Biology subjects

Boettcher, C.

Publications and source records attributed to Boettcher, C..

3 recordsLinked to original sources

bioRxiv2025

The development of trait anxiety in nonhuman primates during the first year of life

Anxious Temperament (AT) is a nonhuman primate phenotype that models childhood behavioral inhibition, a prominent risk factor for anxiety disorders and stress-related psychopathology. To understand its earliest antecedents, we characterized ATs developmental trajectory over the first year of life. Infant monkeys (n=35, 24 female) were longitudinally phenotyped for AT by assessing threat-related increases in freezing behavior, reductions in coo-calling, and increases in circulating cortisol at 1.5, 6, 12, 24, and 52 weeks. AT levels increased linearly, reaching mature levels by 52 weeks. Individual differences in AT, and its components, were stable across development. These findings support further studies during early primate life aimed to uncover neurobiological factors mediating development of this phenotype, which in humans is linked to stress-related psychopathology.

animal behavior and cognition↗

bioRxiv2024

Single-cell variations of circadian clock and immune gene expression in microglia and neurodegeneration

We investigated the diurnal rhythmicity of gene expression in microglia, the resident macrophages of the brain, in health and disease. Using RNA sequencing and single-cell analysis by RNAscope, we examined wild-type mice and the R6/2 transgenic mouse model of Huntingtons disease (HD). Our findings suggest context-dependent rhythmic gene expression in microglia, exhibiting substantial variability between individual cells and brain regions over 24 hours. Notably, we observed loss of rhythmic gene expression of key clock genes in microglia from symptomatic but not presymptomatic R6/2 mice. Moreover, we identified de novo 24-hour rhythmic gene expression and altered diurnal patterns of immune-related genes associated with neurodegenerative diseases in microglia from symptomatic R6/2 mice. Our findings suggest circadian reprogramming of microglia in the context of neurodegeneration.

neuroscience↗

bioRxiv2020

Apple peel and flesh contain pro-neurogenic compounds

As mammals evolved exposed to particular diets, naturally abundant compounds may have become part of the set of environmental co-determinants that shaped brain structure and function. Here we investigated whether bioactive factors found in apples directly affect hippocampal neural stem cells and promote neurogenesis in the adult mouse. Whereas the consumption of apple juice per se neither altered adult hippocampal neurogenesis nor improved learning and memory, we did find specific direct effects of apple-derived factors on neural stem cell survival and differentiation. Our results revealed that quercetin, the most abundant flavanol in apple peel, was anti-proliferative at high concentrations but acted pro-neurogenically at low concentrations. This was confirmed in vivo, with intraperitoneally-delivered quercetin promoting survival and neuronal differentiation, without affecting proliferation, likely via the PI3 kinase-Akt and Nrf2-Keap1 pathways, respectively. Using a bio-assay-guided fractionation approach with high-resolution collision induced dissociation mass spectroscopy, we also identified additional pro-neurogenic compounds in apple flesh that were not related to flavonoids. In particular, we found that 3,5-dihydroxybenzoic acid, a weak agonist to the lactate receptor, significantly increased both in vitro and in vivo neural precursor cell proliferation and neurogenesis. Altogether, this work shows that both flavonoids and 3,5-dihydroxybenzoic acid are pro-neurogenic, not only by activating precursor cell proliferation but also through promoting cell cycle exit, cellular survival, and neuronal differentiation.

neuroscience↗