Gene Expression Plasticity Research Articles

HIV-1 subtypes B and C Tat differentially impact synaptic plasticity expression and implicates HIV-associated neurocognitive disorders.

Earlier studies have established that infection with HIV-1 subtypes (clades) might differentially influence the neuropathogenesis of HIV-1-associated neurocognitive dysfunction (HAND). HIV-1 Trans activator of transcription protein (Tat) is of considerable significance and plays a major role in the central nervous system (CNS) dysfunction. However, these HIV-1 clades exert diverse cellular effects that leads to neuropathogenic dysfunction has not been well established. We hypothesized that the HIV-1 clade B and clade C Tat proteins effect synaptic plasticity expression in neuroblastoma cells (SK-N-MC) by diverse methods, and accordingly modulates the development of HAND. In the present study, we have analyzed important and highly expressed 84 key human synaptic plasticity genes expression which differentially impact in clade B and clade C Tat treated SK-N-MC cells using RT(2) Profile PCR Array human Synaptic Plasticity kit. Observed results demonstrate that out of 84 key synaptic plasticity genes, 36 and 25 synaptic genes were substantially (≥3 fold) up-regulated and 5 and 5 genes considerably (≥3 fold) down-regulated in clade B and clade C Tat treated cells, respectively, compared to the control SK-N-MC. We have also estimated the levels of glutamine and glutamate in HIV-1 clade B and C Tat exposed SK-N-MC cells compared to untreated cells. Our results indicate that levels of glutamate, glutamine and expression of synaptic plasticity genes were highly dysregulated by HIV-1 clade B Tat compared to clade C Tat in SK-N-MC cells. In summary, this study suggests that clade B Tat substantially potentiates neuronal toxicity and further dysregulated synaptic plasticity genes in SK-N-MC may contribute to the severe neuropathogenesis linked with HAND.

Parasitism and survival rate of Diadegma fenestrale (Hymenoptera: Ichneumonidae) and DfIV gene expression patterns in two lepidopteran hosts

The genus Diadegma is a well-known parasitoid group and some are known to have symbiotic virus, polydnavirus (PDV). A novel IV was discovered from the calyx of Diadegma fenestrale female and sequenced its genome. D. fenestrale has more than two hosts, including potato tuber moth (PTM) and diamondback moth (DBM). D. fenestrale preferred PTM to DBM as hosts based on the oviposition and survival rate. Nevertheless, the developmental period and morphology of D. fenestrale were not significantly different between PTM and DBM. We compared DfIV gene expression patterns between PTM and DBM under various conditions to understand the phenomena. DfIV genes were more widely expressed in PTM with large numbers than in DBM after parasitized by D. fenestrale, particularly at the initial point. They showed differential expression patterns between two lepidopteran hosts. This DfIV gene expression plasticity showed a dependency on the lepidopteran host species and parasitization time, suggesting that it may contribute to increase the parasitoid survival rate. This might be one of the key elements that determine the symbiotic relationship between PDV and parasitoid.

Plasticity of chemoreceptor gene expression: Sensory and circuit inputs modulate state-dependent chemoreceptors.

Animals dramatically modify their chemosensory behaviors when starved, which could allow them to alter and optimize their food-search strategies. Dynamic changes in the gene expression of chemoreceptors may be a general mechanism underlying food and state-dependent changes in chemosensory behaviors. In our recent study,1 we identified chemoreceptors in the ADL sensory neuron type of C. elegans that are modulated by feeding state and food availability. Here, we highllight our recent findings by which sensory inputs into ADL, neuronal outputs from ADL, and circuit inputs from the RMG interneuron, which is electrically connected to ADL, are required to regulate an ADL-expressed chemoreceptor. This sensory and circuit-mediated regulation of chemoreceptor gene expression is dependent on cell-autonomous pathways acting in ADL, e.g. KIN-29, DAF-2, OCR-2 and calcium signaling, and circuit inputs from RMG mediated by NPR-1. Based on these findings, we propose an intriguing but speculative feedback modulatory circuit mechanism by which sensory perception of food and internal state signals may be coupled to regulate ADL-expressed chemoreceptors, which may allow animals to precisely regulate and fine-tune their chemosensory neuron responses as a function of feeding state.

Differential Regulation of Gene Expression of Alveolar Epithelial Cell Markers in Human Lung Adenocarcinoma-Derived A549 Clones.

Stem cell therapy appears to be promising for restoring damaged or irreparable lung tissue. However, establishing a simple and reproducible protocol for preparing lung progenitor populations is difficult because the molecular basis for alveolar epithelial cell differentiation is not fully understood. We investigated an in vitro system to analyze the regulatory mechanisms of alveolus-specific gene expression using a human alveolar epithelial type II (ATII) cell line, A549. After cloning A549 subpopulations, each clone was classified into five groups according to cell morphology and marker gene expression. Two clones (B7 and H12) were further analyzed. Under serum-free culture conditions, surfactant protein C (SPC), an ATII marker, was upregulated in both H12 and B7. Aquaporin 5 (AQP5), an ATI marker, was upregulated in H12 and significantly induced in B7. When the RAS/MAPK pathway was inhibited, SPC and thyroid transcription factor-1 (TTF-1) expression levels were enhanced. After treatment with dexamethasone (DEX), 8-bromoadenosine 3′5′-cyclic monophosphate (8-Br-cAMP), 3-isobutyl-1-methylxanthine (IBMX), and keratinocyte growth factor (KGF), surfactant protein B and TTF-1 expression levels were enhanced. We found that A549-derived clones have plasticity in gene expression of alveolar epithelial differentiation markers and could be useful in studying ATII maintenance and differentiation.

Plumage color and pathogen-induced gene expression in a wild bird

Ornamentation is hypothesized to signal the capacity of an individual to cope with environmental challenges. At the molecular level, organisms respond to their environments largely by altering gene transcription, but the transcriptional responses linking ornamentation and disease resistance are virtually unstudied. In the house finch (Haemorhous mexicanus), carotenoid coloration displayed by males is important in female choice, and plumage redness predicts a male’s ability to recover from bacterial infection with Mycoplasma gallisepticum. To investigate the molecular mechanisms underlying links between ornamentation and disease response, we experimentally infected wild finches and used microarrays to identify genes that were differentially expressed in males with redder and yellower plumage coloration. Sixteen candidate genes were then investigated across individuals. Principal components analysis revealed that infection induced a marginally significant decrease in 11 genes, several with primary immune functions. The treatment by plumage color interaction effect was largely driven by greater disease-induced changes in expression of heat shock protein 90 and ubiquitin c (the second principal component) by red birds than by yellow birds. In a direct comparison of disease severity between infected birds, plumage color on its own did not significantly predict disease symptoms. However, in multivariate models, expression of genes loading on the second principal component, plumage color, and their interaction were significant predictors of the severity of disease symptoms. Our observations demonstrate links between ornamentation and expression of genes related to disease resistance; we suggest that male plumage color may reflect functionally associated differences in inducibility or plasticity of gene expression in this species.

Regulation of gene expression and pain states by epigenetic mechanisms.

The induction of inflammatory or neuropathic pain states is known to involve molecular activity in the spinal superficial dorsal horn and dorsal root ganglia, including intracellular signaling events which lead to changes in gene expression. These changes ultimately cause alterations in macromolecular synthesis, synaptic transmission, and structural architecture which support central sensitization, a process required for the establishment of long-term pain states. Epigenetic mechanisms are essential for long-term synaptic plasticity and modulation of gene expression. This is because epigenetic modifications are known to regulate gene transcription by aiding the physical relaxation or condensation of chromatin. These processes are therefore potential regulators of the molecular changes underlying permanent pain states. A handful of studies have emerged in the field of pain epigenetics; however, the field is still very much in its infancy. This chapter draws upon other specialities which have extensively investigated epigenetic mechanisms, such as learning and memory and oncology. After defining epigenetics as well as the recent field of "neuroepigenetics" and the main molecular mechanisms involved, this chapter describes the role of these mechanisms in the synaptic plasticity seen in learning and memory, and address those epigenetic mechanisms that have been linked with the development of acute and prolonged pain states. Finally, the idea that long-lasting epigenetic modifications could contribute to the transition from acute to chronic pain states by supporting maladaptive molecular changes is discussed.

Bimodal signatures of germline methylation are linked with gene expression plasticity in the coral Acropora millepora.

BackgroundIn invertebrates, genes belonging to dynamically regulated functional categories appear to be less methylated than “housekeeping” genes, suggesting that DNA methylation may modulate gene expression plasticity. To date, however, experimental evidence to support this hypothesis across different natural habitats has been lacking.ResultsGene expression profiles were generated from 30 pairs of genetically identical fragments of coral Acropora millepora reciprocally transplanted between distinct natural habitats for 3 months. Gene expression was analyzed in the context of normalized CpG content, a well-established signature of historical germline DNA methylation. Genes with weak methylation signatures were more likely to demonstrate differential expression based on both transplant environment and population of origin than genes with strong methylation signatures. Moreover, the magnitude of expression differences due to environment and population were greater for genes with weak methylation signatures.ConclusionsOur results support a connection between differential germline methylation and gene expression flexibility across environments and populations. Studies of phylogenetically basal invertebrates such as corals will further elucidate the fundamental functional aspects of gene body methylation in Metazoa.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-1109) contains supplementary material, which is available to authorized users.

Self administration of oxycodone alters synaptic plasticity gene expression in the hippocampus differentially in male adolescent and adult mice

Abuse and addiction to prescription opioids such as oxycodone (a short-acting Mu opioid receptor (MOP-r) agonist) in adolescence is a pressing public health issue. We have previously shown differences in oxycodone self-administration behaviors between adolescent and adult C57BL/6J mice and expression of striatal neurotransmitter receptor genes, in areas involved in reward. In this study, we aimed to determine whether oxycodone self-administration differentially affects genes regulating synaptic plasticity in the hippocampus of adolescent compared to adult mice, since the hippocampus may be involved in learning aspects associated with chronic drug self administration. Hippocampus was isolated for mRNA analysis from mice that had self administered oxycodone (0.25mg/kg/infusion) 2h/day for 14 consecutive days or from yoked saline controls. Gene expression was analyzed with real-time polymerase chain reaction (PCR) using a commercially available “synaptic plasticity” PCR array containing 84 genes. We found that adolescent and adult control mice significantly differed in the expression of several genes in the absence of oxycodone exposure, including those coding for mitogen-activated protein kinase, calcium/calmodulin-dependent protein kinase II gamma subunit, glutamate receptor, ionotropic AMPA2 and metabotropic 5. Chronic oxycodone self administration increased proviral integration site 1 (Pim1) and thymoma viral proto-oncogene 1 mRNA levels compared to controls in both age groups. Both Pim1 and cadherin 2 mRNAs showed a significant combined effect of Drug Condition and Age×Drug Condition. Furthermore, the mRNA levels of both cadherin 2 and cAMP response element modulators showed an experiment-wise significant difference between oxycodone and saline control in adult but not in adolescent mice. Overall, this study demonstrates for the first time that chronic oxycodone self-administration differentially alters synaptic plasticity gene expression in the hippocampus of adolescent and adult mice.

Prenatal Choline Supplementation Ameliorates the Long-Term Neurobehavioral Effects of Fetal-Neonatal Iron Deficiency in Rats

Background:Gestational iron deficiency in humans and rodents produces long-term deficits in cognitive and socioemotional function and alters expression of plasticity genes in the hippocampus that persist despite iron treatment. Prenatal choline supplementation improves cognitive function in other rodent models of developmental insults. Objective:The objective of this study was to determine whether prenatal choline supplementation prevents the long-term effects of fetal-neonatal iron deficiency on cognitive and social behaviors and hippocampal gene expression. Methods:Pregnant rat dams were administered an iron-deficient (2–6 g/kg iron) or iron-sufficient (IS) (200 g/kg iron) diet from embryonic day (E) 3 to postnatal day (P) 7 with or without choline supplementation (5 g/kg choline chloride, E11–18). Novel object recognition (NOR) in the test vs. acquisition phase, social approach (SA), and hippocampal mRNA expression were compared at P65 in 4 male adult offspring groups: formerly iron deficient (FID), FID with choline supplementation (FID-C), IS, and IS with choline supplementation. Results:Relative to the intact NOR in IS rats (acquisition: 47.9%, test: 60.2%, P < 0.005), FID adult rats had impaired recognition memory at the 6-h delay (acquisition: 51.4%, test: 55.1%, NS), accompanied by a 15% reduction in hippocampal expression of brain-derived neurotrophic factor (Bdnf) (P< 0.05) and myelin basic protein (Mbp) (P < 0.05). Prenatal choline supplementation in FID rats restored NOR (acquisition: 48.8%, test: 64.4%, P < 0.0005) and increased hippocampal gene expression (FID-C vs. FID group: Bdnf, Mbp,P < 0.01). SA was also reduced in FID rats (P < 0.05 vs. IS rats) but was only marginally improved by prenatal choline supplementation. Conclusions:Deficits in recognition memory, but not social behavior, resulting from gestational iron deficiency are attenuated by prenatal choline supplementation, potentially through preservation of hippocampal Bdnf and Mbp expression. Prenatal choline supplementation may be a promising adjunct treatment for fetal-neonatal iron deficiency.

Phenotypic plasticity of HSP70s gene expression during diapause: signs of evolutionary responses to cold stress among Soybean Pod Borer populations (Leguminivora glycinivorella) in Northeast of China.

The soybean pod borer (Leguminivora glycinivorella Matsumura) successfully survives the winter because of its high expression of 70-kDa heat shock proteins (HSP70s) during its overwintering diapause. The amount of HSP70s is different under different environmental stresses. In this study, inducible heat shock protein 70 and its constitutive heat shock cognate 70 were cloned by RT-PCR and RACE. These genes were named Lg-hsp70 and Lg-hsc70, respectively. Gene transcription and protein expression after cold stress treatment (5°C to −5°C) were analyzed by western blotting and by qRT-PCR for four populations that were sampled in the northeast region of China, including Shenyang, Gongzhuling, Harbin and Heihe, when the soybean pod borer was in diapause. As the cold shock temperature decreased, the levels of Lg-HSP70s were significantly up-regulated. The amount of cold-induced Lg-HSP70s was highest in the southernmost population (Shenyang, 41°50′N) and lowest in the northernmost population (Heihe, 50°22′N). These results support the hypothesis that the soybean pod borer in the northeast region of China displays phenotypic plasticity, and the accumulation of Lg-HSP70s is a strategy for overcoming environmental stress. These results also suggest that the induction of HSP70 synthesis, which is a complex physiological adaptation, can evolve quickly and inherit stability.

Gene expression plasticity resulting from parental leaf damage in Mimulus guttatus.

Leaf trichome density in Mimulus guttatus can be altered by the parental environment. In this study, we compared global gene expression patterns in progeny of damaged and control plants. Significant differences in gene expression probably explain the observed trichome response, and identify additional responsive pathways. Using whole transcriptome RNA sequencing, we estimated differential gene expression between isogenic seedlings whose parents had, or had not, been subject to leaf damage. We identified over 900 genes that were differentially expressed in response to parental wounding. These genes clustered into groups involved in cell wall and cell membrane development, stress response pathways, and secondary metabolism. Gene expression is modified as a consequence of the parental environment in a targeted way that probably alters multiple developmental pathways, and may increase progeny fitness if they experience environments similar to that of their parents.

Nonsyntenic genes drive highly dynamic complementation of gene expression in maize hybrids.

Maize (Zea mays) displays an exceptional level of structural genomic diversity, which is likely unique among higher eukaryotes. In this study, we surveyed how the genetic divergence of two maize inbred lines affects the transcriptomic landscape in four different primary root tissues of their F1-hybrid progeny. An extreme instance of complementation was frequently observed: genes that were expressed in only one parent but in both reciprocal hybrids. This single-parent expression (SPE) pattern was detected for 2341 genes with up to 1287 SPE patterns per tissue. As a consequence, the number of active genes in hybrids exceeded that of their parents in each tissue by >400. SPE patterns are highly dynamic, as illustrated by their excessive degree of tissue specificity (80%). The biological significance of this type of complementation is underpinned by the observation that a disproportionally high number of SPE genes (75 to 82%) is nonsyntenic, as opposed to all expressed genes (36%). These genes likely evolved after the last whole-genome duplication and are therefore younger than the syntenic genes. In summary, SPE genes shape the remarkable gene expression plasticity between root tissues and complementation in maize hybrids, resulting in a tissue-specific increase of active genes in F1-hybrids compared with their inbred parents.

Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons.

L-lactate is a product of aerobic glycolysis that can be used by neurons as an energy substrate. Here we report that in neurons L-lactate stimulates the expression of synaptic plasticity-related genes such as Arc, c-Fos, and Zif268 through a mechanism involving NMDA receptor activity and its downstream signaling cascade Erk1/2. L-lactate potentiates NMDA receptor-mediated currents and the ensuing increase in intracellular calcium. In parallel to this, L-lactate increases intracellular levels of NADH, thereby modulating the redox state of neurons. NADH mimics all of the effects of L-lactate on NMDA signaling, pointing to NADH increase as a primary mediator of L-lactate effects. The induction of plasticity genes is observed both in mouse primary neurons in culture and in vivo in the mouse sensory-motor cortex. These results provide insights for the understanding of the molecular mechanisms underlying the critical role of astrocyte-derived L-lactate in long-term memory and long-term potentiation in vivo. This set of data reveals a previously unidentified action of L-lactate as a signaling molecule for neuronal plasticity.

Acoustic trauma triggers upregulation of serotonin receptor genes

Hearing loss induces plasticity in excitatory and inhibitory neurotransmitter systems in auditory brain regions. Excitatory-inhibitory balance is also influenced by a range of neuromodulatory regulatory systems, but less is known about the effects of auditory damage on these networks. In this work, we studied the effects of acoustic trauma on neuromodulatory plasticity in the auditory midbrain of CBA/J mice. Quantitative PCR was used to measure the expression of serotonergic and GABAergic receptor genes in the inferior colliculus (IC) of mice that were unmanipulated, sham controls with no hearing loss, and experimental individuals with hearing loss induced by exposure to a 116 dB, 10 kHz pure tone for 3 h. Acoustic trauma induced substantial hearing loss that was accompanied by selective upregulation of two serotonin receptor genes in the IC. The Htr1B receptor gene was upregulated tenfold following trauma relative to shams, while the Htr1A gene was upregulated threefold. In contrast, no plasticity in serotonin receptor gene expression was found in the hippocampus, a region also innervated by serotonergic projections. Analyses in the IC demonstrated that acoustic trauma also changed the coexpression of genes in relation to each other, leading to an overexpression of Htr1B compared to other genes. These data suggest that acoustic trauma induces serotonergic plasticity in the auditory system, and that this plasticity may involve comodulation of functionally-linked receptor genes.

Gene expression plasticity evolves in response to colonization of freshwater lakes in threespine stickleback.

Phenotypic plasticity is predicted to facilitate individual survival and/or evolve in response to novel environments. Plasticity that facilitates survival should both permit colonization and act as a buffer against further evolution, with contemporary and derived forms predicted to be similarly plastic for a suite of traits. On the other hand, given the importance of plasticity in maintaining internal homeostasis, derived populations that encounter greater environmental heterogeneity should evolve greater plasticity. We tested the evolutionary significance of phenotypic plasticity in coastal British Columbian postglacial populations of threespine stickleback (Gasterosteus aculeatus) that evolved under greater seasonal extremes in temperature after invading freshwater lakes from the sea. Two ancestral (contemporary marine) and two derived (contemporary freshwater) populations of stickleback were raised near their thermal tolerance extremes, 7 and 22 °C. Gene expression plasticity was estimated for more than 14,000 genes. Over five thousand genes were similarly plastic in marine and freshwater stickleback, but freshwater populations exhibited significantly more genes with plastic expression than marine populations. Furthermore, several of the loci shown to exhibit gene expression plasticity have been previously implicated in the adaptive evolution of freshwater populations, including a gene involved in mitochondrial regulation (PPARAa). Collectively, these data provide molecular evidence that highlights the importance of plasticity in colonization and adaptation to new environments.

Vorinostat positively regulates synaptic plasticity genes expression and spine density in HIV infected neurons: role of nicotine in progression of HIV-associated neurocognitive disorder.

BackgroundHIV-associated neurocognitive disorder (HAND) is characterized by development of cognitive, behavioral and motor abnormalities, and occurs in approximately 50% of HIV infected individuals. In the United States, the prevalence of cigarette smoking ranges from 35-70% in HIV-infected individuals compared to 20% in general population. Cognitive impairment in heavy cigarette smokers has been well reported. However, the synergistic effects of nicotine and HIV infection and the underlying mechanisms in the development of HAND are unknown.ResultsIn this study, we explored the role of nicotine in the progression of HAND using SK-N-MC, a neuronal cell line. SK-N-MC cells were infected with HIV-1 in the presence or absence of nicotine for 7 days. We observed significant increase in HIV infectivity in SK-N-MC treated with nicotine compared to untreated HIV-infected neuronal cells. HIV and nicotine synergize to significantly dysregulate the expression of synaptic plasticity genes and spine density; with a concomitant increase of HDAC2 levels in SK-N-MC cells. In addition, inhibition of HDAC2 up-regulation with the use of vorinostat resulted in HIV latency breakdown and recovery of synaptic plasticity genes expression and spine density in nicotine/HIV alone and in co-treated SK-N-MC cells. Furthermore, increased eIF2 alpha phosphorylation, which negatively regulates eukaryotic translational process, was observed in HIV alone and in co-treatment with nicotine compared to untreated control and nicotine alone treated SK-N-MC cells.ConclusionsThese results suggest that nicotine and HIV synergize to negatively regulate the synaptic plasticity gene expression and spine density and this may contribute to the increased risk of HAND in HIV infected smokers. Apart from disrupting latency, vorinostat may be a useful therapeutic to inhibit the negative regulatory effects on synaptic plasticity in HIV infected nicotine abusers.

Developmental hypothyroidism reduces the expression of activity-dependent plasticity genes in dentate gyrus of the adult following long-term potentiation

Developmental hypothyroidism reduces the expression of activity-dependent plasticity genes in dentate gyrus of the adult following long-term potentiation

Conservation and divergence of gene expression plasticity following c. 140 million years of evolution in lodgepole pine (Pinus contorta) and interior spruce (Picea glauca×Picea engelmannii).

Species respond to environmental stress through a combination of genetic adaptation and phenotypic plasticity, both of which may be important for survival in the face of climatic change. By characterizing the molecular basis of plastic responses and comparing patterns among species, it is possible to identify how such traits evolve. Here, we used de novo transcriptome assembly and RNAseq to explore how patterns of gene expression differ in response to temperature, moisture, and light regime treatments in lodgepole pine (Pinus contorta) and interior spruce (a natural hybrid population of Picea glauca and Picea engelmannii). We found wide evidence for an effect of treatment on expression within each species, with 6413 and 11,658 differentially expressed genes identified in spruce and pine, respectively. Comparing patterns of expression among these species, we found that 74% of all orthologs with differential expression had a pattern that was conserved in both species, despite 140 million yr of evolution. We also found that the specific treatments driving expression patterns differed between genes with conserved versus diverged patterns of expression. We conclude that natural selection has probably played a role in shaping plastic responses to environment in these species.

Commentary: ADHD and social disadvantage: an inconvenient truth? – a reflection on Russell et al. () and Larsson et al. ()

In the 1950's, many experts believed hyperkinesis was a neurotic reaction to inner conflicts arising from early family experiences. In the 1990's, many experts believed ADHD to be 'genetic' (without a mechanistic explanation of what that meant). Both views appear naïve today in a scientific world grappling with the complexity of highly plastic gene expression, gene x environment interplay, and epigenetic, context-dependent emergence of psychopathology. Both views also fail to account for the uncomfortable fact that ADHD is also associated with social disadvantage - a level of analysis required in a developmental psychopathology approach. That developmental psychopathology approach, pioneered a generation ago, initially emphasized the accumulation of risk and protective factors, and emerged in a contemporary systemic approach that seeks to determine whether it is risk accumulation (e.g., allostatic load) or specific risk factors (e.g., family process) that mechanistically shape psychopathology. Despite the prominence of the developmental psychopathology perspective, the social context of ADHD is surprisingly neglected today. Both Russell etal. (this issue, 2014) and Larsson etal. (this issue, 2014) take strides toward remedying this state of affairs.

Parent-of-origin genetic background affects the transcriptional levels of circadian and neuronal plasticity genes following sleep loss

Sleep homoeostasis refers to a process in which the propensity to sleep increases as wakefulness progresses and decreases as sleep progresses. Sleep is tightly organized around the circadian clock and is regulated by genetic and epigenetic mechanisms. The homoeostatic response of sleep, which is classically triggered by sleep deprivation, is generally measured as a rebound effect of electrophysiological measures, for example delta sleep. However, more recently, gene expression changes following sleep loss have been investigated as biomarkers of sleep homoeostasis. The genetic background of an individual may affect this sleep-dependent gene expression phenotype. In this study, we investigated whether parental genetic background differentially modulates the expression of genes following sleep loss. We tested the progeny of reciprocal crosses of AKR/J and DBA/2J mouse strains and we show a parent-of-origin effect on the expression of circadian, sleep and neuronal plasticity genes following sleep deprivation. Thus, we further explored, by in silico, specific functions or upstream mechanisms of regulation and we observed that several upstream mechanisms involving signalling pathways (i.e. DICER1, PKA), growth factors (CSF3 and BDNF) and transcriptional regulators (EGR2 and ELK4) may be differentially modulated by parental effects. This is the first report showing that a behavioural manipulation (e.g. sleep deprivation) in adult animals triggers specific gene expression responses according to parent-of-origin genomic mechanisms. Our study suggests that the same mechanism may be extended to other behavioural domains and that the investigation of gene expression following experimental manipulations should take seriously into account parent-of-origin effects.