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1. Increasing Progenitor Cell Proliferation in the Sub-Ventricular Zone: A Therapeutic Treatment for Progressive Multiple Sclerosis?

   https://doi.org/10.2174/1872211314999201117130123  

   Sulehria, Tahir ; Corbett, Adrian M. ; Sharma, Neelima ; Nagarajan, Devipriyanka ; Abushamma, Amani ; Gagle, Samantha ; Johnson, Alee ( January 2021 , Recent Patents on Drug Delivery & Formulation)

   null (Ed.)

   Introduction: The purpose of this study was to determine if pharmacological treatmentcould increase progenitor cell proliferation in the Sub-ventricular Zone of aged rats. Previous workhad shown that increasing progenitor cell proliferation in this region correlated well (R2=0.78; p=0.0007) with functional recovery in a damaged corpus callosum (white matter tract), suggesting thatprogenitor cell proliferation results in oligodendrocytes in this region. Methods: 10 month old male and female Sprague Dawley rats were fed the drugs for 30 days in cookiedough, then immunocytochemistry was performed on coronal brain sections, using Ki67 labeling todetermine progenitor cell proliferation. Results: Female rats showed low endogenous (control) progenitor cell proliferation, significantly differentfrom male rats (P<0.0001), at this age. Ascorbic Acid (20 mg/kg, daily for 30 days) increasedprogenitor cell proliferation overall, but maintained the innate gender difference in stem cell proliferation(P=0.001). Prozac (5 mg/kg, daily for 30 days) increased progenitor cell proliferation for femalesbut decreased stem cell proliferation for males, again showing a gender difference (P<0.0001).Simvastatin (1 mg/kg for 30 days) also increased progenitor cell proliferation in females and decreasedprogenitor cell proliferation in males, leading to a significant gender difference. Discussion: The three drug combinations (fluoxetine, simvastatin, and ascorbic acid, patent #9,254,281) led to ~ 4 fold increase in progenitor cell proliferation in females, while male progenitorcell proliferation was highest with 50 mg/kg ascorbic acid. However, the ascorbic acid increase in proliferationappears to be only on the sides of the ventricles, which is not the region that normally givesrise to oligodendrocytes. Conclusion: There are innate gender differences in progenitor cell proliferation at the Sub-VentricularZone at middle age in rats, possibly due to the loss of estrogen in females. We also see notable genderdifferences in progenitor cell proliferation in the Sub ventricular Zone in response to common drugs,such as fluoxetine, simvastatin and Vitamin C (ascorbic acid). 

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2. Comparison between two- and three-dimensional scoring of zebrafish response to psychoactive drugs: identifying when three-dimensional analysis is needed

   https://doi.org/10.7717/peerj.7893  

   Macrì, Simone ; Clément, Romain J.G. ; Spinello, Chiara ; Porfiri, Maurizio ( January 2019 , PeerJ)

   Zebrafish ( Danio rerio ) have recently emerged as a valuable laboratory species in the field of behavioral pharmacology, where they afford rapid and precise high-throughput drug screening. Although the behavioral repertoire of this species manifests along three-dimensional (3D), most of the efforts in behavioral pharmacology rely on two-dimensional (2D) projections acquired from a single overhead or front camera. We recently showed that, compared to a 3D scoring approach, 2D analyses could lead to inaccurate claims regarding individual and social behavior of drug-free experimental subjects. Here, we examined whether this conclusion extended to the field of behavioral pharmacology by phenotyping adult zebrafish, acutely exposed to citalopram (30, 50, and 100 mg/L) or ethanol (0.25%, 0.50%, and 1.00%), in the novel tank diving test over a 6-min experimental session. We observed that both compounds modulated the time course of general locomotion and anxiety-related profiles, the latter being represented by specific behaviors (erratic movements and freezing) and avoidance of anxiety-eliciting areas of the test tank (top half and distance from the side walls). We observed that 2D projections of 3D trajectories (ground truth data) may introduce a source of unwanted variation in zebrafish behavioral phenotyping. Predictably, both 2D views underestimate absolute levels of general locomotion. Additionally, while data obtained from a camera positioned on top of the experimental tank are similar to those obtained from a 3D reconstruction, 2D front view data yield false negative findings. 

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3. Zebrafish gonad mutant models reveal neuroendocrine mechanisms of brain sexual dimorphism and male mating behaviors of different brain regions

   https://doi.org/10.1186/s13293-023-00534-7  

   Dai, Xiangyan ; Pradhan, Ajay ; Liu, Jiao ; Liu, Ruolan ; Zhai, Gang ; Zhou, Linyan ; Dai, Jiyan ; Shao, Feng ; Yuan, Zhiyong ; Wang, Zhijian ; et al ( August 2023 , Biology of Sex Differences)

   Sexually dimorphic mating behaviors differ between sexes and involve gonadal hormones and possibly sexually dimorphic gene expression in the brain. However, the associations among the brain, gonad, and sexual behavior in teleosts are still unclear. Here, we utilized germ cells-freetdrd12knockout (KO) zebrafish, and steroid synthesis enzymecyp17a1-deficient zebrafish to investigate the differences and interplays in the brain–gonad–behavior axis, and the molecular control of brain dimorphism and male mating behaviors.

   Tdrd12^+/−;cyp17a1^+/−double heterozygous parents were crossed to obtaintdrd12^−/−;cyp17a1^+/+(tdrd12 KO),tdrd12^+/+;cyp17a1^−/−(cyp17a1 KO), andtdrd12^−/−;cyp17a1^−/−(double KO) homozygous progenies. Comparative analysis of mating behaviors were evaluated using Viewpoint zebrafish tracking software and sexual traits were thoroughly characterized based on anatomical and histological experiments in these KOs and wild types. The steroid hormone levels (testosterone, 11-ketotestosterone and 17β-estradiol) in the brains, gonads, and serum were measured using ELISA kits. To achieve a higher resolution view of the differences in region-specific expression patterns of the brain, the brains of these KOs, and control male and female fish were dissected into three regions: the forebrain, midbrain, and hindbrain for transcriptomic analysis.

   Qualitative analysis of mating behaviors demonstrated thattdrd12^−/−fish behaved in the same manner as wild-type males to trigger oviposition behavior, whilecyp17a1^−/−and double knockout (KO) fish did not exhibit these behaviors. Based on the observation of sex characteristics, mating behaviors and hormone levels in these mutants, we found that the maintenance of secondary sex characteristics and male mating behavior did not depend on the presence of germ cells; rather, they depended mainly on the 11-ketotestosterone and testosterone levels secreted into the brain–gonad regulatory axis. RNA-seq analysis of different brain regions revealed that the brain transcript profile oftdrd12^−/−fish was similar to that of wild-type males, especially in the forebrain and midbrain. However, the brain transcript profiles ofcyp17a1^−/−and double KO fish were distinct from those of wild-type males and were partially biased towards the expression pattern of the female brain. Our results revealed important candidate genes and signaling pathways, such as synaptic signaling/neurotransmission, MAPK signaling, and steroid hormone pathways, that shape brain dimorphism and modulate male mating behavior in zebrafish.

   Our results provide comprehensive analyses and new insights regarding the endogenous interactions in the brain–gonad–behavior axis. Moreover, this study revealed the crucial candidate genes and neural signaling pathways of different brain regions that are involved in modulating brain dimorphism and male mating behavior in zebrafish, which would significantly light up the understanding the neuroendocrine and molecular mechanisms modulating brain dimorphism and male mating behavior in zebrafish and other teleost fish.

    

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4. In utero exposure to electronic-cigarette aerosols decreases lung fibrillar collagen content, increases Newtonian resistance and induces sex-specific molecular signatures in neonatal mice

   https://doi.org/10.1007/s43188-021-00103-3  

   Cahill, Kerin M. ; Gartia, Manas R. ; Sahu, Sushant ; Bergeron, Sarah R. ; Heffernan, Linda M. ; Paulsen, Daniel B. ; Penn, Arthur L. ; Noël, Alexandra ( April 2022 , Toxicological Research)

   Abstract Approximately 7% of pregnant women in the United States use electronic-cigarette (e-cig) devices during pregnancy. There is, however, no scientific evidence to support e-cig use as being ‘safe’ during pregnancy. Little is known about the effects of fetal exposures to e-cig aerosols on lung alveologenesis. In the present study, we tested the hypothesis that in utero exposure to e-cig aerosol impairs lung alveologenesis and pulmonary function in neonates. Pregnant BALB/c mice were exposed 2 h a day for 20 consecutive days during gestation to either filtered air or cinnamon-flavored e-cig aerosol (36 mg/mL of nicotine). Lung tissue was collected in offspring during lung alveologenesis on postnatal day (PND) 5 and PND11. Lung function was measured at PND11. Exposure to e-cig aerosol in utero led to a significant decrease in body weights at birth which was sustained through PND5. At PND5, in utero e-cig exposures dysregulated genes related to Wnt signaling and epigenetic modifications in both females (~ 120 genes) and males (40 genes). These alterations were accompanied by reduced lung fibrillar collagen content at PND5—a time point when collagen content is close to its peak to support alveoli formation. In utero exposure to e-cig aerosol also increased the Newtonian resistance of offspring at PND11, suggesting a narrowing of the conducting airways. At PND11, in females, transcriptomic dysregulation associated with epigenetic alterations was sustained (17 genes), while WNT signaling dysregulation was largely resolved (10 genes). In males, at PND11, the expression of only 4 genes associated with epigenetics was dysregulated, while 16 Wnt related-genes were altered. These data demonstrate that in utero exposures to cinnamon-flavored e-cig aerosols alter lung structure and function and induce sex-specific molecular signatures during lung alveologenesis in neonatal mice. This may reflect epigenetic programming affecting lung disease development later in life. 

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5. Scale dependence of sex‐specific movement in a small‐bodied stream fish

   https://doi.org/10.1111/fwb.13309  

   Clark, Scott R. ; Kreiser, Brian R. ; Schaefer, Jacob F. ; Stewart, Laura K. ( May 2019 , Freshwater Biology)

   Animal movement at localised scales is often modulated by competing pressures such as avoiding predators while acquiring resources and mates. The relative magnitude of these trade‐offs may affect males and females differently, often resulting in sex‐specific differences in movement.

   Sex‐biases in movement have been linked to mating systems (e.g. monogamy or polygamy) in birds and mammals; however, this relationship has received less attention among fishes. Using passive integrated transponder tags and a series of stationary antennas, we evaluated the movement dynamics of a small‐bodied, sexually dimorphic stream fishFundulus olivaceusover a 30‐day period in a fourth‐order tributary to the Pascagoula River in Mississippi (U.S.A.).

   We documented dissimilar sex‐specific movement behaviours at different spatial scales that were likely to be facilitated by differential resource demands and competitive pressures. Females exhibited an increased propensity to engage in longer, exploratory moves (>30 m); whereas most males remained active within an established territory, making few long‐distance longitudinal movements.

   Local activity levels (proportion of individuals moving) were positively related to density (manipulated during the study), and density was found to affect the magnitude of sex‐specific movement. In contrast to females, males increased local activity and movement distance at the reduced density, presumably to expand territory size or mate‐searching behaviours, suggesting local mate competition may suppress the movement distance of males.

   Despite some evidence substantiating a relationship between movement and mating system, our results suggest that the documented sex‐specific differences may be related to traits that co‐evolve with mating systems, rather than the mating system per se. Our findings also highlight the importance of spatial scale when evaluating patterns of sex‐biased movement tendencies.

    

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