scholarly journals Androgens enhance adult hippocampal neurogenesis in males but not females in an age-dependent manner

2019 ◽  
Author(s):  
Paula Duarte-Guterman ◽  
Dwayne K. Hamson ◽  
Steven R. Wainwright ◽  
Carmen Chow ◽  
Jessica Chaiton ◽  
...  
Keyword(s):  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Female Rats ◽  
Male Rats ◽  
Dependent Manner ◽  
Middle Aged ◽  
Young Males ◽  
Neuron Survival ◽  
Male And Female Rats ◽  
Age Dependent

AbstractAndrogens (testosterone and dihydrotestosterone) increase adult hippocampal neurogenesis by increasing new neuron survival in male rats and mice via an androgen receptor pathway, but it is not known whether androgens regulate neurogenesis in females and whether the effect is age-dependent. We investigated the effects of dihydrotestosterone, a potent androgen, on neurogenesis in adult and middle-aged males and females. Rats were gonadectomized and injected with the DNA synthesis marker, bromodeoxyuridine (BrdU). The following day rats began receiving daily injections of oil or DHT for 30 days. We evaluated cell proliferation (Ki67) and new neuron survival (BrdU and BrdU/NeuN) in the hippocampus of male and female rats using immunohistochemistry. As expected, DHT increased new neuron survival in young males but surprisingly not in middle-aged male rats. In females, DHT did not significantly affect adult neurogenesis in young or middle age. Our results indicate that DHT regulates adult hippocampal neurogenesis in a sex- and age-dependent manner.

scholarly journals Androgens Enhance Adult Hippocampal Neurogenesis in Males but Not Females in an Age-Dependent Manner

Endocrinology ◽  
2019 ◽  
Vol 160 (9) ◽  
pp. 2128-2136 ◽  
Author(s):  
Paula Duarte-Guterman ◽  
Stephanie E Lieblich ◽  
Steven R Wainwright ◽  
Carmen Chow ◽  
Jessica A Chaiton ◽  
...  
Keyword(s):  
Middle Age ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Female Rats ◽  
Male Rats ◽  
Dependent Manner ◽  
Middle Aged ◽  
Male And Female ◽  
Male And Female Rats ◽  
Age Dependent

Abstract Androgens (testosterone and DHT) increase adult hippocampal neurogenesis by increasing survival of new neurons in male rats and mice via an androgen receptor pathway, but it is not known whether androgens regulate neurogenesis in female rats and whether the effect is age-dependent. We investigated the effects of DHT, a potent androgen, on neurogenesis in young adult and middle-aged male and female rats. Rats were gonadectomized and injected with the DNA synthesis marker bromodeoxyuridine (BrdU). The following day, rats began receiving daily injections of oil or DHT for 30 days. We evaluated cell proliferation (Ki67) and survival of new neurons (BrdU and BrdU/NeuN) in the hippocampus of male and female rats by using immunohistochemistry. As expected, DHT increased the number of BrdU+ cells in young males but surprisingly not in middle-aged males or in young and middle-aged females. In middle age, DHT increased the proportion of BrdU/NeuN cells, an effect driven by females. Androgen receptor expression also increased with aging in both female and male rats, which may contribute to a lack of DHT neurogenic effect in middle age. Our results indicate that DHT regulates adult hippocampal neurogenesis in a sex- and age-dependent manner.

Tyrosine kinase receptor alteration of renal vasoconstriction in rats is sex- and age-related

2012 ◽  
Vol 90 (10) ◽  
pp. 1372-1379 ◽  
Author(s):  
John C. Passmore ◽  
John T. Fleming ◽  
Suresh C. Tyagi ◽  
Jeff C. Falcone
Keyword(s):  
Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Young Male ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
Tyrosine Kinase Receptor ◽  
Middle Aged ◽  
Male And Female Rats ◽  
Age Related

Male rat renal blood vessels undergo reduced contraction to norepinephrine with aging. There is a greater renal vascular impairment in male compared with female rats. We investigated specific tyrosine kinase receptor inhibition of renal interlobar artery responsiveness to phenylephrine in male and female rats at specifically designated ages. Vessels from young male rats contracted much less to phenylephrine when the vessels were pretreated with the tyrosine kinase inhibitors Lavendustin A, HNMPA-(AM)3, or AG1478. Vessels from adult female rats pretreated with Lavendustin A showed no difference in contraction from control, but did demonstrate a slightly reduced contraction when pretreated with AG1478. Middle-aged male rat vessels treated with Lavendustin A demonstrated no inhibition, but the insulin and epidermal growth factor receptor (EGFR) antagonists both induced a decline in contraction. Vessels from aged male rats demonstrated no effect related to the 3 pretreatments. Middle-aged and aged female rats pretreated with any inhibitor demonstrated no inhibitor-dependent alterations. We conclude that maximum contraction of interlobar arteries from adult male rats is reduced when tyrosine kinase receptor activity is reduced. Female rats demonstrated much less inhibitor-related change of contraction.

scholarly journals The aPKC-CBP Pathway Regulates Adult Hippocampal Neurogenesis in an Age-Dependent Manner

2016 ◽  
Vol 7 (4) ◽  
pp. 719-734 ◽  
Author(s):  
Ayden Gouveia ◽  
Karolynn Hsu ◽  
Yosuke Niibori ◽  
Matthew Seegobin ◽  
Gonzalo I. Cancino ◽  
...  
Keyword(s):  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Dependent Manner ◽  
Age Dependent

scholarly journals Sex Differences in Maturation and Attrition of Adult Neurogenesis in the Hippocampus

2019 ◽  
Author(s):  
Shunya Yagi ◽  
Jared E.J. Splinter ◽  
Daria Tai ◽  
Sarah Wong ◽  
Yanhua Wen ◽  
...  
Keyword(s):  
Sex Differences ◽  
Dentate Gyrus ◽  
Adult Neurogenesis ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Female Rats ◽  
Sprague Dawley ◽  
Male And Female Rats ◽  
Maturation Rate ◽  
Adult Born Neurons

ABSTRACTSex 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 StatementPreviously 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.

Age- and sex-dependent stimulation of growth rate in rats by the adrenal inhibitor trilostane

1987 ◽  
Vol 113 (3) ◽  
pp. 479-484 ◽  
Author(s):  
M. N. Sillence ◽  
R. G. Rodway
Keyword(s):  
Growth Rate ◽  
Food Intake ◽  
Conversion Efficiency ◽  
Plasma Corticosterone ◽  
Female Rats ◽  
Male Rats ◽  
Dependent Manner ◽  
Food Conversion ◽  
Male And Female Rats ◽  
Food Conversion Efficiency

ABSTRACT The effects of the adrenal inhibitor trilostane were examined in male and female rats to determine whether growth rate could be improved by lowering circulating plasma corticosterone concentrations. Dose–response studies revealed that in young female rats (125 g) trilostane lowered peak plasma corticosterone levels in a dose-dependent manner. In male rats plasma corticosterone concentrations were reduced only by very high doses of trilostane (200 mg/kg), while lower doses (2–8 mg/kg) actually increased them. Five growth studies were conducted using a total of 90 rats. In female animals, daily injections of trilostane (10 mg/day) caused an age-dependent increase in growth rate ranging from 11% in 127 g rats to 30% in 164 g rats. In three out of four experiments using females, food intake was slightly increased by the drug. Food conversion efficiency was improved consistently by trilostane by up to 18%. Trilostane-treated females had significantly heavier adrenal glands and livers, but lighter kidneys than control rats. When a complete carcass analysis was performed on one experimental group, no significant differences were found. Carcass component weights relative to control values were: body weight (103%), body water (105%), fat-free solids (103%), carcass weight (103%), body length (103%), body fat (95%) and gut content (96%). In male rats (160 g), daily injections of trilostane (10 mg) resulted in a steady and sustained depression of growth rate reflecting a similar fall in food intake, with no change in food conversion efficiency. It is concluded that in older female rats growth rate is constrained by physiological concentrations of glucocorticoids. Younger females are either less sensitive to trilostane or to changes in plasma corticosterone levels. Male rats are less responsive to adrenal suppression by trilostane than are females of a similar age and do not exhibit an anabolic response to this drug. J. Endocr. (1987) 113, 479–484

scholarly journals The Poststroke Peripheral Immune Response Is Differentially Regulated by Leukemia Inhibitory Factor in Aged Male and Female Rodents

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Stephanie M. Davis ◽  
Lisa A. Collier ◽  
Sarah J. Messmer ◽  
Keith R. Pennypacker
Keyword(s):  
Leukemia Inhibitory Factor ◽  
Inhibitory Factor ◽  
Female Rats ◽  
Male Rats ◽  
Spleen Weight ◽  
Dependent Manner ◽  
Spleen Tissue ◽  
Male And Female ◽  
Male And Female Rats ◽  
Significant Difference

Background. The goal of this study was to determine whether leukemia inhibitory factor (LIF) promotes anti-inflammatory activity after stroke in a sex-dependent manner. Methods. Aged (18-month-old) Sprague-Dawley rats of both sexes underwent sham surgery or permanent middle cerebral artery occlusion (MCAO). Animals received three doses of intravenous LIF (125 μg/kg) or PBS at 6, 24, and 48 h before euthanization at 72 h. Spleen weights were measured immediately following euthanization. Western blot was used to measure protein levels of CCL8, CD11b, CXCL9, CXCL10, IL-12 p40, IL-3, and the LIF receptor (LIFR) in spleen tissue. ELISA was used to measure IL-1β, IL-6, TNFα, and IFNγ in spleen tissue. A Griess Assay was used to indirectly quantify NO levels via measurement of nitrite. Levels of cellular markers and inflammatory mediators were normalized to the baseline (sham) group from each sex. Statistical analysis was performed using two-way ANOVA and followed by Fisher’s LSD post hoc test. Results. Aged female rats showed a significantly lower spleen weight after MCAO, but showed a significant increase in spleen size after LIF treatment. This effect was observed in aged male rats, but not to as great of an extent. CD11b levels were significantly higher in the spleens of MCAO+PBS males compared to their female counterparts, but there was no significant difference in CD11b levels between MCAO+LIF males and females. LIF significantly increased CXCL9 after LIF treatment in aged male and female rats. LIFR and IL-3 were upregulated after LIF treatment in aged females. Splenic nitrate increased after MCAO but decreased after LIF treatment in aged females. Splenic nitrate levels did not increase after MCAO but did increase after LIF treatment in aged males. The following cytokines/chemokines were not altered by sex or treatment: TNFα, IL-6, IL-12 p40, CCL8, IFNγ, and CXCL10. Conclusions. LIF treatment after permanent MCAO induces sex-dependent effects on the poststroke splenic response and the production of proinflammatory cytokines among aged rats.

Roles of Up-Regulated Expression of ASIC3 in Sex Difference of Acid-Induced Duodenal HCO3 - Responses

2020 ◽  
Vol 26 (25) ◽  
pp. 3001-3009 ◽  
Author(s):  
Koji Takeuchi ◽  
Yumi Ohashi ◽  
Kikuko Amagase
Keyword(s):  
Sex Difference ◽  
Repeated Administration ◽  
Female Rats ◽  
Male Rats ◽  
Tamoxifen Treatment ◽  
Dependent Manner ◽  
Protective Mechanisms ◽  
Mucosal Acidification ◽  
Male And Female Rats ◽  
Regulated Expression

Although the morbidity of ulcers is statistically higher in males than females, the mechanism of this difference remains unknown. Recent studies show that duodenal HCO3 - response to mucosal acidification is higher in females than males, and this may be a factor responsible for the sex difference in the mucosal protective mechanisms. In this article, we examined the duodenal HCO3 - responses to various stimuli in male and female rats, including estrogen, and reviewed the mechanisms responsible for the sex difference in the acid-induced HCO3 - secretion. Mucosal acidification was performed by exposing the duodenum to 10 mM HCl for 10 min. PGE2 was administered intravenously, while capsaicin was applied topically to the duodenum for 10 min. Tamoxifen was given s.c. 30 min before the acidification. Ovariectomy was performed 2 weeks before the experiments; half of the animals were given estrogen i.m. after the operation. Mucosal acidification increased duodenal HCO3 - secretion in male rats, and this response was inhibited by indomethacin and sensory deafferentation. Although no sex difference was found in HCO3 - responses to PGE2 and capsaicin, the response to acid was significantly greater in female than male rats. The different HCO3 - response to acid disappeared on ovariectomy, and this effect was totally reversed by the repeated administration of estrogen. The gene expression of ASIC3 in female rats was greater than in male rats and down-regulated by ovariectomy or tamoxifen treatment in an estradiol- dependent manner, while no sex difference was observed in TRPV1 and CFTR expressions. In conclusion, the acid-induced HCO3 - response is greater in female than male rats, and this phenomenon is not due to changes in PGE2 sensitivity or TRPV1/CFTR expressions but may be accounted for by increased expression of ASIC3 on sensory neurons, which is associated with the chronic influence of estrogen.

scholarly journals Gender-Related Differences in BMP Expression and Adult Hippocampal Neurogenesis within Joint-Hippocampal Axis in a Rat Model of Rheumatoid Arthritis

2021 ◽  
Vol 22 (22) ◽  
pp. 12163
Author(s):  
Hrvoje Omrčen ◽  
Sanja Zoričić Cvek ◽  
Lara Batičić ◽  
Sandra Šućurović ◽  
Tanja Grubić Kezele
Keyword(s):  
Rheumatoid Arthritis ◽  
Gender Differences ◽  
Adult Neurogenesis ◽  
Clinical Course ◽  
Disease Onset ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Female Rats ◽  
Male Rats ◽  
Tnf Α

BMPs regulate synovial quiescence and adult neurogenesis in the hippocampus in non-stress conditions. However, changes in BMP expression that are induced by inflammation during rheumatoid arthritis (RA) have not yet been reported. Here, we show that signalling with synovial BMPs (BMP-4 and -7) mediates the effect of systemic inflammation on adult neurogenesis in the hippocampus during pristane-induced arthritis (PIA) in Dark Agouti (DA) rats, an animal model of RA. Moreover, we show gender differences in BMP expressions and their antagonists (Noggin and Gremlin) during PIA and their correlations with the clinical course and IL-17A and TNF-α levels in serum. Our results indicate gender differences in the clinical course, where male rats showed earlier onset and earlier recovery but a worse clinical course in the first two phases of the disease (onset and peak), which correlates with the initial increase of serum IL-17A level. The clinical course of the female rats worsened in remission. Their prolonged symptoms could be a reflection of an increased TNF-α level in serum during remission. Synovial inflammation was greater in females in PIA-remission with greater synovial BMP and antagonist expressions. More significant correlations between serum cytokines (IL-17A and TNF-α), and synovial BMPs and their antagonists were found in females than in males. On the other hand, males showed an increase in hippocampal BMP-4 expression during the acute phase, but both genders showed a decrease in antagonist expressions during PIA in general. Both genders showed a decrease in the number of Ki-67+ and SOX-2+ and DCX+ cells and in the ratio of DCX+ to Ki67+ cells in the dentate gyrus during PIA. However, in PIA remission, females showed a faster increase in the number of Ki67+, SOX-2+, and DCX+ cells and a faster increase in the DCX/Ki67 ratio than males. Both genders showed an increase of hippocampal BMP-7 expression during remission, although males constantly showed greater BMP-7 expression at all time points. Our data show that gender differences exist in the BMP expressions in the periphery–hippocampus axis and in the IL-17A and TNF-α levels in serum, which could imply differences in the mechanisms for the onset and progression of the disease, the clinical course severity, and adult neurogenesis with subsequent neurological complications between genders.

scholarly journals Distinguishing the behavioral potencies of α-pyrrolidino-phenone cathinone stimulants

2020 ◽  
Author(s):  
Michael A Taffe ◽  
Jacques D Nguyen ◽  
Sophia A Vandewater ◽  
Yanabel Grant ◽  
Tobin J Dickerson
Keyword(s):  
Body Temperature ◽  
Subjective Effects ◽  
Designer Drugs ◽  
Female Rats ◽  
Male Rats ◽  
Dependent Manner ◽  
Male And Female ◽  
Male And Female Rats ◽  
Wheel Activity ◽  
Legal Controls

The α-pyrrolidino-phenone cathinone stimulants first came to widespread attention because of bizarre behavior consequent to the use of α-pyrrolidinopentiophenone (α-PVP, "flakka") reported in the popular press. As with other designer drugs, diversification of cathiones has been driven by desireable subjective effects, but also by attempts to stay ahead of legal controls of specific molecules. The α-pyrrolidinohexiophenone (α-PHP) and α-pyrrolidinopropiophenone (α-PPP) compounds have been relatively under-investigated relative to α-PVP and provide a key opportunity to also investigate structure-activity relationships, i.e., how the extension of the alpha carbon chain may affect potency or efficacy. Male and female rats were used to contrast the effects of α-PHP and α-PPP with those of α-PVP in altering wheel activity and effects on spontaneous locomotion and body temperature were assessed in female rats. The α-PHP and α-PVP compounds (5, 10 mg/kg, i.p.) suppressed wheel activity in female and male rats, whereas α-PPP was only effective in female rats. Inhalation of α-PHP or α-PVP by female rats suppressed wheel activity for an abbreviated duration, compared with the injection route. Spontaneous activity was increased in a dose-dependent manner by all three compounds in female rats, and a small decrements in body temperature were observed after the highest dose of all three compounds. These data show that all three of the α-pyrrolidino-phenone cathinones exhibit significant stimulant-like activity in both male and female rats. Differences were minor and were mostly in potency and the duration of activity. Abuse liability is therefore likely to be equivalent for all three pyrrolidino-phenones.

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