Browsing by Author "Rodgers, Shaefali P."
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Item Influence of Sex and Stress on Perineuronal Nets in the Prefrontal Cortex(2020-09-29) Khan, Ali Raza; Perez, Emma C.; Siddiqui, RaimaThe effects of exercise have been known to provide significant changes in the brain, as determined from physiological evidence of neurogenesis, vascularization, dendritic complexity and more. When juxtaposed with sedentary subjects, these changes are proved to be beneficial as the experiments in human and animal models reveal enhanced cognition and stress resilience. Recently, certain structures in the brain have been under the spotlight. Amongst the convoluted wiring of the brain are proteins in the extracellular matrix that have a role in neuroplasticity, which is the ability for the brain to heal and rearrange certain connections in response to the environment. These protein structures, perineuronal nets (PNNs), have also been discovered to play a critical role in development. They are therefore acknowledged as unique and significant in relation to physiology and pathology. Here, we focus on tissues from the sedentary subjects that went through developmental exercise in a prior experiment, measuring the quantity of PNNs and recognizing the pattern between sexes and chronic restraint stress (CRS).Item Neural Effects of Weekly Binge Alcohol: Sex Differences?(2019-12) West, Rebecca; Leasure, J. Leigh; Kosten, Therese A.; Rodgers, Shaefali P.; Nixon, KimberlyIn the U.S., 1/6 of adults report binge drinking about 4 times a month. There is also mounting evidence indicating that females may be more vulnerable to the neurotoxic effects of ethanol than males. Using a novel model of weekly binge ethanol exposure, we hypothesized that cellular damage would be greater and detectable earlier in female rats in comparison to male rats. Adult Long-Evans rats were administered 5g/kg ethanol (or an iso-caloric control dose) via intra-gastric gavage once-weekly. Neither BEC (177 mg/dl) nor behavioral intoxication measures differed over time, indicating that tolerance did not occur. Male rats, however, acted more behaviorally intoxicated than females. Brains were collected either 4 or 6 days following the final ethanol dose, and immunohistochemically processed for mature neurons (NeuN), microglia (Iba1), neurogenesis (DCX) and cellular activation (c-Fos). Stereology was used to quantify target cell populations in the hippocampus and medial prefrontal cortex (mPFC). We showed that binge ethanol administration for 11 weeks increases partial activation of microglia in the hippocampus and causes significant dentate gyrus (DG) cell loss despite an increase in neurogenesis in female rats. After 3 and 8 weeks, binge ethanol significantly decreased the number of NeuN+ cells in the DG of male and female rats in comparison to controls. 8 weeks of binge ethanol significantly increased the total number of microglia (Iba1) and the number of partially activated microglia in the hippocampus and mPFC in males and females. Despite no noted behavioral deficits during reversal learning, binged rats had increased cellular activation in the mPFC during testing, indicating decreased neural efficiency. Additionally, 8 weeks of ethanol influenced ultrasonic vocalizations in male rats, however had no effect on female rats. Overall, these results show hippocampal cell loss and an increased inflammatory response in ethanol-vulnerable regions following repeated binge exposures in both male and female rats and showed changes in affect in male rats during behavioral testing.Item Neurogenesis, exercise, and cognitive late effects of pediatric radiotherapy(Neural Plasticity, 2013-04) Rodgers, Shaefali P.; Trevino, Melissa; Zawaski, Janice A.; Gaber, M. Waleed; Leasure, J. LeighBrain cancer is a common type of childhood malignancy, and radiotherapy (RT) is a mainstay of treatment. RT is effective for tumor eradication, and survival rates are high. However, RT damages the brain and disrupts ongoing developmental processes, resulting in debilitating cognitive “late” effects that may take years to fully manifest. These late effects likely derive from a long-term decrement in cell proliferation, combined with a neural environment that is hostile to plasticity, both of which are induced by RT. Long-term suppression of cell proliferation deprives the brain of the raw materials needed for optimum cognitive performance (such as new neurons in the hippocampus and new glia in frontal cortex), while chronic inflammation and dearth of trophic substances (such as growth hormone) limit neuroplastic potential in existing circuitry. Potential treatments for cognitive late effects should address both of these conditions. Exercise represents one such potential treatment, since it has the capacity to enhance cell proliferation, as well as to promote a neural milieu permissive for plasticity. Here, we review the evidence that cognitive late effects can be traced to RT-induced suppression of cell proliferation and hostile environmental conditions, as well as emerging evidence that exercise may be effective as an independent or adjuvant therapy.Item Radiation-induced growth retardation and microstructural and metabolite abnormalities in the hippcampus(Neural Plasticity, 2016-05) Rodgers, Shaefali P.; Zawaski, Janice A.; Sahnoune, Iman; Leasure, J. Leigh; Gaber, M. WaleedCranial radiotherapy (CRT) increases survival in pediatric brain-tumor patients but can cause deleterious effects. This study evaluates the acute and long-term impact of CRT delivered during childhood/adolescence on the brain and body using a rodent model. Rats received CRT, either 4 Gy fractions × 5 d (fractionated) or a cumulative dose of 20 Gy (single dose) at 28 d of age. Animals were euthanized 1 d, 5 d, or 3.5 mo after CRT. The 3.5 mo group was imaged prior to euthanasia. At 3.5 mo, we observed significant growth retardation in irradiated animals, versus controls, and the effects of single dose on brain and body weights were more severe than fractionated. Acutely single dose significantly reduced body weight but increased brain weight, whereas fractionation significantly reduced brain but not body weights, versus controls. CRT suppressed cell proliferation in the hippocampal subgranular zone acutely. Fractional anisotropy (FA) in the fimbria was significantly lower in the single dose versus controls. Hippocampal metabolite levels were significantly altered in the single dose animals, reflecting a heightened state of inflammation that was absent in the fractionated. Our findings indicate that despite the differences in severity between the doses they both demonstrated an effect on cell proliferation and growth retardation, important factors in pediatric CRT.Item Sex Differences in Cognitive Task Performance and Dendritic Arborization(2022-05-20) Bravo, Diana Renee; Leasure, J. Leigh; Rodgers, Shaefali P.; Spinetta, MichaelDendrites are branched neuronal structures that play a key role in communication via signal integration. Complex dendrites are believed to affect signal transmission where complexity and more dendritic spines are perceived to have more surface area for signal inputs, causing better communication within the brain. Therefore, it is important to explore if dendritic complexity is linked to sex differences in behavioral task performance. The current study placed 14 male and 14 female adult rats in the 5-Choice Serial Reaction Time Task (5CSRTT) for a total of 9 weeks. This cognitive-based task gets increasingly difficult as the rats progress to a new stage. Results from this showcased a sex difference in performance, where males outperformed females on various outcome measures. From this, a learning index (LI) was developed to assign each animal a score for overall performance. Males had higher overall LIs. It is unknown whether a relationship between sex-dependent 5CSRTT performance and dendritic morphology and spines exists. Thus, it was hypothesized that males would have greater arborization (dendritic length and number of bifurcations) and spine count and density in the anterior cingulate (ACC), infralimbic (IL), and prelimbic (PRL) cortices of the medial prefrontal cortex (mPFC). Apical and basilar dendrites of layer II/III pyramidal neurons of the mPFC were imaged. No sex differences were observed nor were there any significant relationships between the LI and any of the outcome measures. However, apical dendrites had significantly higher spine densities versus basilar dendrites in the ACC and IL, indicating that there are more predicted spines on apical dendrites than basilar dendrites. While a sex difference was not observed, given that apical dendrite’s functionality is to communicate to cortical and global subcortical regions, suggests that remote regions are involved and should be explored. Overall, sex difference in performance was not associated with a sex difference in dendritic morphology and spines.