Frontiers in Neuroendocrinology最新文献

Cholecystokinin (CCK) is a neuropeptide modulating digestion, glucose levels, neurotransmitters and memory. Recent studies suggest that CCK exhibits neuroprotective effects in Alzheimer’s disease (AD) and Parkinson’s disease (PD). Thus, we review the physiological function and therapeutic potential of CCK. The neuropeptide facilitates hippocampal glutamate release and gates GABAergic basket cell activity, which improves declarative memory acquisition, but inhibits consolidation. Cortical CCK alters recognition memory and enhances audio-visual processing. By stimulating CCK-1 receptors (CCK-1Rs), sulphated CCK-8 elicits dopamine release in the substantia nigra and striatum. In the mesolimbic pathway, CCK release is triggered by dopamine and terminates reward responses via CCK-2Rs. Importantly, activation of hippocampal and nigral CCK-2Rs is neuroprotective by evoking AMPK activation, expression of mitochondrial fusion modulators and autophagy. Other benefits include vagus nerve/CCK-1R-mediated expression of brain-derived neurotrophic factor, intestinal protection and suppression of inflammation. We also discuss caveats and the therapeutic combination of CCK with other peptide hormones.

Early life stress (ELS) is defined as an acute or chronic stressor that negatively impacts a child’s development. ELS is associated with substance use and mental health problems. This narrative literature review focuses on sex and gender differences in the effects of ELS on 1) adolescent neuroendocrine development; 2) pubertal brain maturation; and 3) development of internalizing symptoms and subsequent substance use. We posit that ELS may generate larger hormonal dysregulation in females than males during puberty, increasing internalizing symptoms and substance use. Future research should consider sex and gender differences in neuroendocrine developmental processes when studying the link between ELS and negative health outcomes.

Perinatal depression (PND) and anxiety affect around 20% of women, but available pharmacotherapy is not sufficiently effective in 20–60% of them, indicating a need for better understanding of these diseases. Since stress is a significant risk factor for PND, the aim was to examine the role of biological, environmental and psychological stress in PND and anxiety through a systematic literature search. Overall 210 studies were included, among which numerous rodent studies showed that perinatal stress induced depressive-like and anxious behavior, which was associated with HPA-axis alterations and morphological brain changes. Human studies indicated that the relationship between cortisol and perinatal depression/anxiety was not as clear and with many contradictions, although social and psychological stress were clearly positively associated with PND. Finally, oxytocin, synthetic neuroactive steroid and n-3 PUFA diet have been identified as potentially beneficial in the therapy of PND and anxiety, worth to be investigated in the future.

Higher prevalence of depression in females might be associated with sex-specific cortisol levels. Evidence exists that cortisol levels differ between healthy females and males, however a sex-specific association in depression has not been systematically assessed. Thus, the current study quantifies the existing literature on different cortisol parameters, i.e., basal cortisol, hair cortisol, cortisol awakening response (CAR), and cortisol stress reactivity comparing depressed females and males as well as sex-specific comparisons with healthy controls. Following an extensive literature research, fifty original articles were included. Depressed females had significantly higher hair cortisol, higher CAR, and lower cortisol stress reactivity compared to depressed males. In comparison with sex-matched controls, female patients had significantly higher evening basal cortisol, higher CAR and lower cortisol stress reactivity, and male patients had significantly higher general, morning and evening basal cortisol. Overall, sex as a fundamental driver of cortisol levels in depression needs to be taken into account.

The female reproductive years are characterized by fluctuations in ovarian hormones across the menstrual cycle, which have the potential to modulate neurophysiological and behavioral dynamics. Menstrually-related mood disorders (MRMDs) comprise cognitive-affective or somatic symptoms that are thought to be triggered by the rapid fluctuations in ovarian hormones in the luteal phase of the menstrual cycle. MRMDs include premenstrual syndrome (PMS), premenstrual dysphoric disorder (PMDD), and premenstrual exacerbation (PME) of other psychiatric disorders. Electroencephalography (EEG) non-invasively records in vivo synchronous activity from populations of neurons with high temporal resolution. The present overview sought to systematically review the current state of task-related and resting-state EEG investigations on MRMDs. Preliminary evidence indicates lower alpha asymmetry at rest being associated with MRMDs, while one study points to the effect being luteal-phase specific. Moreover, higher luteal spontaneous frontal brain activity (slow/fast wave ratio as measured by the delta/beta power ratio) has been observed in persons with MRMDs, while sleep architecture results point to potential circadian rhythm disturbances. In this review, we discuss the quality of study designs as well as future perspectives and challenges of supplementing the diagnostic and scientific toolbox for MRMDs with EEG.

The brain and spinal cord (SC) are both targeted by various hormones, including steroid hormones. However, investigations of the modulatory role of hormones on neurobiological functions usually focus only on the brain. The SC received little attention although this structure pivotally controls motor and sensory functions. Here, we critically reviewed key data showing that the process of neurosteroid biosynthesis or neurosteroidogenesis occurring in the SC plays a pivotal role in the modulation of peripheral nerve injury-induced chronic pain (PNICP) or neuropathic pain. Indeed, several active steroidogenic enzymes expressed in the SC produce endogenous neurosteroids that interact with receptors of neurotransmitters controlling pain. The spinal neurosteroidogenesis is differentially regulated during PNICP condition and its blockade modifies painful sensations. The paper suggests that future investigations aiming to develop effective strategies against PNICP or neuropathic pain must integrate in a gender or sex dependent manner the regulatory effects exerted by spinal neurosteroidogenesis.

Post-finasteride syndrome and post-SSRI sexual dysfunction, are two poorly explored clinical conditions in which men treated for androgenetic alopecia with finasteride or for depression with SSRI antidepressants show persistent side effects despite drug suspension (e.g., sexual dysfunction, psychological complaints, sleep disorders). Because of some similarities in the symptoms, common pathological mechanisms are proposed here. Indeed, as discussed, clinical studies and preclinical data obtained so far suggest an important role for brain modulators (i.e., neuroactive steroids), neurotransmitters (i.e., serotonin, and cathecolamines), and gut microbiota in the context of the gut-brain axis. In particular, the observed interconnections of these signals in these two clinical conditions may suggest similar etiopathogenetic mechanisms, such as the involvement of the enzyme converting norepinephrine into epinephrine (i.e., phenylethanolamine N-methyltransferase). However, despite the current efforts, more work is still needed to advance the understanding of these clinical conditions in terms of diagnostic markers and therapeutic strategies.

Bipolar disorder (BD) is worldwide a prevalent mental illness and a leading risk factor for suicide. Over the past three decades, it has been discovered that sex differences exist throughout the entire panorama of BD, but the etiologic regions and mechanisms that generate such differences remain poorly characterized. Available evidence indicates that the dorsolateral prefrontal cortex (DLPFC), a critical region that controls higher-order cognitive processing and mood, exhibits biological disparities between male and female patients with psychiatric disorders, which are highly correlated with the co-occurrence of psychotic symptoms. This review addresses the sex differences in BD concerning epidemiology, cognitive impairments, clinical manifestations, neuroimaging, and laboratory abnormalities. It also provides strong evidence linking DLPFC to the etiopathogenesis of these sex differences. We emphasize the importance of identifying gene signatures using human brain transcriptomics, which can depict sexually different variations, explain sex-biased symptomatic features, and provide novel targets for sex-specific therapeutics.

Advances in neuroendocrinology have led to major discoveries since the 19th century, identifying adaptive loops for maintaining homeostasis. One of the most remarkable discoveries was the concept of neurosteroids, according to which the brain is not only a target but also a source of steroid production. The identification of new membrane steroid targets now underpins the neuromodulatory effects of neurosteroids such as pregnenolone, which is involved in functions mediated by the GPCR CB1 receptor. Structural analysis of steroids is a key feature of their interactions with the phospholipid membrane, receptors and resulting activity. Therefore, mass spectrometry-based methods have been developed to elucidate the metabolic pathways of steroids, the ultimate approach being metabolomics, which allows the identification of a large number of metabolites in a single sample. This approach should enable us to make progress in understanding the role of neurosteroids in the functioning of physiological and pathological processes.

Worldwide, over 150 million adolescent and adult women use oral contraceptives (OC). An association between OC-use and the emergence of symptoms of mental disorders has been suggested. This systematic review and meta-analysis provide an overview of published research regarding symptoms of mental disorders in association with OC-use, factoring the influence of OC types, age of first-use, duration of OC-intake, and previous diagnoses of mental disorders. A systematic literature search was conducted between June-July 2022. 22 studies were included. While most found no significant OC-use effects on mental symptoms, some hinted at OCs as a potential risk. The existing evidence regarding the potential link between progestin-only OC-use and an elevated risk of mental symptoms in comparison to combined OC-use remains inconclusive. However, due to emerging indications suggesting that the formulation of OC might play a role in mental health outcomes, this topic warrants further investigation. Moreover, indications of an increased risk for depressive symptoms in adolescent OC-users should be noted. Hence, while general population effects seem unlikely, they cannot be completely disregarded. The decision on OC-use should depend on the patient's medical history and should be re-evaluated regularly.