Showing papers on "Developmental plasticity published in 2009"
TL;DR: Recent evidence for structural forms of synaptic plasticity in the mammalian cortex involves cell type-specific structural plasticity: some boutons and dendritic spines appear and disappear, accompanied by synapse formation and elimination, respectively.
Abstract: Synaptic plasticity in adult neural circuits may involve the strengthening or weakening of existing synapses as well as structural plasticity, including synapse formation and elimination. Indeed, long-term in vivo imaging studies are beginning to reveal the structural dynamics of neocortical neurons in the normal and injured adult brain. Although the overall cell-specific morphology of axons and dendrites, as well as of a subpopulation of small synaptic structures, are remarkably stable, there is increasing evidence that experience-dependent plasticity of specific circuits in the somatosensory and visual cortex involves cell type-specific structural plasticity: some boutons and dendritic spines appear and disappear, accompanied by synapse formation and elimination, respectively. This Review focuses on recent evidence for such structural forms of synaptic plasticity in the mammalian cortex and outlines open questions.
1,696 citations
TL;DR: Mice deficient for STAT4 and T-bet-two prototypical Th1 transcription factors are protected from autoimmunity associated with Th17 pathogenesis and support a model of late Th17 developmental plasticity with implications for autoIMmunity and host defense.
1,033 citations
TL;DR: The subtle adjustments needed to ensure developmental plasticity in IUGR are provided by epigenetic modulation of critical genes, accompanied by changes in the quantity and activity of enzymes responsible for making modifications to chromatin as well as global and gene-specific modifications of chromatin.
Abstract: Purpose of review—Intrauterine growth restriction (IUGR) is associated with an increased propensity to develop adult onset disease and is described by the developmental origins of adult disease hypothesis. Sequelae of fetal growth restriction include metabolic disease as well as nonmetabolic disorders. Although it has become clear that the morbidities associated with IUGR are complex and result from disruptions to multiple pathways and multiple organs, the mechanisms driving the long-term effects are only just beginning to be understood. Recent findings—IUGR affects most organ systems by either interrupting developmental processes such as apoptosis or producing lasting changes to levels of key regulatory factors. Both of these are associated with an often persistent change in gene expression. Epigenetic modulation of transcription is a mechanism that is at least partially responsible for this. IUGR is accompanied by changes in the quantity and activity of enzymes responsible for making modifications to chromatin as well as global and gene-specific modifications of chromatin. Summary—The subtle adjustments needed to ensure developmental plasticity in IUGR are provided by epigenetic modulation of critical genes. Translating the messages of the epigenetic profile and identifying the players that mediate the effects remains one of the major challenges in the field. An understanding of the mechanisms driving the epigenetic changes will facilitate identification of dietary and pharmaceutical approaches that can be applied in the postnatal period.
813 citations
TL;DR: It is proposed that synaptic mechanisms underlying sensory cortical plasticity map onto specific functional components of plasticity, which occur in common across the primary somatosensory, visual, and auditory cortices.
Abstract: Sensory experience and learning alter sensory representations in cerebral cortex. The synaptic mechanisms underlying sensory cortical plasticity have long been sought. Recent work indicates that long-term cortical plasticity is a complex, multicomponent process involving multiple synaptic and cellular mechanisms. Sensory use, disuse, and training drive long-term potentiation and depression (LTP and LTD), homeostatic synaptic plasticity and plasticity of intrinsic excitability, and structural changes including formation, removal, and morphological remodeling of cortical synapses and dendritic spines. Both excitatory and inhibitory circuits are strongly regulated by experience. This review summarizes these findings and proposes that these mechanisms map onto specific functional components of plasticity, which occur in common across the primary somatosensory, visual, and auditory cortices.
647 citations
TL;DR: The evidence that environmental influences during mammalian development lead to stable changes in the epigenome that alter the individual's susceptibility to chronic metabolic and cardiovascular disease is reviewed, and the clinical implications are discussed.
Abstract: Cellular commitment to a specific lineage is controlled by differential silencing of genes, which in turn depends on epigenetic processes such as DNA methylation and histone modification. During early embryogenesis, the mammalian genome is 'wiped clean' of most epigenetic modifications, which are progressively re-established during embryonic development. Thus, the epigenome of each mature cellular lineage carries the record of its developmental history. The subsequent trajectory and pattern of development are also responsive to environmental influences, and such plasticity is likely to have an epigenetic basis. epigenetic marks may be transmitted across generations, either directly by persisting through meiosis or indirectly through replication in the next generation of the conditions in which the epigenetic change occurred. Developmental plasticity evolved to match an organism to its environment, and a mismatch between the phenotypic outcome of adaptive plasticity and the current environment increases the risk of metabolic and cardiovascular disease. These considerations point to epigenetic processes as a key mechanism that underpins the developmental origins of chronic noncommunicable disease. Here, we review the evidence that environmental influences during mammalian development lead to stable changes in the epigenome that alter the individual's susceptibility to chronic metabolic and cardiovascular disease, and discuss the clinical implications.
574 citations
TL;DR: Brain plasticity provides a basis for developing better therapies to improve outcome from acquired brain injuries and TMS and other forms of brain stimulation are also being used experimentally to enhance brain plasticity and recovery of function.
Abstract: Neuronal plasticity allows the central nervous system to learn skills and remember information, to reorganize neuronal networks in response to environmental stimulation, and to recover from brain and spinal cord injuries. Neuronal plasticity is enhanced in the developing brain and it is usually adaptive and beneficial but can also be maladaptive and responsible for neurological disorders in some situations. Basic mechanisms that are involved in plasticity include neurogenesis, programmed cell death, and activity-dependent synaptic plasticity. Repetitive stimulation of synapses can cause long-term potentiation or long-term depression of neurotransmission. These changes are associated with physical changes in dendritic spines and neuronal circuits. Overproduction of synapses during postnatal development in children contributes to enhanced plasticity by providing an excess of synapses that are pruned during early adolescence. Clinical examples of adaptive neuronal plasticity include reorganization of cortical maps of the fingers in response to practice playing a stringed instrument and constraint-induced movement therapy to improve hemiparesis caused by stroke or cerebral palsy. These forms of plasticity are associated with structural and functional changes in the brain that can be detected with magnetic resonance imaging, positron emission tomography, or transcranial magnetic stimulation (TMS). TMS and other forms of brain stimulation are also being used experimentally to enhance brain plasticity and recovery of function. Plasticity is also influenced by genetic factors such as mutations in brain-derived neuronal growth factor. Understanding brain plasticity provides a basis for developing better therapies to improve outcome from acquired brain injuries.
442 citations
TL;DR: It is now apparent that there is substantial plasticity late in the Th17 program, which allows committed Th17 cells to transition from effectors that produce predominantly IL-17A andIL-17F, to effectors That produce predominantly IFNgamma, and raises new questions regarding the stability of epigenetic modifications that accompany induction of cytokine gene expression during T cell lineage development.
402 citations
University of Auckland1, University of Southampton2, University of Cambridge3, University College London4, Aga Khan University5, Russian Academy6, French Institute of Health and Medical Research7, Centre for Cellular and Molecular Biology8, University of Bristol9, Harvard University10, University of the West Indies11, Swarthmore College12, Tel Aviv University13, University of New Mexico14, University of London15, University of Sydney16, University of Chile17, Smithsonian Tropical Research Institute18
TL;DR: Developmental plasticity has been viewed traditionally in the context of major disruptions such as caused by teratogens, prematurity and growth retardation, but there is increasing appreciation of the role of developmental plasticity.
389 citations
TL;DR: Recent progress in understanding the mechanisms that restrict the action of BDNF to active synapses and by which BDNF mediates chemical and structural modifications of individual synapses are discussed, placing an emphasis on the role of local protein synthesis in these processes.
318 citations
TL;DR: This work compares spontaneous and experience-dependent structural plasticity with lesion-induced (reactive) structural Plasticity that occurs during development and in the adult brain.
308 citations
TL;DR: Understanding mechanisms at the interface between environmental stimuli and innate genetic programs leading to the sculpting of neuronal circuits during early brain development may give insight into the formation of critical periods of developmental plasticity.
TL;DR: The identification of "plasticity genes" regulated by changes in the levels of electrical activity are reviewed, and how elucidating their cellular functions has revealed the intimate role transcriptional regulation plays in fundamental aspects of synaptic transmission and circuit plasticity that occur in the brain on an every day basis.
Abstract: The mammalian brain is plastic in the sense that it shows a remarkable capacity for change throughout life. The contribution of neuronal activity to brain plasticity was first recognized in relation to critical periods of development, when manipulating the sensory environment was found to profoundly affect neuronal morphology and receptive field properties. Since then, a growing body of evidence has established that brain plasticity extends beyond development and is an inherent feature of adult brain function, spanning multiple domains, from learning and memory to adaptability of primary sensory maps. Here we discuss evolution of the current view that plasticity of the adult brain derives from dynamic tuning of transcriptional control mechanisms at the neuronal level, in response to external and internal stimuli. We then review the identification of “plasticity genes” regulated by changes in the levels of electrical activity, and how elucidating their cellular functions has revealed the intimate role transcriptional regulation plays in fundamental aspects of synaptic transmission and circuit plasticity that occur in the brain on an every day basis.
TL;DR: In this review, the neurobiological characteristics of zinc will be discussed, including its distribution and the processes by which its homeostasis is regulated, and the substantial effects zinc may have on neuronal functioning will be examined.
TL;DR: This paper outlines some important milestones in the history of the term “plasticity” in reference to the nervous system and shows how an analysis in depth can clarify some confusion engendered by an unrestricted use of the concept and term of neural plasticity.
Abstract: In this paper, we outline some important milestones in the history of the term “plasticity” in reference to the nervous system. Credit is given to William James for first adopting the term to denote changes in nervous paths associated with the establishment of habits; to Eugenio Tanzi for first identifying the articulations between neurons, not yet called synapses, as possible sites of neural plasticity; to Ernesto Lugaro for first linking neural plasticity with synaptic plasticity; and to Cajal for complementing Tanzi’s hypothesis with his own hypothesis of plasticity as the result of the formation of new connections between cortical neurons. Cajal’s early use of the word plasticity is demonstrated, and his subsequent avoidance of the term is tentatively accounted for by the fact that other authors extended it to mean neuronal reactions partly pathological and no doubt quite different from those putatively associated with normal learning. Evidence is furnished that in the first two decades of the twentieth century the theory was generally accepted that learning is based on a reduced resistance at exercized synapses, and that neural processes become associated by coactivation. Subsequently the theory fell in disgrace when Lashley’s ideas about mass action and functional equipotentiality of the cortex tended to outmode models of the brain based on orthodox neural circuitry. The synaptic plasticity theory of learning was rehabilitated in the late 1940s when Konorski and particularly Hebb argued successfully that there was no better alternative way to think about the modifiability of the brain by experience and practice. Hebb’s influential hypothesis about the mechanism of adult learning contained elements strikingly similar to the early speculations of James, Tanzi and Cajal, but Hebb did not acknowledge specifically these roots of his thinking about the brain, though he was fully aware that he had resurrected old ideas wrongly neglected for a long time. Lately the concept of neural plasticity has been complicated by attributing considerably different meanings to it. A scholarly paper by Paillard is used to show how an analysis in depth can clarify some confusion engendered by an unrestricted use of the concept and term of neural plasticity.
TL;DR: This review will summarize recent knowledge on hormonal networks that regulate the development and growth of root with focus on the hormonal interactions that shape the root apical meristem.
Abstract: Plants exhibit an amazing developmental flexibility. Plant embryogenesis results in the establishment of a simple apical-basal axis represented by apical shoot and basal root meristems. Later, during postembryonic growth, shaping of the plant body continues by the formation and activation of numerous adjacent meristems that give rise to lateral shoot branches, leaves, flowers, or lateral roots. This developmental plasticity reflects an important feature of the plant's life strategy based on the rapid reaction to different environmental stimuli, such as temperature fluctuations, availability of nutrients, light or water and response resulting in modulation of developmental programs. Plant hormones are important endogenous factors for the integration of these environmental inputs and regulation of plant development. After a period of studies focused primarily on single hormonal pathways that enabled us to understand the hormone perception and signal transduction mechanisms, it became obvious that the developmental output mediated by a single hormonal pathway is largely modified through a whole network of interactions with other hormonal pathways. In this review, we will summarize recent knowledge on hormonal networks that regulate the development and growth of root with focus on the hormonal interactions that shape the root apical meristem.
TL;DR: This work sitsuate multiple molecular mechanisms that underlie structural and functional plasticity in visual cortex in the context of a new conceptual framework of feed-forward and feedback regulation for understanding how neurons of the visual cortex reorganize their connections in response to changes in sensory inputs.
Abstract: A remarkable amount of our current knowledge of mechanisms underlying experience-dependent plasticity during cortical development comes from study of the mammalian visual cortex. Recent advances in high-resolution cellular imaging, combined with genetic manipulations in mice, novel fluorescent recombinant probes, and large-scale screens of gene expression, have revealed multiple molecular mechanisms that underlie structural and functional plasticity in visual cortex. We situate these mechanisms in the context of a new conceptual framework of feed-forward and feedback regulation for understanding how neurons of the visual cortex reorganize their connections in response to changes in sensory inputs. Such conceptual advances have important implications for understanding not only normal development but also pathological conditions that afflict the central nervous system.
TL;DR: Of particular interest is the question of how to link the molecular and cellular mechanisms of synaptic plasticity to learning operations at the systems level, which are expressed behaviourally as reinforcement-related learning.
TL;DR: It is found that loss of plasticity and differentiation onset depends on the Polycomb complex protein mes-2/E(Z), which orchestrates large-scale changes in chromatin organization and gene expression to promote the timely loss of developmental plasticity.
TL;DR: Changes in density of parvalbumin‐containing cells and perineuronal nets during development of mouse barrel cortex and after brief univibrissa and chessboard experience in adolescence are examined to suggest the involvement of both tested factors in closing the critical period in barrels in an experience‐dependent manner.
Abstract: The ability to undergo experience-dependent plasticity in the neocortex is often limited to early development, but also to particular cortical loci and specific experience. In layers II-IV of the barrel cortex, plasticity evoked by removing all but one vibrissae (univibrissa rearing) does not have a time limit except for layer IV barrels, where it can only be induced during the first postnatal week. In contrast, deprivation of every second vibrissa (chessboard deprivation) removes time limits for plasticity. The mechanism permitting plasticity in response to chessboard deprivation and halting it in reply to univibrissa rearing is unknown. Condensation of chondroitin sulfate proteoglycans into perineuronal nets and an increase in intracortical inhibition mediated by parvalbumin-containing interneurons are implicated in closing the critical period for ocular dominance plasticity. These factors could also be involved in setting up the critical period in barrels in a way that depends on a particular sensory experience. We therefore examined changes in density of parvalbumin-containing cells and perineuronal nets during development of mouse barrel cortex and after brief univibrissa and chessboard experience in adolescence. We observed a progressive increase in the density of the two markers across cortical layers between postnatal day 10 and 20, which was especially pronounced in the barrels. Univibrissa rearing, but not chessboard deprivation, increased the density of perineuronal nets and parvalbumin-containing cells in the deprived barrels, but only those that immediately neighbour the undeprived barrel. These data suggest the involvement of both tested factors in closing the critical period in barrels in an experience-dependent manner.
TL;DR: Understanding the underlying mechanisms behind the spontaneous expression of the crossed phrenic pathway either in the developing animal or after chronic spinal cord injury in the adult animal may provide clues to initiating respiratory recovery sooner to alleviate human suffering and eventually eliminate the leading cause of death in human cases of spinal Cord injury.
TL;DR: Underlying cellular and physiological mechanisms relevant to age-at-injury effects will be described in considerable detail, including but not limited to alterations in neurotransmission, connectivity/network functioning, the extracellular matrix, response to oxidative stress and changes in cerebral metabolism.
Abstract: Acquired brain injuries represent a major cause of disability in the pediatric population. Understanding responses to developmental acquired brain injuries requires knowledge of the neurobiology of normal development, age-at-injury effects and experience-dependent neuroplasticity. In the developing brain, full recovery cannot be considered as a return to the premorbid baseline, since ongoing maturation means that cerebral functioning in normal individuals will continue to advance. Thus, the recovering immature brain has to ‘hit a moving target’ to achieve full functional recovery, defined as parity with age-matched uninjured peers. This review will discuss the consequences of developmental injuries such as focal lesions, diffuse hypoxia and traumatic brain injury (TBI). Underlying cellular and physiological mechanisms relevant to age-at-injury effects will be described in considerable detail, including but not limited to alterations in neurotransmission, connectivity/network functioning, the extracellular matrix, response to oxidative stress and changes in cerebral metabolism. Finally, mechanisms of experience-dependent plasticity will be reviewed in conjunction with their effects on neural repair and recovery.
TL;DR: Heterosynaptic changes which take place according to predispositions for plasticity may provide a useful mechanism(s) for homeostasis of neurons’ synaptic weights and extending the lifetime of memory traces during ongoing learning in neuronal networks.
Abstract: Ongoing learning continuously shapes the distribution of neurons’ synaptic weights in a system with plastic synapses Plasticity may change the weights of synapses that were active during the induction—homosynaptic changes, but also may change synapses not active during the induction—heterosynaptic changes Here we will argue, that heterosynaptic and homosynaptic plasticity are complementary processes, and that heterosynaptic plasticity might accompany homosynaptic plasticity induced by typical pairing protocols Synapses are not uniform in their susceptibility for plastic changes, but have predispositions to undergo potentiation or depression, or not to change Predisposition is one of the factors determining the direction and magnitude of homo- and heterosynaptic changes Heterosynaptic changes which take place according to predispositions for plasticity may provide a useful mechanism(s) for homeostasis of neurons’ synaptic weights and extending the lifetime of memory traces during ongoing learning in neuronal networks
TL;DR: Results demonstrate that JH has condition-dependent effects and clarify how JH can mediate different behaviors in well nourished queens and poorly nourished workers, and suggest differential endocrine responses are likely to be a widespread mechanism mediating behavioral and physiological plasticity.
TL;DR: These findings implicate CB1-dependent plasticity in systems-level development and early postnatal plasticity of the whisker map and suggest that plasticity effects were not secondary to gross activity changes.
TL;DR: It is argued that it is important to consider environmentally induced phenotypic variation resulting directly from both natural‐ and human‐induced ecological change as a source of the distinctive morphologies of domesticated plants.
Abstract: The fields of human behavioral ecology (HBE) and evolutionary developmental biology (evo-devo) both stand to make significant contributions to our understanding of agricultural origins. These two approaches share a concern with phenotypic plasticity and its evolutionary significance. HBE considers the adaptive plasticity of the human phenotype in response to resource distribution in time and space and has helped to advance understanding of the economic costs and benefits of food production. However, evo-devo and the associated subject of phenotypic (developmental) plasticity have so far been largely neglected as sources of insight into the domestication of plants, despite growing evidence for their evolutionary importance in nature and their roles in the origins of novel traits. We argue that it is important to consider environmentally induced phenotypic variation resulting directly from both natural- and human-induced ecological change as a source of the distinctive morphologies of domesticated plants.
TL;DR: BDNF–TrkB-dependent maturation of glutamatergic synapses is tightly associated with a loss of endogenous KAR activity, which suggests a critical role for BDNF TrkB signaling in fast activity-dependent regulation of KARs.
Abstract: Immature hippocampal synapses express presynaptic kainate receptors (KARs), which tonically inhibit glutamate release. Presynaptic maturation involves activity-dependent downregulation of the tonic KAR activity and consequent increase in release probability; however, the molecular mechanisms underlying this developmental process are unknown. Here, we have investigated whether brain derived neurotrophic factor (BDNF), a secreted protein implicated in developmental plasticity in several areas of the brain, controls presynaptic maturation by regulating KARs. Application of BDNF in neonate hippocampal slices resulted in increase in synaptic transmission that fully occluded the immature-type KAR activity in area CA1. Conversely, genetic ablation of BDNF was associated with delayed synaptic maturation and persistent presynaptic KAR activity, suggesting a role for endogenous BDNF in the developmental regulation of KAR function. In addition, our data suggests a critical role for BDNF TrkB signaling in fast activity-dependent regulation of KARs. Selective acute inhibition of TrkB receptors using a chemical-genetic approach prevented rapid change in synapse dynamics and loss of tonic KAR activity that is typically seen in response to induction of LTP at immature synapses. Together, these data show that BDNF-TrkB-dependent maturation of glutamatergic synapses is tightly associated with a loss of endogenous KAR activity. The coordinated action of these two receptor mechanisms has immediate physiological relevance in controlling presynaptic efficacy and transmission dynamics at CA3-CA1 synapses at a stage of development when functional contact already exists but transmission is weak.
TL;DR: In this review the anatomical pathways, synaptic plasticity mechanisms and structural plasticity substrates involved in cortical plasticity are explored, focusing on work in the somatosensory cortex and the barrel cortex in particular.
Abstract: Functional rehabilitation of the cortex following peripheral or central nervous system damage is likely to be improved by a combination of behavioural training and natural or therapeutically enhanced synaptic plasticity mechanisms. Experience-dependent plasticity studies in the somatosensory cortex have begun to reveal those synaptic plasticity mechanisms that are driven by sensory experience and might therefore be active during behavioural training. In this review the anatomical pathways, synaptic plasticity mechanisms and structural plasticity substrates involved in cortical plasticity are explored, focusing on work in the somatosensory cortex and the barrel cortex in particular.
TL;DR: Evidence supporting a role for NCS proteins in plasticity is brought together, focusing on emerging roles of NCS-1 and hippocalcin.
Abstract: Calcium entry plays a major role in the induction of several forms of synaptic plasticity in different areas of the central nervous system. The spatiotemporal aspects of these calcium signals can determine the type of synaptic plasticity induced, e.g. LTP (long-term potentiation) or LTD (long-term depression). A vast amount of research has been conducted to identify the molecular and cellular signalling pathways underlying LTP and LTD, but many components remain to be identified. Calcium sensor proteins are thought to play an essential role in regulating the initial part of synaptic plasticity signalling pathways. However, there is still a significant gap in knowledge, and it is only recently that evidence for the importance of members of the NCS (neuronal calcium sensor) protein family has started to emerge. The present minireview aims to bring together evidence supporting a role for NCS proteins in plasticity, focusing on emerging roles of NCS-1 and hippocalcin.
TL;DR: It is concluded that the eye and the otic vesicle are modules that may develop, to a certain degree, independently of the rest of the embryo, and it is suggested that the modularization acts as buffering mechanism against extreme developmental deviations.
Abstract: We studied early embryonic development of zebra fish and tested if changes in the external raising conditions could elicit phenotypic changes during the phylotypic stage which, classically, is considered as a conserved embryonic stage. In particular, we tested for internal constraints, plasticity, and heterochrony during the early embryonic development. Our tested hypotheses predict (i) no change associated with developmental stability/internal constraints, (ii) change of the rate of development associated with developmental flexibility, and (iii) heterochronic disruption of developmental pattern associated with a modular organization of the embryo. We measured 14 traits of embryos raised in different conditions (temperature, salinity, oxygen concentration). The results of our study show that zebra fish embryos respond flexibly to changes in external parameters even during the conserved "phylotypic stage." It also showed that internal constraints canalize early development when exposed to moderate external challenges. Hypoxic conditions, however, elicited a heterochronic delay of the onset of the development of the Anlagen of the eye and the otic vesicle from the remaining embryo. Therefore, we concluded that the eye and the otic vesicle are modules that may develop, to a certain degree, independently of the rest of the embryo. Because these modules become recognizable only under specific raising conditions, we suggest that the modularization acts as buffering mechanism against extreme developmental deviations. Our results provide support to the idea that modularity is present during the phylotypic stage, but it is not effective under normal conditions.
TL;DR: An analysis of pathways affected suggests that intrauterine programming of UN animals to favor fat as an energy source results in mitochondrial dysfunction which initially affects the postnatal hepatic function and subsequently, via the resultant metabolic changes in other organs leads to the evolution of a phenotype similar to that of the metabolic syndrome.
Abstract: A link has been established between prenatal nutrition and the development of metabolic and cardiovascular diseases later in life, a process referred to as developmental programming. It has been suggested that the trajectory of development is shifted by alterations in the maternal nutritional state leading to changes in developmental plasticity, in part underpinned by epigenetic changes in gene regulation. However, to date, only candidate gene approaches have been used to assess expression and molecular changes in the offspring of maternally undernourished animals. Furthermore, most work has focused on animals at an age where the programmed phenotype is already manifest and little is known about changes in gene expression in the offspring prior to development of obesity and related metabolic disorders. Gene expression profiles of liver, retroperitoneal white adipose fat, and biceps femoris skeletal muscle tissue from young adult male rats (55 days old) in which nutritional status had been manipulated in utero by maternal undernutrition (UN) were compared to the profiles of offspring of ad libitum fed mothers serving as the control group (AD) (8 offspring/group). The expression profiles were determined using the Illumina RatRef-12 BeadChip. No significant changes in expression were identified for skeletal muscle or white adipose tissue. However, studies of liver tissue showed 249 differentially expressed genes (143 up regulated, 106 down regulated). Although the animals at day 55 have yet to develop obesity they already show biochemical abnormalities and by day 110 express a phenotype characterized by increased adiposity and altered insulin sensitivity. An analysis of pathways affected suggests that intrauterine programming of UN animals to favor fat as an energy source results in mitochondrial dysfunction which initially affects the postnatal hepatic function and subsequently, via the resultant metabolic changes in other organs leads to the evolution of a phenotype similar to that of the metabolic syndrome.