, and physical activity. Overall, showing that a combination of genetic, molecular and lifestyle factors strongly affect and allow one to surpass the typical life expectancy.

Unusual occurrence of domestication syndrome amongst African mole-rats: Is the naked mole-rat a domestic animal?

The Naked mole-rat (NMR) is becoming a prominent model organism due to its peculiar traits, such as eusociality, extreme longevity, cancer resistance, and reduced pain sensitivity. It belongs to the African mole-rats (AMR), a family of subterranean rodents that includes solitary, cooperative breeding and eusocial species. We identified and quantified the domestication syndrome (DS) across AMR, a set of morphological and behavioural traits significantly more common and pronounced amongst domesticated animals than in their wild counterparts. Surprisingly, the NMR shows apparent DS traits when compared to the solitary AMR. Animals can self-domesticate when a reduction of the fear response is naturally selected, such as in islands with no predators, or to improve the group’s harmony in cooperative breeding species. The DS may be caused by alterations in the physiology of the neural crest cells (NCC), a transient population of cells that generate a full range of tissues during development. The NCC contribute to organs responsible for transmitting the fear response and various other tissues, including craniofacial bones. Therefore, mutations affecting the NCC can manifest as behavioural and morphological alterations in many structures across the body, as seen in neurocristopathies. We observed that all social AMRs are chisel-tooth diggers, an adaption to hard soils that requires the flattening of the skull. We hypothesise that chisel-tooth digging could impose a selective pressure on the NCC that triggered the DS’s appearance, possibly facilitating the evolution of sociality. Finally, we discuss how DS traits are neutral or beneficial for the subterranean niche, strategies to test this hypothesis and report well-studied mutations in the NMR that are associated with the NCC physiology or with the control of the fear response. In conclusion, we argue that many of the NMR’s unconventional traits are compatible with the DS and provide a hypothesis about its origins. Our model proposes a novel avenue to enhance the understanding of the extraordinary biology of the NMR.

The longest-lived metazoan, Arctica islandica, exhibits high mitochondrial H2O2 removal capacities

A greater capacity of endogenous matrix antioxidants has recently been hypothesized to characterize mitochondria of long-lived species, curbing bursts of reactive oxygen species (ROS) generated in this organelle. Evidence for this has been obtained from studies comparing the long-lived naked mole rat to laboratory mice. We tested this hypothesis by comparing the longest-lived metazoan, the marine bivalve Arctica islandica (MLSP = 507 y), with shorter-lived and evolutionarily related species. We used a recently developed fluorescent technique to assess mantle and gill tissue mitochondria’s capacity to consume hydrogen peroxide (H2O2) in multiple physiological states ex vivo. Depending on the type of respiratory substrate provided, mitochondria of Arctica islandica could consume between 3 and 14 times more H2O2 than shorter-lived species. These findings support the contention that a greater capacity for the elimination of ROS characterizes long-lived species, a novel property of mitochondria thus far demonstrated in two key biogerontological models from distant evolutionary lineages.

Short communication: Acute hypoxia does not alter mitochondrial abundance in naked mole-rats

Hypoxia poses a significant energetic challenge and most species exhibit metabolic remodelling when exposed to prolonged hypoxia. One component of this remodelling is mitochondrial biogenesis/mitophagy, which alter mitochondrial abundance and helps to adjust metabolic throughput to match changes in energy demands in hypoxia. However, how acute hypoxia impacts mitochondrial abundance in hypoxia-tolerant species is poorly understood. To help address this gap, we exposed hypoxia-tolerant naked mole-rats to 3 h of normoxia or acute hypoxia (5% O2) and measured changes in mitochondrial abundance using two well-established markers: citrate synthase (CS) enzyme activity and mitochondrial DNA (mtDNA) abundance. We found that neither marker changed with hypoxia in brain, liver, or kidney, suggesting that mitochondrial biogenesis is not initiated during acute hypoxia in these tissues. Conversely in skeletal muscle, the ratio of CS activity to total protein decreased 50% with hypoxia. However, this change was likely driven by an increase in soluble protein density in hypoxia because CS activity was unchanged relative to wet tissue weight and the mtDNA copy number was unchanged. To confirm this, we examined skeletal muscle mitochondria using transmission electron microscopy and found no change in mitochondrial volume density. Taken together with previous studies of mitochondrial respiratory function, our present findings suggest that naked mole-rats primarily rely on tissue-specific functional remodelling of metabolic pathways and mitochondrial respiratory throughput, and not physical changes in mitochondrial number or volume, to adjust to short-term hypoxic exposure.

Aggression, Boldness, and Exploration Personality Traits in the Subterranean Naked Mole-Rat (Heterocephalus glaber) Disperser Morphs.

Animal personality traits (consistent behavioral differences between individuals in their behavior across time and/or situation) affect individual fitness through facets, such as dispersal. In eusocial naked mole-rat (Heterocephalus glaber) colonies, a disperser morph may arise with distinct morphological, behavioral, and physiological characteristics. This study aimed to quantify the personality traits of a cohort of disperser morphs of naked mole-rat (NMR). Behavioral tests were performed on twelve disperser morphs (six males and six females) in an observation tunnel system that was novel and unfamiliar. Novel stimuli (fresh snakeskin, tissue paper, and conspecific of the same sex) were introduced for fifteen minutes, and the behavioral acts of the individual were recorded. A total of 30 behaviors were noted during the behavioral tests of which eight were used to quantify aggression, boldness, and exploration. The NMR disperser morphs showed consistent individual differences in boldness, and exploration across time and test, indicating a distinct personality. In addition, new naked mole-rat responses including disturbance behaviors; confront, barricade, and stay-away, were recorded. Further investigations into the relationships between animal personality traits and social hierarchy position in entire colonies are needed for more informative results as we further investigate the role of personality in cooperatively breeding societies.

Complementary evolution of coding and noncoding sequence underlies mammalian hairlessness.

Body hair is a defining mammalian characteristic, but several mammals, such as whales, naked mole-rats, and humans, have notably less hair. To find the genetic basis of reduced hair quantity, we used our evolutionary-rates-based method, RERconverge, to identify coding and noncoding sequences that evolve at significantly different rates in so-called hairless mammals compared to hairy mammals. Using RERconverge, we performed a genome-wide scan over 62 mammal species using 19,149 genes and 343,598 conserved noncoding regions. In addition to detecting known and potential novel hair-related genes, we also discovered hundreds of putative hair-related regulatory elements. Computational investigation revealed that genes and their associated noncoding regions show different evolutionary patterns and influence different aspects of hair growth and development. Many genes under accelerated evolution are associated with the structure of the hair shaft itself, while evolutionary rate shifts in noncoding regions also included the dermal papilla and matrix regions of the hair follicle that contribute to hair growth and cycling. Genes that were top ranked for coding sequence acceleration included known hair and skin genes KRT2, KRT35, PKP1, and PTPRM that surprisingly showed no signals of evolutionary rate shifts in nearby noncoding regions. Conversely, accelerated noncoding regions are most strongly enriched near regulatory hair-related genes and microRNAs, such as mir205, ELF3, and FOXC1, that themselves do not show rate shifts in their protein-coding sequences. Such dichotomy highlights the interplay between the evolution of protein sequence and regulatory sequence to contribute to the emergence of a convergent phenotype.

Socially Induced Infertility in Naked and Damaraland Mole-Rats: A Tale of Two Mechanisms of Social Suppression.

The naked mole-rat (Heterocephalus glaber) and the Damaraland mole-rat (Fukomys damarensis) possess extreme reproductive skew with a single reproductive female responsible for reproduction. In this review, we synthesize advances made into African mole-rat reproductive patterns and physiology within the context of the social control of reproduction. Non-reproductive female colony members have low concentrations of luteinising hormone (LH) and a reduced response of the pituitary to a challenge with gonadotropin releasing hormone (GnRH). If the reproductive female is removed from the colony, an increase in the basal plasma LH and increased pituitary response to a GnRH challenge arises in the non-reproductive females, suggesting the reproductive female controls reproduction. Non-reproductive male Damaraland mole-rats have basal LH concentrations and elevated LH concentrations in response to a GnRH challenge comparable to the breeding male, but in non-breeding male naked mole-rats, the basal LH concentrations are low and there is a muted response to a GnRH challenge. This renders these two species ideal models to investigate physiological, behavioural and neuroendocrine mechanisms regulating the hypothalamic-pituitary-gonadal axis. The recently discovered neuropeptides kisspeptin and RFamide-related peptide-3 are likely candidates to play an important role in the regulation of reproductive functions in the two mole-rat species.

The Naked Mole-Rat as a Model for Healthy Aging.

Naked mole-rats (NMRs, Heterocephalus glaber) are the longest-lived rodents with a maximum life span exceeding 37 years. They exhibit a delayed aging phenotype and resistance to age-related functional decline/diseases. Specifically, they do not display increased mortality with age, maintain several physiological functions until nearly the end of their lifetime, and rarely develop cancer and Alzheimer's disease. NMRs live in a hypoxic environment in underground colonies in East Africa and are highly tolerant of hypoxia. These unique characteristics of NMRs have attracted considerable interest from zoological and biomedical researchers. This review summarizes previous studies of the ecology, hypoxia tolerance, longevity/delayed aging, and cancer resistance of NMRs and discusses possible mechanisms contributing to their healthy aging. In addition, we discuss current issues and future perspectives to fully elucidate the mechanisms underlying delayed aging and resistance to age-related diseases in NMRs.

Structural consequences of sequence variation in mammalian prion β2α2 loop segments.

Sequence variation in the β2α2 loop, residues 165-175 of the mammalian prion protein (PrP), influences its structure. To better understand the consequences of sequence variation in this region of the protein, we biochemically and biophysically interrogate natural and artificial sequence variants of the β2α2 loop of mammalian PrP. Using microcrystal electron diffraction (MicroED), we determine atomic resolution structures of segments encompassing residues 168-176 from the β2α2 loop of PrP with sequences corresponding to human, mouse/cow, bank vole/hamster, rabbit/pig/guinea pig, and naked mole rat (elk-T174S) β2α2 loops, as well as synthetic β2α2 loop sequences. This collection of structures presents two dominant amyloid packing polymorphisms. In the first polymorph, denoted "clasped", side chains within a sheet form polar clasps by facing each other on the same strand, exemplified by the mouse/cow, human, and bank vole/hamster sequences. Because its stability is derived from within a strand and through polar ladders within a sheet, the sequence requirements for the mating strand are less restrictive. A second polymorph, denoted "interdigitated," has sidechains interdigitate across mating sheets, exemplified by the elk, naked mole rat (elk T174S), and rabbit sequences. The two types of packing present distinct networks of stabilizing hydrogen bonds. The identity of residue 174 appears to strongly influence the packing adopted in these peptides, but consideration of the overall sequence of a given segment is needed to understand the stability of its assemblies. Incorporation of these β2α2 loop sequences into an 85 residue recombinant segment encoding wild-type bank vole PrP94-178 demonstrates that even single residue substitutions could impact fibril morphology as evaluated by negative stain electron microscopy. This is in line with recent findings supporting the accessibility of different structural geometries by varied mammalian prion sequences, and indicates that sequence-specific polymorphisms may be influenced by residues in the β2α2 loop.

Functional anatomy and disparity of the postcranial skeleton of African mole-rats (Bathyergidae)

The burrowing adaptations of the appendicular system of African mole-rats (Bathyergidae) have been comparatively less investigated than their cranial adaptations. Because bathyergids exhibit different digging modes (scratch-digging and chisel-tooth digging) and social systems (from solitary to highly social), they are a unique group to assess the effects of distinct biomechanical regimes and social organization on morphology. We investigated the morphological diversity and intraspecific variation of the appendicular system of a large dataset of mole-rats (n = 244) including seven species and all six bathyergid genera. Seventeen morpho-functional indices from stylopodial (femur, humerus) and zeugopodial (ulna, tibia-fibula) elements were analyzed with multivariate analysis. We hypothesized that scratch-diggers (i.e., Bathyergus) would exhibit a more specialized skeletal phenotype favoring powerful forelimb digging as compared to the chisel-tooth diggers, and that among chisel-tooth diggers, the social taxa will exhibit decreased limb bone specializations as compared to solitary taxa due to colony members sharing the costs of digging. Our results show that most bathyergids have highly specialized fossorial traits, although such specializations were not more developed in Bathyergus (or solitary species), as predicted. Most chisel tooth-diggers are equally, or more specialized than scratch-diggers. Heterocephalus glaber contrasted significantly from other bathyergids, presenting a surprisingly less specialized fossorial morphology. Our data suggests that despite our expectations, chisel-tooth diggers have a suite of appendicular adaptations that have allowed them to maximize different aspects of burrowing, including shoulder and neck support for forward force production, transport and removal of soils out of the burrow, and bidirectional locomotion. It is probably that both postcranial and cranial adaptations in bathyergids have played an important role in the successful colonization of a wide range of habitats and soil conditions within their present distribution.

A hybrid transient search naked mole-rat optimizer for image segmentation using multilevel thresholding

This paper introduces a new hybrid algorithm named Transient Search Naked Mole-Rat Optimizer (TsNMRO), based on the hybridization of transient search optimizer (TSO) merged in the naked mole-rat algorithm (NMRA). To improve the worker phase of traditional NMRA, the new algorithm combines TSO’s exploratory notions with NMRA. A novel stagnation phase motivated by the grey wolf optimizer (GWO) and cuckoo search (CS) algorithms has been implemented to tackle the local optima stagnation problem. In addition, self-adaptivity has been included by adjusting all of the proposed algorithm’s parameters. For varied parameters of the algorithm under examination, a simulated annealing (sa) based mutation technique has been used, requiring no user-based parametric modifications. CEC 2005, CEC 2019 benchmark challenges, and image thresholding issues are identified to evaluate the TsNMRO’s performance. The significance of the suggested technique across higher dimensional problems and variable function evaluations has been demonstrated by a comparison of varying dimension sizes. It can be observed from the experimental outcomes that the suggested TsNMRO outperforms competitive methods in terms of mean and standard deviation values for most of the cases. The suggested TsNMRO’s improved performance is further validated by statistical results such as Freidman’s test, Wilcoxon’s rank-sum test and convergence profiles.

Not just a cousin of the naked mole-rat: Damaraland mole-rats offer unique insights into biomedicine.

Evolutionary medicine has been a fast-growing field of biological research in the past decade. One of the strengths of evolutionary medicine is to use non-traditional model organisms which often exhibit unusual characteristics shaped by natural selection. Studying these unusual traits could provide valuable insight to understand biomedical questions, since natural selection likely discovers solutions to those complex biological problems. Because of many unusual traits, the naked mole-rat (NMR) has attracted attention from different research areas such as aging, cancer, and hypoxia- and hypercapnia-related disorders. However, such uniqueness of NMR physiology may sometimes make the translational study to human research difficult. Damaraland mole-rat (DMR) shares multiple characteristics in common with NMR, but shows higher degree of similarity with human in some aspects of their physiology. Research on DMR could therefore offer alternative insights and might bridge the gap between experimental findings from NMR to human biomedical research. In this review, we discuss studies of DMR as an extension of the current set of model organisms to help better understand different aspects of human biology and disease. We hope to encourage researchers to consider studying DMR together with NMR. By studying these two similar but evolutionarily distinct species, we can harvest the power of convergent evolution and avoid the potential biased conclusions based on life-history of a single species.

Social stress is unlikely to play a major role in reproductive suppression of female subordinate naked mole-rats and Damaraland mole-rats.

Social stress is unlikely to play a major role in reproductive suppression of female subordinate naked mole-rats and Damaraland mole-rats.

Small RNA sequencing in hypoxic naked mole-rat hearts suggests microRNA regulation of RNA- and translation-related processes.

The naked mole-rat (Heterocephalus glaber) regularly endures intermittent periods of hypoxia in its burrows, surviving in part due to metabolic rate depression (MRD)-a strategy of conserving cellular resources by downregulating nonessential gene expression and reorganizing cellular processes. miRNA are short, noncoding RNAs already implicated for their roles in numerous models of extreme environmental stress; given their rapid, reversible nature, they are ideal for implementing MRD. We performed small RNA sequencing on cardiac tissue from normoxic versus 24 h hypoxic naked mole-rats, and used bioinformatics to predict 18 miRNAs which may be differentially regulated during hypoxia. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway mapping further suggest these miRNAs play roles in largely translation-related functions, including RNA processing and catabolism.

Carcinogenesis resistance in the longest-lived rodent, the naked mole-rat.

Certain mammalian species are resistant to cancer, and a better understanding of how this cancer resistance arises could provide valuable insights for basic cancer research. Recent technological innovations in molecular biology have allowed the study of cancer-resistant mammals, despite the fact that they are not the classical model animals, which are easily studied using genetic approaches. Naked mole-rats (NMRs; Heterocephalus glaber) are the longest-lived rodent, with a maximum lifespan of more than 37 years, and almost never show spontaneous carcinogenesis. NMRs are currently attracting much attention from aging and cancer researchers, and published studies on NMR have continued to increase over the past decade. Cancer development occurs via multiple steps and involves many biological processes. Recent research on the NMR as a model for cancer resistance suggests that they possess various unique carcinogenesis-resistance mechanisms, including efficient DNA repair pathways, cell-autonomous resistance to transformation, and dampened inflammatory response. Here, we summarize the molecular mechanisms of carcinogenesis resistance in NMR, which have been uncovered over the past two decades, and discuss future perspectives.

Protracted neuronal maturation in a long-lived, highly social rodent.

Naked mole-rats are a long-lived rodent species (current lifespan >37 years) and an increasingly popular biomedical model. Naked mole-rats exhibit neuroplasticity across their long lifespan. Previous studies have begun to investigate their neurogenic patterns. Here, we test the hypothesis that neuronal maturation is extended in this long-lived rodent. We characterize cell proliferation and neuronal maturation in established rodent neurogenic regions over 12 months following seven days of consecutive BrdU injection. Given that naked mole-rats are eusocial (high reproductive skew where only a few socially-dominant individuals reproduce), we also looked at proliferation in brain regions relevant to the social-decision making network. Finally, we measured co-expression of EdU (newly-born cells), DCX (immature neuron marker), and NeuN (mature neuron marker) to assess the timeline of neuronal maturation in adult naked mole-rats. This work reaffirms the subventricular zone as the main source of adult cell proliferation and suggests conservation of the rostral migratory stream in this species. Our profiling of socially-relevant brain regions suggests that future work which manipulates environmental context can unveil how newly-born cells integrate into circuitry and facilitate adult neuroplasticity. We also find naked mole-rat neuronal maturation sits at the intersection of rodents and long-lived, non-rodent species: while neurons can mature by 3 weeks (rodent-like), most neurons mature at 5 months and hippocampal neurogenic levels are low (like long-lived species). These data establish a timeline for future investigations of longevity- and socially-related manipulations of naked mole-rat adult neurogenesis.

The effect of chaotic mapping on naked mole-rat algorithm for energy efficient smart city wireless sensor network

Naked mole-rat algorithm (NMRA) is a recently introduced swarm intelligent algorithm based on the matting pattern of naked mole-rats. Though the algorithm is competitive but still shows poor exploration properties and slow convergence. In the present work, chaos theory has been introduced to enhance the exploration properties of NMRA. Apart from that, parametric adaptation has been added to analyse the effect of mating factor (λ) using various chaotic maps (such as chebyshev map, circle map, iterative map etc.) on NMRA. Based on these chaotic maps, ten variants of NMRA are proposed, and their performance is evaluated for CEC 2005 test suite subjected to different population and dimension sets. Further, the best variant among the proposed variants is evaluated for CEC 2014 benchmark functions, 100-digit challenge problems (CEC 2019) and three engineering design problems. In addition, to check the effectiveness of proposed best variant, it is further applied to real time problem of energy efficient and prolonged lifetime design of wireless sensor network for smart city framework. The results of best proposed variant are compared with other state-of-the-art algorithms namely differential evolution with adaptive properties (JADE), whale optimization algorithm with opposition and exponential properties (OEWOA), sine cosine crow search algorithm (SCCSA), self-adaptive differential evolution (SaDE), success-history based differential evolution along with parameter adaption (SHADE), equilibrium optimizer (EO), flower pollination algorithm based on fractional order calculus (FA-FPO), Gaussian-salp swarm algorithm (GSSA), variable neighbourhood bat algorithm (VNBA), blended biogeography-based optimization (B-BBO), improved elephant herding optimization (IMEHO), original NMRA and others. Experimental results validate the performance of the proposed NMRA with Chebyshev map (CNMRA) as the best well supported by Wilcoxon rank-sum test and Friedman rank (f-rank) test, concerning other algorithms used for comparison.

Caveolin-1 suppresses hippocampal neuron apoptosis via the regulation of HIF1α in hypoxia in naked mole-rats.

Naked mole-rats (NMRs) (Heterocephalus glaber) are highly social and subterranean rodents with large communal colonies in burrows containing low oxygen levels. The inhibition of severe hypoxic conditions is of particular interest to this study. To understand the mechanisms that facilitate neuronal preservation during hypoxia, we investigated the proteins regulating hypoxia tolerance in NMR hippocampal neurons. Caveolin-1 (Cav-1), a transmembrane scaffolding protein, confers prosurvival signalling in the central nervous system. The present study aimed to investigate the role of Cav-1 in hypoxia-induced neuronal injury. Western blotting analysis and immunocytochemistry showed that Cav-1 expression was significantly upregulated in NMR hippocampal neurons under 8% O2 conditions for 8 h. Cav-1 alleviates apoptotic neuronal death from hypoxia. Downregulation of Cav-1 by lentiviral vectors suggested damage to NMR hippocampal neurons under hypoxic conditions in vitro and in vivo. Overexpression of Cav-1 by LV-Cav-1 enhanced hypoxic tolerance of NMR hippocampal neurons in vitro and in vivo. Mechanistically, the levels of hypoxia inducible factor-1α (HIF-1α) are also increased under hypoxic conditions. After inhibiting the binding of HIF-1α to hypoxia response elements in the DNA by echinomycin, Cav-1 levels were downregulated significantly. Furthermore, chromatin immunoprecipitation assays showed the direct role of HIF1α in regulating the expression levels of Cav-1 in NMR hippocampal neurons under hypoxic conditions. These findings suggest that Cav-1 plays a critical role in modulating the apoptosis of NMR hippocampal neurons and warrant further studies targeting Cav-1 to treat hypoxia-associated brain diseases.