Biology subjects

Rybicki, A.

Publications and source records attributed to Rybicki, A..

2 recordsLinked to original sources

bioRxiv2024

DJ-1 mediates regulation of metabolism and immune response in Parkinsons disease astrocytes and Glioblastoma cells

An inverse correlation for the expression of Parkinsons disease (PD)- and cancer-associated genes has been previously reported. Genes that are upregulated in cancer are frequently downregulated in PD and vice versa. PARK7, encoding DJ-1, was initially identified as an oncogene, but loss of DJ-1 causes early-onset PD. However, it remains elusive how differential DJ-1 levels contribute to opposite cell fates in cancer and PD. Here, we demonstrate specific effects of differential DJ-1 protein levels on the energy metabolism and cell growth in patient-derived cellular models of PD and glioblastoma (GBM) cell lines. Impaired energy metabolism was associated with an increased immune response upon IL-1{beta} stimulation and increased apoptosis and decreased cell growth in models of PD, whereas in GBM cells increased metabolic activity translated into a reduced immune response and increased cell growth. Furthermore, we found decreased glutathione (GSH) synthesis and therefore increased levels of reactive oxygen species (ROS) and oxidized glutathione (GSSG) in models of DJ-1 deficiency and decreased ROS levels in GBM cell lines. Thus, the mechanism by which DJ-1 modulates these phenotypes is the same in both diseases. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=84 SRC="FIGDIR/small/621212v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@4eccb4org.highwire.dtl.DTLVardef@161669corg.highwire.dtl.DTLVardef@197bfc3org.highwire.dtl.DTLVardef@1aecb36_HPS_FORMAT_FIGEXP M_FIG C_FIG DJ-1 levels modulate GSSG/GSH ratio and ROS levels, which results in divergent effects on cell growth and immune response in DJ-1-dependent glial pathologies in glioblastoma and PD. In models of PD, DJ-1 level dependent phenotypes can be rescued by antioxidant treatment that reduces the GSSG/GSH ratio and ROS levels.

neuroscience↗

bioRxiv2021

Dopaminergic challenge dissociates learning from primary versus secondary sources of information

Some theories of human cultural evolution posit that humans have social-specific learning mechanisms that are adaptive specialisations moulded by natural selection to cope with the pressures of group living. However, the existence of neurochemical pathways that are specialised for learning from social information and from individual experience is widely debated. Cognitive neuroscientific studies present mixed evidence for social-specific learning mechanisms: some studies find dissociable neural correlates for social and individual learning whereas others find the same brain areas and, dopamine-mediated, computations involved in both. Here we demonstrate that, like individual learning, social learning is modulated by the dopamine D2 receptor antagonist haloperidol when social information is the primary learning source, but not when it comprises a secondary, additional element. Two groups (total N = 43) completed a decision-making task which required primary learning, from own experience, and secondary learning from an additional source. For one group the primary source was social, and secondary was individual; for the other group this was reversed. Haloperidol affected primary learning irrespective of social/individual nature, with no effect on learning from the secondary source. Thus, we illustrate that neurochemical mechanisms underpinning learning can be dissociated along a primary-secondary but not a social-individual axis. These results resolve conflict in the literature and support an expanding field showing that, rather than being specialised for particular inputs, neurochemical pathways in the human brain can process both social and non-social cues and arbitrate between the two depending upon which cue is primarily relevant for the task at hand.

neuroscience↗