, 2009; Hermida et al., 2014), asthma (Smolensky et al., 1987; Nainwal, 2012) and rheumatoid arthritis (Cutolo, 2012). Given that differences in the timing of symptoms for many conditions are similar across individuals, implementing chronotherapeutic strategies for the treatment of some diseases is quite feasible and researchers and pharmaceutical
companies are developing strategies to effectively deliver medications in a time-dependent fashion thorough time-release oral administration, implants, and pumps (reviewed in Maroni et al., 2010). Given the rapid advances in this emerging knowledge and technology, it will be important to educate the medical community in the magnitude of such check details effects and practical implementation of chronotherapeutic approaches. The cells of our brains and bodies have evolved in selleckchem a 24 h solar system in ways that enable optimal coordination of our internal and external circadian cycles. Transcription–translation feedback loops are modified by post-transcriptional regulatory processes, enabling a central master clock to signal peripheral clocks that then exert local control of cellular function specific to each organ
and gland. Making optimal use of circadian timing mechanisms within specific brain regions and tissues will enable the understanding of interindividual differences and development of pharmacological modulators of circadian timing identified from high-throughput screens. The hope is that the robustness and resilience of circadian oscillation can be enhanced, dysfunctional clocks can be repaired, and personalized treatment regimens
developed for age-related declines and treatment of disease. Further information on mechanisms whereby the SCN signals rhythmic gene expression in the rest of the brain and body requires new genetic, mathematical and statistical tools to understand the spatial and temporal changes in the circadian timing system that underlie its normal and disrupted neural function. We thank Dr Matthew Butler Ribonucleotide reductase and unidentified reviewers for their comments on earlier drafts of this article. Support during the writing of this review and research from our laboratories reported herein was provided by NSF IOS-1256105 and NIH NS37919 (R.S.), and NIH HD050470 and NSF IOS-1257638 (L.J.K.). Abbreviations Cry cryptochrome DMH dorsomedial hypothalamus FAA food anticipatory activity LD light:dark Per Period ROR retinoid-related orphan receptor SCN suprachiasmatic nucleus VLPO ventrolateral preoptic nucleus “
“Clinical evidence suggests that depression and trauma predispose the subject to panic. Accordingly, here we examined the late effects of uncontrollable stress, a presumptive model of depression and/or traumatic disorder, on panic-like behaviors evoked by electrical stimulation of the dorsal periaqueductal gray (DPAG).