Biology subjects

Garza, K. M.

Publications and source records attributed to Garza, K. M..

3 recordsLinked to original sources

bioRxiv2023

Brain rhythms control microglial response and cytokine expression via NFkappaB signaling

Microglia, the brains primary immune cells, transform in response to changes in sensory or neural activity, like sensory deprivation. However, little is known about how specific frequencies of neural activity, or brain rhythms, impact microglia and cytokine signaling. Using visual noninvasive flickering sensory stimulation (flicker) to induce electrical neural activity at different frequencies, 40Hz, within the gamma band and 20Hz, within the beta band, we discovered these brain rhythms differentially affect microglial morphology and cytokine expression in healthy animals. We found that flicker induced expression of certain cytokines, including IL-10 and M-CSF, that was independent of microglia. Because NF{kappa}B is activated by synaptic activity and regulates cytokines, we hypothesized this pathway plays a causal role in frequency-specific cytokine and microglial responses. Indeed, we found that after flicker, phospho-NF{kappa}B co-labeled with neurons more than microglia. Furthermore, inhibition of NF{kappa}B signaling by a small molecule inhibitor down-regulated flicker-induced cytokine expression and attenuated flicker-induced changes in microglia morphology. These results reveal a new mechanism through which brain rhythms affect brain function by altering microglia morphology and cytokines via NF{kappa}B. TeaserFrequency-specific brain rhythms regulate cytokine expression, microglia morphology, and microglia-independent expression of M-CSF and IL10 via NF{kappa}B.

neuroscience↗

bioRxiv2023

RNA in extracellular vesicles during adolescence reveal immune, energetic and microbial imprints of early life adversity.

Exposure to early life adversity (ELA), including childhood maltreatment, is one of the most significant risk factors for the emergence of neuropsychiatric disorders in adolescence and adulthood. Despite this relationship being well established, the underlying mechanisms remain unclear. One way to achieve this understanding is to identify molecular pathways and processes that are perturbed as a consequence of childhood maltreatment. Ideally, these perturbations would be evident as changes in DNA, RNA or protein profiles in easily accessible biological samples collected in the shadow of childhood maltreatment. In this study, we isolated circulating extracellular vesicles (EVs) from plasma collected from adolescent rhesus macaques that had either experienced nurturing maternal care (CONT) or maternal maltreatment (MALT) in infancy. RNA sequencing of RNA in plasma EVs and gene enrichment analysis revealed that genes related to translation, ATP synthesis, mitochondrial function and immune response were downregulated in MALT samples, while genes involved in ion transport, metabolism and cell differentiation were upregulated. Interestingly, we found that a significant proportion of EV RNA aligned to the microbiome and that MALT altered the diversity of microbiome-associated RNA signatures found in EVs. Part of this altered diversity suggested differences in prevalence of bacterial species in CONT and MALT animals noted in the RNA signatures of the circulating EVs. Our findings provide evidence that immune function, cellular energetics and the microbiome may be important conduits via which infant maltreatment exerts effects on physiology and behavior in adolescence and adulthood. As a corollary, perturbations of RNA profiles related to immune function, cellular energetics and the microbiome may serve as biomarkers of responsiveness to ELA. Our results demonstrate that RNA profiles in EVs can serve as a powerful proxy to identify biological processes that might be perturbed by ELA and that may contribute to the etiology of neuropsychiatric disorders in the aftermath of ELA.

zoology↗

bioRxiv2020

Sex-specific calibration of memory recall by glucocorticoid receptors on cortical astrocytes

Dysfunctions in memory recall lead to pathological fear; a hallmark of trauma-related disorders, like Post-Traumatic Stress Disorder (PTSD). Heightened recall of an association between a cue and trauma, as well as impoverished recall that a previously trauma-related cue is no longer a threat both result in a debilitating fear toward the cue. Glucocorticoid-mediated action via the glucocorticoid receptor (GR) influences memory recall. This literature has primarily focused on GRs expressed in neurons or ignored cell-type specific contributions. To ask how GR action in non-neuronal cells influences memory recall, we combined auditory fear conditioning in mice and the knockout of GRs in astrocytes in the prefrontal cortex (PFC), a brain region implicated in memory recall. We found that GRs in astrocytes in the PFC calibrate recall in female but not male mice. Specifically, we found that knocking out GRs in astrocytes in the PFC of female mice (AstroGRKO) after fear conditioning resulted in higher recall of fear to the CS+ tone when compared to controls (AstroGRintact). While we did not find any differences in extinction of fear toward the CS+ between these groups, AstroGRKO female mice showed impaired recall of extinction training. We did not observe any significant results in male mice. These results suggest a sex-specific calibration of memory recall by GRs in astrocytes in the PFC. These data demonstrate the need to examine GR action in cortical astrocytes to elucidate the basic neurobiology underlying memory recall and potential mechanisms that underlie female-specific biases in the incidence of PTSD.

neuroscience↗