Neuroscience and biobehavioral reviews
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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 · Oct 2014
ReviewRett syndrome and the urge of novel approaches to study MeCP2 functions and mechanisms of action.
Rett syndrome (RTT) is a devastating genetic disorder that worldwide represents the most common genetic cause of severe intellectual disability in females. Most cases are caused by mutations in the X-linked MECP2 gene. Several recent studies have demonstrated that RTT mimicking animal models do not develop an irreversible condition and phenotypic rescue is possible. ⋯ Herein, we thoroughly survey the knowledge about MeCP2 structure and functions, highlighting the necessity of identifying more functional domains and the value of molecular genetics. Given that, in our opinion, RTT ultimately is generated by perturbations in gene transcription and so far no genes/pathways have been consistently linked to a dysfunctional MeCP2, we have used higher-level bioinformatic analyses to identify commonly deregulated mechanisms in MeCP2-defective samples. In this review we present our results and discuss the possible value of the utilized approach.
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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.