Biology subjects

Dannenhoffer, C. A.

Publications and source records attributed to Dannenhoffer, C. A..

3 recordsLinked to original sources

bioRxiv2022

Impact of adolescent intermittent ethanol exposure on interneurons and their surrounding perineuronal nets in adulthood.

BackgroundBinge alcohol exposure during adolescence results in long-lasting alterations in brain and behavior. For example, adolescent intermittent ethanol (AIE) exposure in rodents results in long-term loss of functional connectivity among prefrontal cortex (PFC) and striatal regions as well as a variety of neurochemical, molecular, and epigenetic alterations. Interneurons in the PFC and striatum play critical roles in behavioral flexibility and functional connectivity. For example, parvalbumin (PV) interneurons are known to contribute to neural synchrony, and cholinergic interneurons contribute to strategy selection. Furthermore, extracellular perineuronal nets (PNNs) surround some interneurons, particularly PV+ interneurons, to further regulate cellular plasticity. The effect of AIE exposure on expression of these markers within the PFC is not well understood. MethodsThe present study tested the hypothesis that AIE exposure reduces expression of PV+ and ChAT+ interneurons in the adult PFC and striatum and increases related expression of PNNs (marked by binding of Wisteria Floribunda agglutinin lectin; WFA) in adulthood. Male rats were exposed to AIE (5 g/kg/day, 2-days-on/2-days-off, i.g., P25-P54) or water (CON), and brain tissue was harvested in adulthood (> P80). Immunohistochemistry and co-immunofluorescence were used to assess expression of ChAT, PV, and WFA labeling within the adult PFC and striatum following AIE exposure. ResultsChAT and PV interneuron numbers in the striatum and PFC were unchanged after AIE exposure. However, WFA labeling in the PFC of AIE-exposed rats was increased compared to CON rats. Moreover, significantly more PV neurons were surrounded by WFA labeling in AIE-exposed subjects relative to controls in both PFC subregions assessed: the orbitofrontal cortex (CON = 34%; AIE = 40%) and the medial PFC (CON = 10%; AIE = 14%). ConclusionsThese findings indicate that while PV interneuron expression in the adult PFC and striatum is unaltered following AIE exposure, PNNs surrounding these neurons (indicated by extracellular WFA binding) are increased. This increase in PNNs may restrict plasticity of the ensheathed neurons, thus contributing to impaired microcircuitry in frontostriatal connectivity and related behavioral impairments.

neuroscience↗

bioRxiv2021

Altered cortico-subcortical network after adolescent alcohol exposure mediates behavioral deficits in flexible decision-making

Behavioral flexibility, the ability to modify behavior according to changing conditions, is essential to optimize decision-making. Deficits in behavioral flexibility that persist into adulthood are one consequence of adolescent alcohol exposure, and another is decreased functional connectivity in brain structures involved in decision-making; however, a link between these two outcomes has not been established. We assessed effects of adolescent alcohol and sex on both Pavlovian and instrumental behaviors and functional connectivity in adult animals to determine associations between behavioral flexibility and resting-state functional connectivity. Alcohol exposure impaired attentional set reversals and decreased functional connectivity among cortical and subcortical regions-of-interest that underlie flexible behavior. Moreover, mediation analyses indicated that adolescent alcohol-induced reductions in functional connectivity within a subnetwork of affected brain regions mediated errors committed during reversal learning. These results provide a novel link between persistent reductions in brain functional connectivity and deficits in behavioral flexibility resulting from adolescent alcohol exposure.

neuroscience↗

bioRxiv2019

Critical Variables to be Considered when Attempting to Estimate Blood Ethanol Concentrations in Rats from g/kg Exposure Data

BackgroundIn rodent studies of ethanol (EtOH) consumption where blood sample collection does not occur, there is often mention of likely BECs based on prior studies. These studies may vary in dose(s) used, age/sex/species, or administration route. Often, intake studies may presume that binge-levels were achieved without knowing that BECs exceeded 80 mg% (binge threshold). In human studies, estimated BECs (eBECs) have been derived using complex formulas that consider EtOH consumption level and the weight and sex of the individual.\n\nMethodThree datasets were used to derive eBECs using a conversion factor (CF) that considers gram (g) of EtOH per kilogram (kg) of animal weight and other variables that may influence BECs such as age, sex, dose, route, vehicle, chronicity, and timing post-exposure. Regression analyses were also conducted for each dataset, building regression models with BEC as the response and other variables in the study specific to each dataset as predictor variables.\n\nResultsDataset1 assessed age, sex and post-injection time point. Both CF and regression analyses determined that different CFs should be used for 10- and 30-min post-administration time points. Dataset2 assessed age, dose, vehicle and post-intubation time point. Depending on the post-intubation time point, several CFs were used to derive eBECs. When weight was not used as a regression variable, data across approaches corresponded, with age differences emerging later in elimination phase. In Dataset3 that used BECs from a repeated intake study, chronic exposure influenced CFs, although regression analysis did not yield similar findings.\n\nConclusionsAlthough eBECs can be derived, critical variables vary with subject and test conditions and do not always concur with results of regression analyses. Although, not designed to replace assessment of BECs when sample collection is possible, the CF approach may prove useful when estimating BECs in studies where assessments are not feasible.

neuroscience↗