Biology subjects

Martz, J.

Publications and source records attributed to Martz, J..

4 recordsLinked to original sources

bioRxiv2025

Investigating milk derived extracellular vesicles as mediators of maternal stress and environmental intervention

Parental communication signals are transmitted through nursing and critically shape neurodevelopmental trajectories. Mirroring some well characterized effects of gestational challenges in rodents, maternal immune activation (MIA) during the lactational period disrupts maternal physiology, decreases lipid content, and is associated with adverse neurobehavioral outcomes in offspring. This occurs without MIA significantly affecting maternal care. While gestational MIA models are responsive to environmental interventions, which beneficially alter maternal milk composition and associated offspring outcomes, the bioactive mediators in milk underlying resilience remain poorly understood. Milk-derived extracellular vesicles (MEVs) transport and deposit biologically active cargo, including microRNAs (miRNAs) that induce post-translational regulation of candidate mRNA in the nursing offsprings tissues and cells. Using a rat model, we show that lactational MIA alters MEV-miRNA cargo and the expression of hippocampal miRNAs in offspring. Several miRNAs in MEVs were also found in the hippocampus of matching offspring. Remarkably, the miRNA changes in MEVs and the neonatal hippocampus were rescued when dams were raised in an enriched environment, suggesting environmental enrichment protected from the effects of MIA. This was supported by the behavioral phenotype. RNA-seq of adult offspring hippocampus showed long-term transcriptional changes associated with the gene targets of early-life regulated miRNAs. Our results position MEV-miRNA as dynamic programming signals by which maternal experience is communicated to offspring, encoding both stress-induced and protective cues that influence development. This suggests that breastfeeding interventions can regulate the genetic cargo of the milk, programming the life of developing infants.

neuroscience↗

bioRxiv2024

Peripubertal antagonism of corticotropin-releasing factor receptor 1 results in sustained, sex-specific changes in behavioral plasticity and the transcriptomic profile of the amygdala

Peripuberty is a significant period of neurodevelopment with long-lasting effects on the brain and behavior. Blocking type 1 corticotropin-releasing factor receptors (CRFR1) in neonatal and peripubertal rats attenuates detrimental effects of early-life stress on neural plasticity, behavior, and stress hormone action, long after exposure to the drug has ended. CRFR1 antagonism can also impact neural and behavioral development in the absence of stressful stimuli, suggesting sustained alterations under baseline conditions. To investigate this further, we administered the CRFR1 antagonist (CRFR1a) R121919 to young adolescent male and female rats across 4 days. Following each treatment, rats were tested for locomotion, social behavior, mechanical allodynia, or prepulse inhibition (PPI). Acute CRFR1 blockade immediately reduced PPI in peripubertal males, but not females. In adulthood, each assay was repeated without CRFR1a exposure to test for persistent effects of the adolescent treatment. Males continued to experience deficits in PPI while females displayed altered locomotion, PPI, and social behavior. The amygdala was collected to measure long-term effects on gene expression. In the adult amygdala, peripubertal CRFR1a induced alterations in pathways related to neural plasticity and stress in males. In females, pathways related to central nervous system myelination, cell junction organization, and glutamatergic regulation of synaptic transmission were affected. Understanding how acute exposure to neuropharmacological agents can have sustained impacts on brain and behavior, in the absence of further exposures, has important clinical implications for developing adolescents.

neuroscience↗

bioRxiv2023

Sex differences in offspring risk and resilience following 11β-hydroxylase antagonism in a rodent model of maternal immune activation

Maternal immune activation (MIA) puts offspring at greater risk for neurodevelopmental disorders associated with impaired social behavior. While it is known that immune signaling through maternal, placental, and fetal compartments contributes to these phenotypical changes, it is unknown to what extent the stress response to illness is involved and how it can be harnessed for potential interventions. To this end, on gestational day 15, pregnant rat dams were administered the bacterial mimetic lipopolysaccharide (LPS; to induce MIA) alongside metyrapone, a clinically available 11{beta}-hydroxylase inhibitor used to treat hypercortisolism in pregnant and neonatal populations. Maternal, placental, and fetal CNS levels of corticosterone and placental 11{beta}HSD enzymes type 1 and 2 were measured 3-hrs post treatment. Offspring social behaviors were evaluated across critical phases of development. MIA was associated with increased maternal, placental, and fetal CNS corticosterone concentrations that were diminished with metyrapone exposure. Metyrapone protected against reductions in placental 11{beta}HSD2 in males only, suggesting that less corticosterone was inactivated in female placentas. Behaviorally, metyrapone-exposure attenuated MIA-induced social disruptions in juvenile, adolescent, and adult males, while females were unaffected or performed worse. Metyrapone-exposure reversed MIA-induced transcriptional changes in monoamine-, glutamate-, and GABA-related genes in the ventral hippocampus of adult males, but not females. Taken together, these findings illustrate that MIA-induced HPA responses act alongside the immune system to produce behavioral deficits. As a clinically available drug, the sex-specific benefits and constraints of metyrapone should be investigated further as a potential means of reducing neurodevelopmental risks due to gestational MIA.

neuroscience↗

bioRxiv2023

A critical role of a eubiotic microbiota in gating proper immunocompetence in Arabidopsis

Although many studies have shown that microbes can ectopically stimulate or suppress plant immune responses, the fundamental question of whether the entire preexisting microbiota is indeed required for proper development of plant immune response remains unanswered. Using a recently developed peat-based gnotobiotic plant growth system we found that Arabidopsis grown in the absence of a natural microbiota lacked age-dependent maturation of plant immune response and were defective in several aspects of pattern-triggered immunity. Axenic plants exhibited hypersusceptibility to infection by the bacterial pathogen Pseudomonas syringae pv. tomato DC3000 and the fungal pathogen Botrytis cinerea. Microbiota-mediated immunocompetence was suppressed by rich nutrient conditions, indicating a tripartite interaction between the host, microbiota, and abiotic environment. A synthetic microbiota composed of 48 culturable bacterial strains from the leaf endosphere of healthy Arabidopsis plants was able to substantially restore immunocompetence similar to plants inoculated with a soil-derived community. In contrast, a 52-member dysbiotic synthetic leaf microbiota overstimulated the immune transcriptome. Together, these results provide evidence for a causal role of a eubiotic microbiota in gating proper immunocompetence and age-dependent immunity in plants.

plant biology↗