The current study used two inbred mouse strains, C57BL/6 J and A/J, to investigate the genetics of behavioral responses to fentanyl. Mice were tested for conditioned place preference and fentanyl-induced locomotor activity. C57BL/6J mice formed a conditioned place preference to fentanyl injections and fentanyl increased their activity. Neither effect was noted in A/J mice. We conducted RNA-sequencing on the nucleus accumbens of mice used for fentanyl-induced locomotor activity. Surprisingly, we noted few differentially expressed genes using treatment as the main factor. However many genes differed between strains.
Authors:
Samuel J Harp, Mariangela Martini, Will Rosenow, Larry D Mesner, Hugh Johnson, Charles R Farber, Emilie F Rissman
Alcohol transcriptome changes in mice microglia total homogenate p-value
Description:
Microglia are fundamentally important immune cells within the central nervous system (CNS) that respond to environmental challenges to maintain normal physiological processes. Alterations in steady-state cellular function and over-activation of microglia can facilitate the initiation and progression of neuropathological conditions such as Alzheimer’s disease, Multiple Sclerosis, and Major Depressive Disorder. Alcohol consumption disrupts signaling pathways including both innate and adaptive immune responses that are necessary for CNS homeostasis. Coordinate expression of these genes is not ascertained from an admixture of CNS cell-types, underscoring the importance of examining isolated cellular populations to reveal systematic gene expression changes arising from mature microglia. Unbiased RNA-Seq profiling was used to identify gene expression changes in isolated prefrontal cortical microglia in response to recurring bouts of voluntary alcohol drinking behavior. The voluntary ethanol paradigm utilizes long-term consumption ethanol that results in escalated alcohol intake and altered cortical plasticity that is seen in humans. Gene coexpression analysis identified a coordinately regulated group of genes, unique to microglia, that collectively are associated with alcohol consumption. Genes within this group are involved in toll-like receptor signaling and transforming growth factor beta signaling. Network connectivity of this group identified Siglech as a putative hub gene and highlighted the potential importance of proteases in the microglial response to chronic ethanol. In conclusion, we identified a distinctive microglial gene expression signature for neuroimmune responses related to alcohol consumption that provides valuable insight into microglia-specific changes underlying the development of substance abuse, and possibly other CNS disorders.
Authors:
Gizelle M McCarthy, Sean P Farris, Yuri A Blednov, R Adron Harris, R Dayne Mayfield
Genes with particular expression in the Anterior olfactory nucleus, dorsal part. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Accessory olfactory bulb. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Accessory olfactory bulb, glomerular layer. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Orbital area, lateral part, layer 1. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Flocculus, granular layer. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Orbital area, ventrolateral part, layer 1. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Nucleus of the lateral lemniscus, dorsal part. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Granular lamina of the cochlear nuclei. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Koelliker-Fuse subnucleus. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Agranular insular area, posterior part, layer 2/3. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Anterior olfactory nucleus, external part. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Anterior olfactory nucleus, lateral part. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Accessory olfactory bulb, granular layer. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Medial vestibular nucleus. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Accessory olfactory bulb, mitral layer. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Anterior pretectal nucleus. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Ventrolateral preoptic nucleus. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Nucleus of the solitary tract, medial part. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Basolateral amygdalar nucleus. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Basolateral amygdalar nucleus, anterior part. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Basolateral amygdalar nucleus, posterior part. Data represent fold expression difference in structure versus grey matter average expression.
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