Biology subjects

Dickson, D. A.

Publications and source records attributed to Dickson, D. A..

2 recordsLinked to original sources

bioRxiv2023

Preimplantation Embryos Amplify Sperm-Derived miRNA Levels to Mediate Transgenerational Epigenetic Inheritance

The effects of chronically stressing male mice can be transmitted across generations by stress-specific changes in their sperm miRNA content that induce stress-specific phenotypes in their offspring. But how each stress paradigm alters the levels of distinct sets of sperm miRNAs is not known. We showed previously that exposure of male mice to chronic social instability (CSI) stress results in elevated anxiety and reduced sociability specifically in their female offspring across multiple generations because it reduces miR-34c levels in sperm of stressed males and their unstressed male offspring. Here we describe evidence that astrocyte-derived exosomes (A-Exos) carrying miR-34c mediate how CSI stress has this transgenerational effect on sperm. We found that CSI stress decreases miR-34c carried by A-Exos in the prefrontal cortex and amygdala, as well as in the blood of males. Importantly, miR-34c A-Exos levels are also reduced in these tissues in their F1 male offspring, who despite not being exposed to stress exhibit reduced sperm miR-34c levels and transmit the same stress-associated traits to their male and female offspring. Furthermore, restoring A-Exos miR-34c content in the blood of CSI-stressed males by intravenous injection of miR-34c-containing A-Exos restores miR-34c levels in their sperm. These findings reveal an unexpected role for A-Exos in maintaining sperm miR-34c levels by a process that when suppressed by CSI stress mediates this example of transgenerational epigenetic inheritance.

genetics↗

bioRxiv2020

Ras-GRF1 in CRF Cells Controls the Early Adolescent Female Response to Repeated Stress

Ras-GRF1 (GRF1) is a calcium-stimulated guanine-nucleotide exchange factor that activates Ras and Rac GTPases. In hippocampal neurons, it mediates the action of NMDA and calcium-permeable AMPA glutamate receptors on specific forms of synaptic plasticity, learning, and memory in both male and female mice. Recently, we showed that GRF1 also regulates the HPA axis response to restraint stress, but only in female mice before puberty. In particular, we found that after exposure to 7-days of restraint-stress (7DRS) (30 min/day) elevation of serum CORT levels are suppressed in early adolescent (EA) female, but not EA male or adult female GRF1 knockdown mice. Here, we show that this phenotype is due, at least in part, to the loss of GRF1 expression in CRF cells of the paraventricular nucleus of the hypothalamus, as GRF1 knockdown specifically in these cells also reduces serum CORT response to 7DRS in EA females, but not EA males or adult females. Moreover, it reduces females CORT levels to those to found in comparably stressed control male mice. GRF1 knockdown in CRF cells also blocks the anxiolytic phenotype normally found in EA females 24 hrs after 7DRS. Interestingly, loss of GRF1 in these cells has no effect after only 3 exposures to restraint stress, revealing a role for GRF1 in repeated stress-induced CRF cell plasticity that appears to be specific to EA female mice. Overall, these findings indicate that GRF1 in CRF cells makes a key contribution to the distinct response early-adolescent female display to repeated stress.

neuroscience↗