Sex differences exist in the regulation of adult neurogenesis in the hippocampus in response to hormones and cognitive training. Here we investigated the trajectory and maturation rate of adult-born neurons in the dentate gyrus (DG) of male and female rats. Sprague-Dawley rats were perfused two hours, 24 hours, one, two or three weeks after BrdU injection, a DNA synthesis marker that labels dividing progenitor cells and their progeny. Adult-born neurons (BrdU/NeuN-ir) matured faster in males compared to females. Males had a greater density of neural stem cells (Sox2-ir) in the dorsal, but not in the ventral, DG and had higher levels of cell proliferation (Ki67-ir) than non-proestrous females. However, males showed a greater reduction in neurogenesis between one and two weeks after mitosis, whereas females showed similar levels of neurogenesis throughout the weeks. The faster maturation and greater attrition of new neurons in males compared to females suggests greater potential for neurogenesis to respond to external stimuli in males and emphasizes the importance of studying sex on adult hippocampal neurogenesis. Significance Statement Previously studies examining the characteristics of adult-born neurons in the dentate gyrus have used almost exclusively male subjects. Researchers have assumed the two sexes have a similar maturation and attrition of new neurons in the dentate gyrus of adults. However, this study highlights notable sex differences in the attrition, maturation rate and potential of neurogenesis in the adult hippocampus that has significant implications for the field of neuroplasticity. These findings are important in understanding the relevance of sex differences in the regulation of neurogenesis in the hippocampus in response to stimuli or experience and may have consequences for our understanding of diseases that involve neurodegeneration of the hippocampus, particularly those that involve sex differences, such as Alzheimer's disease and depression.

After a successful launch, the James Webb Space Telescope is preparing to undertake one of its principal mission objectives, the characterization of the atmospheres of exoplanets. The Single Object Slitless Spectroscopy (SOSS) mode of the Near Infrared Imager and Slitless Spectrograph (NIRISS) is the only observing mode that has been specifically designed for this objective. It features a wide simultaneous spectral range (0.6–2.8 μm) through two spectral diffraction orders. However, due to mechanical constraints, these two orders overlap slightly over a short range, potentially introducing a “contamination” signal in the extracted spectrum. We show that for a typical box extraction, this contaminating signal amounts to 1% or less over the 1.6–2.8 μm range (order 1), and up to 1% over the 0.85–0.95 μm range (order 2). For observations of exoplanet atmospheres (transits, eclipses or phase curves) where only temporal variations in flux matter, the contamination signal typically biases the results by order of 1% of the planetary atmosphere spectral features strength. To address this problem, we developed the Algorithm to Treat Order ContAmination (ATOCA). By constructing a linear model of each pixel on the detector, treating the underlying incident spectrum as a free variable, ATOCA is able to perform a simultaneous extraction of both orders. We show that, given appropriate estimates of the spatial trace profiles, the throughputs, the wavelength solutions, as well as the spectral resolution kernels for each order, it is possible to obtain an extracted spectrum accurate to within 10 ppm over the full spectral range.

oxytocin in PBS indicating that the nanoparticle may be used as an alternative brain delivery 37 system. We showed that oxytocin has sex-specific effects on social investigation, body mass, 38 sedation, and the oxytocin system. In contrast, similar effects were observed in both sexes in 39 neurogenesis and plasma 17β-estradiol. Our work suggests that sex differences in oxytocin 40 regulation of brain endpoints is region-specific (hypothalamus versus hippocampus) and that 41 oxytocin does not promote social investigation in females. 42 large molecules through the adsorptive-mediated transcytosis mechanism (Lu, 2012; Ovensa 89 Inc., 2018). Therefore, in the present study we compared the effects of systemic oxytocin with 90 and without the nanoparticle TRIOZAN TM . 91The objective of this study was to investigate whether systemic oxytocin delivered in 92 vehicle or with a nanoparticle drug delivery platform (TRIOZAN TM ) regulates social 93 investigation, oxytocin levels in the brain and periphery, oxytocin-immunoreactive cells in the 94 hypothalamus (SON and PVN) and adult hippocampal neurogenesis in male and female rats. We 95 hypothesized that oxytocin would impact the sexes differentially and that TRIOZAN TM would 96 increase delivery of oxytocin to the brain and result in enhanced effects on social investigation 97 and hippocampal neurogenesis. 98 99 Materials and Methods 100 Animals and treatments 101Adult male and female Sprague-Dawley rats (n=5-8/treatment/sex; 60 days old and 102 tested around 80 days old) were obtained from Charles River (Quebec, Canada) and double-103 housed with food and water available ad libitum. All protocols were approved by the 104 Institutional Animal Care Committee at the University of British Columbia and conformed to the 105 guidelines set out by the Canadian Council for Animal Care. Ten days after arrival, males and 106 females were randomly divided into one of the following treatment groups: oxytocin in 0.1 M 107 PBS (0.5 or 1.0 mg/kg), oxytocin delivered in TRIOZAN TM (0.5 or 1.0 mg/kg, prepared by PO-108

No abstract

Sex differences exist in the regulation of adult neurogenesis in the hippocampus in response to hormones and cognitive training. Here we investigated the trajectory and maturation rate of adult-born neurons in the dentate gyrus (DG) of male and female rats. Sprague-Dawley rats were perfused one, two or three weeks after BrdU injection, marking newly dividing cells.Adult-born neurons (BrdU/NeuN-ir) matured faster in males compared to females. Males had a greater density of neural stem cells (Sox2-ir) in the dorsal, but not in the ventral, DG and had higher levels of cell proliferation (Ki67-ir) than females. Males had a greater reduction in neurogenesis between one and two weeks after mitosis, while females showed similar levels of neurogenesis throughout. The faster maturation and attrition of new neurons suggests greater potential for neurogenesis to respond to external stimuli in males compared to females and emphasizes the importance of studying sex on adult hippocampal neurogenesis.(Fisher Scientific) solution for cryoprotection and remained in the solution until sectioning. Brains were sliced into 30 μ m coronal sections using a Leica SM2000R microtome (Richmond Hill, Ontario, Canada). Sections were collected in series of ten throughout the entire rostral-caudal extent of the hippocampus and stored in anti-freeze solution consisting of ethylene glycol, glycerol and 0.1M PBS at -20°C until immunostaining. Complete series of sections were immunohistochemically stained for BrdU/DCX and BrdU/NeuN to examine sex differences in the maturation timeline of new neurons, for Sox2 to examine the number of neural stem cells, and for Ki67 to examine actively dividing progenitor cells. In addition, the brain sections were double-stained for BrdU/Sox2 to examine changes of Sox2 expression over the three weeks after BrdU injection. Radioimmunoassay for 17β-estradiol and testosteronePrevious studies reported that 17β-estradiol increases cell proliferation in females but not males (Tanapat et al., 1999;Barker and Galea, 2008) and androgens can influence survival of new neurons in males but not females (Spritzer and Galea, 2007;Duarte-Guterman et al., 2019).Thus, we examined serum levels of 17β-estradiol and testosterone in females and males, respectively.Blood samples were stored at 4℃ overnight and centrifuged at 10g for 15 minutes to collect serum.Serum 17β-estradiol levels in female rats and serum testosterone levels in male rats were assayed using commercially available radioimmunoassay (RIA) kits from Beckman Coulter (Brea, USA) or MP Biomedicals (Santa Ana, USA) respectively. The sensitivity of the RIA kits was 0.75 ng/mL for 17β-estradiol and 0.03ng/mL for testosterone. The intra-and inter-assay coefficient of variation were <8.9% and <12.2% respectively for 17β-estradiol and <8.2% and <13.2% for testosterone.None of the females were in proestrus at the time of sacrifice. 4. Immunohistochemistry 4. 1. BrdU/NeuN, BrdU/DCX or BrdU/Sox2 double-stainingThe exogenous DNA synthesis marker, 5-bromo-2'-deoxyuridine (BrdU) is i...