Neuroscience and biobehavioral reviews
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Neurosci Biobehav Rev · Oct 2014
ReviewEarly-life risk factors for panic and separation anxiety disorder: insights and outstanding questions arising from human and animal studies of CO2 sensitivity.
Genetically informative studies showed that genetic and environmental risk factors act and interact to influence liability to (a) panic disorder, (b) its childhood precursor separation anxiety disorder, and (c) heightened sensitivity to CO2, an endophenotype common to both disorders. Childhood adversities including parental loss influence both panic disorder and CO2 hypersensitivity. ⋯ Animal findings paralleled those of human studies, in that different forms of early maternal separation in mice and rats evoked heightened CO2 sensitivity; in mice, this could be explained by gene-by-environment interactional mechanisms. While several questions and issues (including obvious divergences between humans and rodents) remain open, parallel investigations by contemporary molecular genetic tools of (1) human longitudinal cohorts and (2) animals in controlled laboratory settings, can help elucidate the mechanisms beyond these phenomena.
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Neurosci Biobehav Rev · Oct 2014
ReviewTranslational approach to studying panic disorder in rats: hits and misses.
Panic disorder (PD) patients are specifically sensitive to 5–7% carbon dioxide. Another startling feature of clinical panic is the counterintuitive lack of increments in ‘stress hormones’. ⋯ In line with prior studies showing that DPAG-evoked panic-like behaviours are attenuated by clinically-effective treatments with panicolytics, we show here that (i) the DPAG harbors a hypoxia-sensitive alarm system, which is activated by hypoxia and potentiated by hypercapnia, (ii) the DPAG suffocation alarm system is inhibited by clinically-effective treatments with panicolytics, (iii) DPAG stimulations do not increase stress hormones in the absence of physical exertion, (iv) DPAG-evoked panic-like behaviours are facilitated in neonatally-isolated adult rats, a model of CSA, and (v) DPAG-evoked responses are enhanced in the late diestrus of female rats. Data are consistent with the DPAG mediation of both respiratory and non-respiratory types of panic attacks.
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Neurosci Biobehav Rev · Sep 2014
ReviewEpigenetics: the neglected key to minimize learning and memory deficits in Down syndrome.
Down syndrome (DS) is the most common genetic intellectual disability, caused by the triplication of the human chromosome 21 (HSA21). Although this would theoretically lead to a 1.5 fold increase in gene transcription, transcript levels of many genes significantly deviate. Surprisingly, the underlying cause of this gene expression variation has been largely neglected so far. ⋯ Importantly, epigenetic marks are reversible, offering a huge therapeutic potential to alleviate or cure certain genetic deficits. Current epigenetic therapies are already used for cancer and epilepsy, and might provide novel possibilities for cognition-enhancing treatment in DS as well. To that end, this review discusses the still limited knowledge on epigenetics in DS and describes the potential of epigenetic therapies to reverse dysregulated gene expression.
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Neurosci Biobehav Rev · Sep 2014
ReviewModulating the delicate glial-neuronal interactions in neuropathic pain: promises and potential caveats.
During neuropathic pain, glial cells (mainly astrocytes and microglia) become activated and initiate a series of signaling cascades that modulate pain processing at both spinal and supraspinal levels. It has been generally accepted that glial cell activation contributes to neuropathic pain because glia release proinflammatory cytokines, chemokines, and factors such as calcitonin gene-related peptide, substance P, and glutamate, which are known to facilitate pain signaling. ⋯ Accordingly, use of glial inhibitors might compromise the protective functions of glia in addition to suppressing their detrimental effects. With a better understanding of how different conditions affect glial cell activation, we may be able to promote the protective function of glia and pave the way for future development of novel, safe, and effective treatments of neuropathic pain.