Biology subjects

Schulz, K. M.

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

4 recordsLinked to original sources

bioRxiv2025

The effects of adolescent stress on adult social behavior and basolateral amygdala GABAergic neurons with perineuronal nets depend on prenatal stress history

Developmental stress is a well-established risk factor for mental health disorders, yet the neural mechanisms underlying these outcomes remain incompletely understood. Inhibitory brain networks, particularly within the amygdala, are disrupted by stress and implicated in stress-related psychopathologies. Using a rodent model, the current study investigated the isolated and combined effects of prenatal and adolescent stress on adult social interactions and GABAergic neurons surrounded by perineuronal nets (PNNs) in the basolateral amygdala (BLA). Male and female rats were exposed to chronic variable stressors (CVS) prenatally (PS), during adolescence (AS), or during both prenatal and adolescent periods (PS+AS). In adulthood, all animals were tested for social behavior with same-sex weight-matched partners, and brains were collected for identification of BLA inhibitory neurons (GAD67 staining) and PNNs (Wisteria Floribunda Agglutinin staining). For social behavior, AS alone robustly increased social investigation in adulthood relative to non-stressed (NS) controls and animals exposed to combined PS+AS. PS+AS subjects did not significantly differ from NS controls, suggesting that prenatal stress exposure prevented adolescent stress-induced increases in adult social investigation. An analogous data pattern was observed in the BLA. AS alone decreased the number GAD67+ neurons surrounded by PNNs (co-labeled) relative to NS controls and subjects exposed to combined PS+AS. When the percentage of total GAD67+ neurons co-labeled with PNNs was assessed, both PS alone and AS alone reduced the proportion of GAD67+ neurons surrounded by PNNs, whereas combined PS+AS had no effect. Overall, these data suggest that prenatal stress exposure prevents adolescent stress-induced disruptions to perineuronal nets surrounding inhibitory neurons in the BLA, potentially conferring resilience to adolescent stress-induced changes in inhibitory function and social behavior. HighlightsO_LIAdolescent stress exposure increased social investigation in adulthood. C_LIO_LIAdolescent stress decreased the number of BLA cells co-labeled with GAD67 and WFA. C_LIO_LIPrenatal or adolescent stress decreased the proportion of inhibitory neurons with PNNs. C_LIO_LIWhen preceded by prenatal stress, effects of adolescent stress were not observed. C_LI

neuroscience↗

bioRxiv2025

Vascular Biomechanics and Brain Biochemistry in Aged and Alzheimer's Disease Mouse Models

Age-related vascular changes accompany or precede the development of Alzheimers disease (AD) pathology. The comorbidity of AD and arterial stiffening may suggest that vascular changes have a pathogenic role. Carotid artery mechanics and hemodynamics have been associated with age-related cognitive decline. However, the impact of hemodynamics and vascular mechanics on regional vulnerability within the brain have not been thoroughly explored. Despite the venous systems role in transport, the impact of age-related alterations of the brain venous circulation on cognitive impairment is much less understood compared to the arterial system. By studying vascular mechanics and the resulting spatially-resolved brain lipids in young and aged AD mice, we can determine the relationship between vascular stiffening and brain function. Young and aged female 3xTg mice and age-matched controls were imaged using a combination of ultrasound and mass spectrometry. Wall shear stress varied across age and AD (p<0.05). The circumferential cyclic strain values for the carotid arteries and the WSS values for the jugular veins between groups were measured but were not statistically significant. Both mean velocity and pulsatility index (PI) varied across age and AD (p<0.05). Liquid chromatography mass spectrometry (LC-MS) of brain tissue identified several lipids and metabolites with statistically significant quantities (p<0.05). The fold change was computed for young AD vs. young control, aged AD vs. aged control, aged control vs. young control, and aged AD vs. young AD. The abundance of several lipid headgroups changed significantly with respect to age and AD. Phosphatidylcholines (PC), phosphatidylethanolamines (PE), cardiolipins (CL), phosphatidylserines (PS), and lysophosphatidylcholines (LPC) have been shown to decrease with AD in previous studies. However, we observed a statistically significant increase in PC, PE, CL, PS, and LPC in the aged 3xTG mouse model compared to aged controls. Hexosylceramides (HexCer), ceramides (CER) and sphingomyelin (SM), classes of sphingolipids; lysophosphatidylethanolamine (LPE), a class of phospholipids; and onogalactosyl diglycerides (MGDG), a class of glycerolipids, have been shown to increase with AD in previous studies which aligns with the statistically significant increase of LPC, HexCer, CER, SM, LPE, and MDG observed in the aged 3xTg group compared to controls in this work. Combining both ultrasound imaging and mass spectrometry, we were able determine significant differences in the vascular biomechanics and brain biochemistry seen with aging and AD.

neuroscience↗

bioRxiv2025

Testosterone differentially modulates the display of agonistic behavior and dominance over opponents before and after adolescence in male Syrian hamsters

The current study investigated the influence of testosterone on agonistic behavior and dominance over an opponent before and after adolescence in male Syrian hamsters (Mesocricetus auratus). We hypothesized that testosterone-dependent modulation of agonistic behavior would be greater following adolescent development. To test this hypothesis, prepubertal (14 days of age) and adult subjects (52-62 days of age) were gonadectomized and immediately implanted with testosterone or vehicle pellets. Fourteen days later, agonistic behavior was assessed in a neutral arena with age-matched testosterone-treated opponents. Flank marking was also assessed separately in response to male odors alone. Our hypothesis predicted that testosterone would modulate agonistic behavior and dominance over an opponent in adult but not in prepubertal subjects, however, only flank marking behavior followed the predicted data pattern. During both social interaction and scent tests, testosterone increased flank marking behavior in adults, but failed to increase flank marking in prepubertal subjects. Contrary to our predictions, testosterone treatment increased prepubertal subject attacks, decreased submissive tail-up displays, and facilitated prepubertal subject dominance over opponents. In adults, testosterone increased paws-on investigation and flank marking during social interactions. Taken together, these data indicate that some, but not all aspects of agonistic behavior are sensitive to the activational effects of testosterone prior to adolescence, and that activational effects of testosterone differ substantially between prepubertal and adult males. Our results may have implications for early pubertal timing and increased risk for externalizing symptoms and aggressive behavior in humans. HighlightsO_LITestosterone increased attacks and decreased submissive displays in prepubertal males C_LIO_LITestosterone increased dominance over opponents in prepubertal males C_LIO_LIPrepubertal males displayed more attacks and submissive behaviors than adults overall C_LIO_LITestosterone increased flank marking behavior only in adult males C_LI

neuroscience↗

bioRxiv2024

Adolescent development of anxiety-related behavior and shifts in behavioral responsiveness to estradiol in female mice

Early pubertal onset during adolescence is consistently linked with increased risk of anxiety and depression in girls. Although estradiol tends to have anxiolytic effects in adulthood, whether sensitivity to estradiols anxiolytic actions increases during adolescence is not clear. Using a rodent model, the current study tested the hypothesis that a shift in sensitivity to the anxiolytic effects of estradiol occurs during adolescence. To test this hypothesis, prepubertal and adult C57BL/6 female mice were ovariectomized, implanted with vehicle- or estradiol-filled silastic capsules, and behavioral tested one week later in the open field and elevated zero maze. Our hypothesis predicted that estradiol would decrease anxiety-related behavior to a greater extent in adults than in adolescent females, however, our results did not support this hypothesis. In the open field, estradiol implants significantly decreased anxiety-like behavior in adolescent females (relative to vehicle) and had little to no effect on the behavior of adults. These data suggest that adolescence is associated with a downward shift in sensitivity to the anxiolytic effects of estradiol on behavior in the open field. In contrast, although estradiol treatment did not influence anxiety-like responses in the elevated zero maze in early adolescent or adult females, adolescent females displayed significantly higher levels of anxiety-like behavior than adults. These findings demonstrate that substantial changes in anxiety-related behavior occur during adolescence, including a context-dependent shift in behavioral responsiveness to estradiol.

neuroscience↗