The transition to motherhood: linking hormones, brain and behaviour

https://doi.org/10.1016/j.yfrne.2023.101060

Progesterone and contraceptive progestin actions on the brain: A systematic review of animal studies and comparison to human neuroimaging studies

The hippocampus hosts the continuous addition of new neurons throughout life—a phenomenon named adult hippocampal neurogenesis (AHN). Here we revisit the occurrence of AHN in more than 110 mammalian species, including humans, and discuss the further validation of these data by single‐cell RNAseq and other alternative techniques. In this regard, our recent studies have addressed the long‐standing controversy in the field, namely whether cells positive for AHN markers are present in the adult human dentate gyrus (DG). Here we review how we developed a tightly controlled methodology, based on the use of high‐quality brain samples (characterized by short postmortem delays and ≤24 h of fixation in freshly prepared 4% paraformaldehyde), to address human AHN. We review that the detection of AHN markers in samples fixed for 24 h required mild antigen retrieval and chemical elimination of autofluorescence. However, these steps were not necessary for samples subjected to shorter fixation periods. Moreover, the detection of labile epitopes (such as Nestin) in the human hippocampus required the use of mild detergents. The application of this strictly controlled methodology allowed reconstruction of the entire AHN process, thus revealing the presence of neural stem cells, proliferative progenitors, neuroblasts, and immature neurons at distinct stages of differentiation in the human DG. The data reviewed here demonstrate that methodology is of utmost importance when studying AHN by means of distinct techniques across the phylogenetic scale. In this regard, we summarize the major findings made by our group that emphasize that overlooking fundamental technical principles might have consequences for any given research field.

Methods to study adult hippocampal neurogenesis in humans and across the phylogeny

Ferroptosis is a type of regulated cell death that is dependent on iron and reactive oxygen species (ROS). Melatonin (N-acetyl-5-methoxytryptamine) reduces hypoxic-ischemic brain damage via mechanisms that involve free radical scavenging. How melatonin regulates radiation-induced ferroptosis of hippocampal neurons is yet to be elucidated. In this study, the mouse hippocampal neuronal cell line HT-22 was treated with 20μM melatonin before being stimulated with a combination of irradiation and 100 μM FeCl3. Furthermore, in vivo experiments were performed in mice treated with melatonin via intraperitoneal injection, which was followed by radiation exposure. A series of functional assays, including CCK-8, DCFH-DA kit, flow cytometry, TUNEL staining, iron estimations, and transmission electron microscopy, were performed on cells as well as hippocampal tissues. The interactions between PKM2 and NRF2 proteins were detected using a coimmunoprecipitation (Co-IP) assay. Moreover, chromatin immunoprecipitation (ChIP), a luciferase reporter assay, and an electrophoretic mobility shift assay (EMSA) were performed to explore the mechanism by which PKM2 regulates the NRF2/GPX4 signaling pathway. The spatial memory of mice was evaluated using the Morris Water Maze test. Hematoxylin-eosin and Nissl staining were performed for histological examination. The results revealed that melatonin protected HT-22 neuronal cells from radiation-induced ferroptosis, as inferred from increased cell viability, decreased ROS production, reduced number of apoptotic cells, and less cristae, higher electron density in mitochondria. In addition, melatonin induced PKM2 nuclear transference, while PKM2 inhibition reversed the effects of melatonin. Further experiments demonstrated that PKM2 bound to and induced the nuclear translocation of NRF2, which regulated GPX4 transcription. Ferroptosis enhanced by PKM2 inhibition was also converted by NRF2 overexpression. In vivo experiments indicated that melatonin alleviated radiation-induced neurological dysfunction and injury in mice. In conclusion, melatonin suppressed ferroptosis to decrease radiation-induced hippocampal neuronal injury by activating the PKM2/NRF2/GPX4 signaling pathway. 

Melatonin reduces radiation-induced ferroptosis in hippocampal neurons by activating the PKM2/NRF2/GPX4 signaling pathway

Background and Objective Weight loss-related amenorrhea is defined as the reversible functional inhibition of the hypothalamic-pituitary-ovarian (HPO) axis associated with weight loss or low body weight, which occurs mostly in adolescents and women of reproductive age. The specific pathological mechanisms of this disease have not yet been elucidated, and the optimal evidence-based guidelines for its clinical assessment and management are limited. This review summarizes its adverse effects on female health, and the individualized, emerging, and multidisciplinary therapeutic approaches used to treat it. Methods We searched the PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) databases for Chinese and English literature on functional hypothalamic amenorrhea (FHA), and retrieved original articles (on basic and clinical research) and reviews published up to December 2022. Key Content and Findings We reviewed the findings on the unfavorable effects of weight loss-related amenorrhea with a focus on reproduction, the skeletal and cardiovascular system, other endocrine effects, and mental health. Lifestyle changes and hormonal replacement have been shown to alleviate the underlying causes and lead to the recovery of menstruation. However, the efficacy of treatments is affected by many factors, such as psychological stress and heterogeneity. Conclusions Weight loss-related amenorrhea, which is an important type of FHA, is manifested by anovulation and hypoestrogenism, and has both short- and long-term adverse effects on women’s overall health. It is difficult to alleviate its underlying causes. Individualized treatments need to be optimized and emerging or multidisciplinary therapeutic approaches need to be explored that aim to recover normal menstruation and ovulation, eliminate the undesirable effects of prolonged hypoestrogenism and alleviate psychological disorders.

The effects of weight loss-related amenorrhea on women’s health and the therapeutic approaches: a narrative review

The levels of reproduction-associated hormones in females, such as estrogen, progesterone, prolactin, and oxytocin, change dramatically during pregnancy and postpartum. Reproduction-associated hormones can affect adult hippocampal neurogenesis (AHN), thereby regulating mothers' behavior after delivery. In this review, we first briefly introduce the overall functional significance of AHN and the methods commonly used to explore this front. Then, we attempt to reconcile the changes of reproduction-associated hormones during pregnancy. We further update the findings on how reproduction-related hormones influence adult hippocampal neurogenesis. This review is aimed at emphasizing a potential role of AHN in reproduction-related brain plasticity and its neurobiological relevance to motherhood behavior.

/pdf/reproduction-associated-hormones-and-adult-hippocampal-4823zjgeit.pdf

Reproduction-Associated Hormones and Adult Hippocampal Neurogenesis.

Extracranial 125I Seed Implantation Allows Non-invasive Stereotactic Radioablation of Hippocampal Adult Neurogenesis in Guinea Pigs

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Reproduction-Associated Hormones and Adult Hippocampal Neurogenesis.

Extracranial 125I Seed Implantation Allows Non-invasive Stereotactic Radioablation of Hippocampal Adult Neurogenesis in Guinea Pigs