Stress 101

Eustress, Hormesis, Distress. Spot the differences!

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Iactate, biosis

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Anterior pituitaries of the rainbow trout (Oncorhynchus mykiss) were incubated with graded concentrations of arginine vasotocin (AVT) or synthetic rat corticotrophin-releasing hormone (rCRH-41),...

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An alternative approach to regulating Nrf2-dependent gene expression is through targeting the transcriptional repressor Bach1. Bach1 is a member of the BTB and CNC transcriptional regulator family that, like Nrf2, binds to ARE sequences as heterodimeric complexes with small Maf proteins [18] A major physiological role for Bach1 is in iron homeostasis through regulation of the expression of heme oxygenase-1 (HMOX1), ferroportin (FPN1) and Ferritin (FTH) genes[23], [24], [33], [41]. Elevation of intracellular hemin leads to induction of HMOX1 enzyme activity. Consequently, hemin is converted to carbon monoxide, bilirubin and free iron. As hemin levels are reduced, Bach1 is resynthesized and repression of HMOX1 and other genes is restored. Thus Bach1 coordinates the overall intracellular levels of hemin and iron metabolizing genes with anti-oxidant gene expression [19], [21], [22], [24].

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A hierarchical hormonal cascade along the HPA axis orchestrates bodily responses to stress. 

Although CRH produced by parvocellular neurons of the hypothalamic paraventricular nucleus (PVN) and released into the portal circulation at the median eminence, is known to prime downstream hormone release, the molecular mechanism regulating phasic CRH release remains poorly understood.

Here, we find a cohort of parvocellular cells interspersed with magnocellular PVN neurons expressing secretagogin.

Single-cell transcriptome analysis combined with protein interactome profiling identifies secretagogin neurons as a distinct CRH-releasing neuron population reliant on secretagogin's Ca(2+) sensor properties and protein interactions with the vesicular traffic and exocytosis release machineries to liberate this key hypothalamic releasing hormone.

Pharmacological tools combined with RNA interference demonstrate that secretagogin's loss of function occludes adrenocorticotropic hormone release from the pituitary and lowers peripheral corticosterone levels in response to acute stress.

 Cumulatively, these data define a novel secretagogin neuronal locus and molecular axis underpinning stress responsiveness. 

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The secret of empathy: Stress from the presence of strangers prevents empathy, in both mice and humans

The ability to express empathy -- the capacity to share and feel another's emotions -- is limited by the stress of being around strangers, according to a new study. Empathy is increasingly being studied by scientists because of its known role in psychological disorders, such as Autism Spectrum Disorder and psychopathy.

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Neurobiol Learn Mem. 2009 May;91(4):333-42. doi: 10.1016/j.nlm.2008.11.003. Epub 2008 Dec 18. Research Support, Non-U.S. Gov't; Review

[fish-i-ology]

Drug addiction can be defined by a three-stage cycle

binge/intoxication

withdrawal/negative affect

preoccupation/anticipation 

CRF, corticotropin-releasing factor

dynorphin-κ opioid systems in the ventral striatum, extended amygdala, and frontal cortex (both between-system opponent processes

 Neuropeptide Y, a powerful anti-stress neurotransmitter, has a profile of action on compulsive-like responding for ethanol similar to a CRF1 antagonist. 

The loss of reward function and recruitment of brain systems provide a powerful neurochemical basis that drives the compulsivity of addiction.

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