Neuroscience
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Peroxisome proliferator-activated receptor (PPAR)-γ and PPARα have shown neuroprotective effects in models of Parkinson's disease (PD). The role of the third, more ubiquitous isoform PPARδ has not been fully explored. This study investigated the role of PPARδ in PD using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to model the dopaminergic neurodegeneration of PD. ⋯ PPARδ heterozygous mice were not protected against MPTP toxicity. Intra-striatal infusion of GW0742 (84 μg/day) reduced the MPTP-induced loss of dopaminergic neurons (5036±195) when compared to vehicle-infused mice (3953±460). These results indicate that agonism of PPARδ provides protection against MPTP toxicity, in agreement with the effects of other PPAR agonists.
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Perceptions, thoughts, emotions and actions emerge from interactions between neuronal assemblies distributed across the brain rather than from local computations in restricted brain areas. Indeed, the operation of every cognitive act requires the integration of distributed activity, as implemented through long-range neuronal communication via a network of structural connections. Functional interactions in the brain are very often studied in subjects at rest, since the resting state is a privileged condition in which brain activity is unbiased by any specific goal-directed task. ⋯ Multimodal studies have begun to disclose relationships between functional connectivity, as revealed by hemodynamic signals, and underlying electrophysiological processes. Furthermore, functional connectivity studies directly based on electrophysiological signals have recently revealed fundamental information regarding long-range neuronal communication at behaviorally relevant time-scales. The integration of different lines of evidence from hemodynamic and electrophysiological studies suggests that rapid changes of synchronized oscillatory activity in distributed brain networks is relevant for the ongoing maintenance and modulation of the task representations that form the basis of our cognitive flexibility.
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Peripheral nerves, essential connections between the brain, spinal cord and body, do not regenerate as well as generally reported. Identifying new strategies to facilitate regeneration is essential to reversing neurological deficits from nerve injuries or disease. ⋯ Knockdown or inhibition of PTEN is associated with robust sprouting of adult sensory neurons in vitro and in vivo, additive to the accelerated outgrowth offered by the preconditioning effect. This sprouting response, if spatially and temporally constrained, may provide potent regrowth initiation, of interest in otherwise untreatable nerve damage.
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The medial prefrontal cortex (mPFC) has emerged as a key structure involved in the modulation of fear behavior over the past few decades. Anatomical, functional and electrophysiological studies have begun to shed light on the precise mechanisms by which different prefrontal regions regulate the expression and inhibition of fear behavior. ⋯ The recent development of sophisticated approaches such as large scale neuronal recordings, simultaneous multisite recordings of spiking activity and local field potentials (LFPs) along with optogenetic approaches will facilitate the testing of these new hypotheses in the near future. Here we provide an extensive review of the literature on the role of mPFC in fear behavior and propose further directions to dissect the contribution of specific prefrontal neuronal elements and circuits in the regulation of fear behavior.
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Animal models are vital tools to study the genetic, molecular, cellular, and environmental parameters involved in several neuropsychiatric disorders. Over the years, these models have expanded our understanding of the pathogenesis of many neuropsychiatric disorders and neurodegenerative diseases. Although animal models have been widely used in psychiatry, and despite several years of extensive research with these models, their validity is still being investigated and presents a challenge to both investigators and clinicians as well. ⋯ In addition, we will also discuss the validity and reliability of these models and current challenges in this domain. Furthermore, this work will discuss the role of gene-environment interaction as an additional contributing factor that modulates neuropsychological outcome and its implication on animal models. This overview will give a succinct summary of animal models in psychiatry which will be useful both to the seasoned researcher, as well as novices in the field.