Abstract
FosB gene heterodimerizes with Jun family proteins to form activator protein 1 (AP-1) complexes that bind to AP-1 sites in responsive genes to regulate transcription in all cells. The genic expression of FosB seems to be modified after long time exposure to drugs of abuse and these changes may be involved in craving and addicted behavior. This study investigated the FosB mRNA expression in peripheral blood lymphocytes of drug addicted patients using real-time PCR approach. Thus, patients with crack-cocaine use disorder (CUD, n = 10), alcohol use disorder (AUD, n = 12), and healthy non-addicted subjects (CONT, n = 12) were assessed. FosB mRNA expression was reduced by 1.15-fold in CUD and 2.17-fold in AUD when compared to CONT. Hedge’s effect size gs over log FosB/Act was of 0.66 for CUD and of 0.30 for AUD when compared to controls. This study showed that FosB mRNA expression was detected in lymphocytes from peripheral blood for the first time, and it was less expressed in drug addicted patients. This molecular technique may constitute a potential peripheral marker for substance use disorder.
Highlights
The use of addictive drugs has been associated with alteration of gene expression in the brain that result in long-term changes on synapses and neural circuits and consequent neuroadaptive and behavioral changes such as tolerance and craving, which may underlie the development and maintenance of drug addiction (Nestler, 2008; Gajewski et al, 2016).FosB gene heterodimerizes with Jun family proteins to form activator protein 1 (AP-1) complexes that bind to AP-1 sites in responsive genes to regulate transcription in all cells
Schooling was found different among groups (p < 0.05) possibly because of higher proportion of middle school degree in alcohol use disorder patients (AUD) patients when compared to higher school degree in control and CUD patients; employment situation was different among groups (p = 0.001) as larger proportion of CUD and AUD patients was unemployed and/or working as freelancers and smaller proportion of them was formally employed; and marital state was different among groups (p < 0.01) as higher proportion was married or living in common law in control and AUD groups, whereas CUD patients were mostly single or widow (Table 1)
According to “peripheral marker hypothesis,” changes in genetics expression in the brain are reflected in peripheral blood lymphocytes (Roozafzoon et al, 2010)
Summary
The use of addictive drugs has been associated with alteration of gene expression in the brain that result in long-term changes on synapses and neural circuits and consequent neuroadaptive and behavioral changes such as tolerance and craving, which may underlie the development and maintenance of drug addiction (Nestler, 2008; Gajewski et al, 2016).FosB gene heterodimerizes with Jun family proteins to form activator protein 1 (AP-1) complexes that bind to AP-1 sites in responsive genes to regulate transcription in all cells. The use of addictive drugs has been associated with alteration of gene expression in the brain that result in long-term changes on synapses and neural circuits and consequent neuroadaptive and behavioral changes such as tolerance and craving, which may underlie the development and maintenance of drug addiction (Nestler, 2008; Gajewski et al, 2016). According to Nestler (2012), drugs of abuse actives excitatory synapses increasing Ca2+ channels permeability into the neuron, triggering intracell targets to induce up or down regulation of genic expression. These alteration of genic expression in target genes like CREB, BDNF, and FosB would be involved in the development of a “state of addiction” (Nestler, 2013). A truncated product of the FosB gene, the delta-FosB, gradually accumulates trough a course of repeated exposure to virtually all drugs of abuse and because of its unusual stability, its levels persist for weeks after drug cessation, mediating the sensitized responses to drug exposure (Nestler, 2008, 2013)
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