Biology subjects

Chaiton, J.

Publications and source records attributed to Chaiton, J..

3 recordsLinked to original sources

bioRxiv2019

Selective activation of estrogen receptors α and β: Implications for depressive-like phenotypes in female mice exposed to chronic unpredictable stress

The estrogen receptor (ER) mechanisms by which 17{beta}-estradiol influences depressive-like behaviour have primarily been investigated acutely and not within an animal model of depression. Therefore, the current study aimed to dissect the contribution of ER and ER{beta} to the effects of 17{beta}-estradiol under non-stress and chronic stress conditions. Ovariectomized (OVX) or sham-operated mice were treated chronically (47 days) with 17{beta}-estradiol (E2), the ER{beta} agonist diarylpropionitrile (DPN), the ER agonist propylpyrazole-triol (PPT), or vehicle. On day 15 of treatment, mice from each group were assigned to Chronic Unpredictable Stress (CUS; 28 days) or non-CUS conditions. Mice were assessed for anxiety- and depressive-like behaviour and hypothalamic-pituitary-adrenal (HPA) axis function. Cytokine and chemokine levels, and postsynaptic density protein 95 were measured in the hippocampus and frontal cortex, and adult hippocampal neurogenesis was assessed. Overall, the effects of CUS were more robust that those of estrogenic treatments, as seen by increased immobility in the tail suspension test (TST), reduced PSD-95 expression, reduced neurogenesis in the ventral hippocampus, and HPA axis negative feedback dysregulation. However, we also observe CUS-dependent and -independent effects of ovarian status and estrogenic treatments. The effects of CUS on PSD-95 expression, the cytokine milieu, and in TST were largely driven by PPT and DPN, indicating that these treatments were not protective. Independent of CUS, estradiol increased neurogenesis in the dorsal hippocampus, blunted the corticosterone response to an acute stressor, but increased anxiety-like behaviour. These findings provide insights into the complexities of estrogen signaling in modulating depressive-like phenotypes under non-stress and chronic stress conditions.

neuroscience↗

bioRxiv2019

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

Androgens (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.

neuroscience↗

bioRxiv2018

Letrozole increases hippocampal neurogenesis in middle-aged female mice

Letrozole, a third-generation aromatase inhibitor, prevents the production of estrogens in the final step in conversion from androgens. Due to its efficacy at suppressing estrogens, letrozole has recently taken favor as a first-line adjuvant treatment for hormone-responsive breast cancer in middle-aged women. Though patient response to letrozole has generally been positive, there is conflicting evidence surrounding its impact on the development of depression. It is possible that letrozoles potential adverse effects on mood are a result of the impact of hormonal fluctuations on neurogenesis in the hippocampus. Thus, to clarify the effects of letrozole on the hippocampus and behavior, we examined how chronic administration affects hippocampal neurogenesis and depressive-like behaviour in middle-aged, intact female mice. Mice were given either letrozole (1mg/kg) or vehicle by injection (ip) daily for 3 weeks. Depressive-like behaviour was assessed during the last 3 days of treatment using the forced swim test, tail suspension test, and sucrose preference test, and the production of new neurons was quantified using the immature neuronal marker, doublecortin (DCX). We found that letrozole increased DCX expression and maturation in the dentate gyrus, but had no significant effect on depressive-like behaviour. Our findings suggest that a reduction in circulating estrogens in middle-aged females increases hippocampal neurogenesis without any adverse impact on behavior; as such, this furthers our understanding of how estrogens modulate neurogenesis, and to the rationale for the utilization of letrozole in the clinical management of breast cancer.

neuroscience↗