Biology subjects

Schatschneider, C.

Publications and source records attributed to Schatschneider, C..

3 recordsLinked to original sources

bioRxiv2025

Nicotine in E-Cigarette Aerosol Reduces GABA Neuron Migration via the α7 Nicotinic Acetylcholine Receptor

Prenatal nicotine exposure is linked to adverse neurodevelopmental outcomes, yet e-cigarette use during pregnancy continues to rise due to aggressive marketing efforts and misconceptions of safety. We investigated the effect of prenatal e-cigarette aerosol exposure on the migration of GABA neurons, a developmental process critical for the establishment of cerebral cortical circuitry. Pregnant mice were exposed to nicotine-containing aerosol (e-cigarette), nicotine-free aerosol (e-liquid) or room air (control) daily beginning 2 weeks before conception and continuing until gestational day 14. E-cigarette, but not e-liquid, aerosol significantly reduced GABA neuron density in the dorsal cerebral wall at rostral forebrain level and within the marginal zone, reflecting region-specific vulnerabilities. In vitro explant cultures revealed that nicotine dose-dependently reduced neuronal migration, and this effect was mimicked by a selective 7 nicotinic acetylcholine receptor (nAChR) agonist. Blocking the 7 nAChR using a selective antagonist attenuated the effects of nicotine on neuronal migration. These findings reveal a previously unrecognized vulnerability of GABA neuron migration to e-cigarette aerosol and identify 7 nAChR activation as a mechanism for nicotine-induced impairment of GABA neuron migration. Moreover, the findings highlight the need for translational efforts to update clinical guidance and public policy regarding e-cigarette use during pregnancy.

neuroscience↗

bioRxiv2024

Rescuing impaired hippocampal-cortical interactions and spatial reorientation learning and memory during sleep in a mouse model of Alzheimer's disease using hippocampal 40 Hz stimulation

Summary/AbstractIn preclinical Alzheimers disease (AD), spatial learning and memory is impaired. We reported similar impairments in 3xTg-AD mice on a virtual maze (VM) spatial-reorientation-task that requires using landmarks to navigate. Hippocampal (HPC)-cortical dysfunction during sleep (important for memory consolidation) is a potential mechanism for memory impairments in AD. We previously found deficits in HPC-cortical coordination during sleep coinciding with VM impairments the next day. Some forms of 40 Hz stimulation seem to clear AD pathology in mice, and improve functional connectivity in AD patients. Thus, we implanted a recording array targeting parietal cortex (PC) and HPC to assess HPC-PC coordination, and an optical fiber targeting HPC for 40 Hz or sham optogenetic stimulation in 3xTg/PVcre mice. We assessed PC delta waves (DW) and HPC sharp wave ripples (SWRs). In sham mice, SWR-DW cross-correlations were reduced, similar to 3xTg-AD mice. In 40 Hz mice, this phase-locking was rescued, as was performance on the VM. However, rescued HPC-PC coupling no longer predicted performance as in NonTg animals. Instead, DWs and SWRs independently predicted performance in 40 Hz mice. Thus, 40 Hz stimulation of HPC rescued functional interactions in the HPC-PC network, and rescued impairments in spatial navigation, but did not rescue the correlation between HPC-PC coordination during sleep and learning and memory. Together this pattern of results could inform AD treatment timing by suggesting that despite applying 40 Hz stimulation before significant tau and amyloid aggregation, pathophysiological processes led to brain changes that were not fully reversed even though cognition was recovered. Significance StatementOne of the earliest symptoms of Alzheimers disease (AD) is getting lost in space or experiencing deficits in spatial navigation, which involve navigation computations as well as learning and memory. We investigated cross brain region interactions supporting memory formation as a potential causative factor of impaired spatial learning and memory in AD. To assess this relationship between AD pathophysiology, brain changes, and behavioral alterations, we used a targeted approach for clearing amyloid beta and tau to rescue functional interactions in the brain. This research strongly connects brain activity patterns during sleep to tau and amyloid accumulation, and will aid in understanding the mechanisms underlying cognitive dysfunction in AD. Furthermore, the results offer insight for improving early identification and treatment strategies.

animal behavior and cognition↗

bioRxiv2023

Learning and memory deficits produced by aspartame are heritable via the paternal lineage

Environmental exposures produce heritable traits that can linger in the population for one or two generations. Millions of individuals consume substances such as artificial sweeteners daily that are declared safe by regulatory agencies without evaluation of their potential heritable effects. We show that consumption of aspartame, an FDA-approved artificial sweetener, daily for up to 16-weeks at doses equivalent to only 7-15% of the FDA recommended maximum daily intake value (equivalent to 2-4 small, 8 oz diet soda drinks per day) produces significant spatial learning and memory deficits in mice. Moreover, the cognitive deficits are transmitted to male and female descendants along the paternal lineage suggesting that aspartames adverse cognitive effects are heritable, and that they are more pervasive than current estimates, which consider effects in the directly exposed individuals only. Traditionally, deleterious environmental exposures of pregnant and nursing women are viewed as risk factors for the health of future generations. Environmental exposures of men are not considered to pose similar risks. Our findings suggest that environmental exposures of men can produce adverse impact on mental health of future generations and demonstrate the need for considering heritable effects via the paternal lineage as part of the regulatory evaluations of artificial sweeteners.

neuroscience↗