An official website of the United States government
The frontal cortex matures late in development, showing dramatic changes after puberty onset, yet few experiments have directly tested the role of pubertal hormones in cortical maturation. One mechanism thought to play a primary role in regulating the maturation of the neocortex is an increase in inhibitory neurotransmission, which alters the balance of excitation and inhibition. We hypothesized that pubertal hormones could regulate maturation of the frontal cortex by this mechanism. Here, we report that manipulations of gonadal hormones do significantly alter the maturation of inhibitory neurotransmission in the cingulate region of the mouse medial frontal cortex, an associative region that matures during the pubertal transition and is implicated in decision making, learning, and psychopathology. We find that inhibitory neurotransmission, but not excitatory neurotransmission, increases onto cingulate pyramidal neurons during peri-pubertal development and that this increase can be blocked by pre-pubertal, but not post-pubertal, gonadectomy. We next used pre-pubertal hormone treatment to model early puberty onset, a phenomenon increasingly observed in girls living in developed nations. We find that pre-pubertal hormone treatment drives an early increase in inhibitory neurotransmission in the frontal cortex, but not the somatosensory cortex, suggesting that earlier puberty can advance cortical maturation in a regionally specific manner. Pre-pubertal hormone treatment also accelerates maturation of tonic inhibition and performance in a frontal-cortex-dependent reversal-learning task. These data provide rare evidence of enduring, organizational effects of ovarian hormones at puberty and provide a potential mechanism by which gonadal hormones could regulate the maturation of the associative neocortex.
more »
« less
Sex Hormones, Neurosteroids, and Glutamatergic Neurotransmission: A Review of the Literature
Glutamatergic dysfunction has been implicated in the pathophysiology of multiple conditions including epilepsy, chronic pain, post-traumatic stress disorder (PTSD), and premenstrual dysphoric disorder (PMDD), raising interest in potential ways of modifying glutamate in the nervous system. Emerging research has suggested an interactive effect between sex hormones and glutamatergic neurotransmission. The objective of this paper was to review existing literature on the mechanism of interaction between sex hormones and glutamatergic neurotransmission, as well as to explore what is known about these interactions in various neurological and psychiatric conditions. This paper summarizes knowledge regarding mechanisms for these effects, and glutamatergic response to direct modulation of sex hormones. Research articles were identified via scholarly databases including PubMed, Google Scholar, and ProQuest. Articles were included if they were original research from peer-reviewed academic journals that dealt with glutamate, estrogen, progesterone, testosterone, neurosteroids, glutamate and sex hormone interactions, or the potential impact of glutamate and sex hormone interactions in the following conditions: chronic pain, epilepsy, PTSD, and PMDD. Current evidence suggests that sex hormones can directly modulate glutamatergic neurotransmission, with specific protective effects against excitotoxicity noted for estrogens. An effect of monosodium glutamate consumption on sex hormone levels has also been demonstrated, suggesting a possible bidirectional effect. Overall, there is a good deal of evidence suggesting a role for sex hormones, and specifically for estrogens, in the modulation of glutamatergic neurotransmission.
more »
« less
- Award ID(s):
- 2050260
- PAR ID:
- 10415120
- Publisher / Repository:
- Karger
- Date Published:
- Journal Name:
- Neuroendocrinology
- Volume:
- 113
- Issue:
- 9
- ISSN:
- 0028-3835
- Page Range / eLocation ID:
- 905 to 914
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract:Neuropsychiatric disorders, which are associated with stress hormone dysregulation, occurat different rates in men and women. Moreover, nowadays, preclinical and clinical evidence demonstratesthat sex and gender can lead to differences in stress responses that predispose males andfemales to different expressions of similar pathologies. In this curated review, we focus on what isknown about sex differences in classic mechanisms of stress response, such as glucocorticoid hormonesand corticotrophin-releasing factor (CRF), which are components of the hypothalamicpituitary-adrenal (HPA) axis. Then, we present sex differences in neurotransmitter levels, such as serotonin,dopamine, glutamate and GABA, as well as indices of neurodegeneration, such as amyloid βand Tau. Gonadal hormone effects, such as estrogens and testosterone, are also discussed throughoutthe review. We also review in detail preclinical data investigating sex differences caused by recentlyrecognizedregulators of stress and disease, such as the immune system, genetic and epigenetic mechanisms,as well neurosteroids. Finally, we discuss how understanding sex differences in stress responses,as well as in pharmacology, can be leveraged into novel, more efficacious therapeutics forall. Based on the supporting evidence, it is obvious that incorporating sex as a biological variable intopreclinical research is imperative for the understanding and treatment of stress-related neuropsychiatricdisorders, such as depression, anxiety and Alzheimer’s disease.more » « less
-
null (Ed.)Opioid use disorder (OUD) is a debilitating disorder that affects millions of people. Neutral cues can acquire motivational properties when paired with the positive emotional effects of drug intoxication to stimulate relapse. However, much less research has been devoted to cues that become conditioned to the aversive effects of opioid withdrawal. We argue that environmental stimuli promote motivation for opioids when cues are paired with withdrawal (conditioned withdrawal) and generate opioid consumption to terminate conditioned withdrawal (conditioned negative reinforcement). We review evidence that cues associated with pain drive opioid consumption, as patients with chronic pain may misuse opioids to escape physical and emotional pain. We highlight sex differences in withdrawal-induced stress reactivity and withdrawal cue processing and discuss neurocircuitry that may underlie withdrawal cue processing in dependent individuals. These studies highlight the importance of studying cues associated with withdrawal in dependent individuals and point to areas for exploration in OUD research.more » « less
-
Abstract Chemical biomarkers in the central nervous system can provide valuable quantitative measures to gain insight into the etiology and pathogenesis of neurological diseases. Glutamate, one of the most important excitatory neurotransmitters in the brain, has been found to be upregulated in various neurological disorders, such as traumatic brain injury, Alzheimer's disease, stroke, epilepsy, chronic pain, and migraines. However, quantitatively monitoring glutamate release in situ has been challenging. This work presents a novel class of flexible, miniaturized probes inspired by biofuel cells for monitoring synaptically released glutamate in the nervous system. The resulting sensors, with dimensions as low as 50 by 50 μm, can detect real‐time changes in glutamate within the biologically relevant concentration range. Experiments exploiting the hippocampal circuit in mice models demonstrate the capability of the sensors in monitoring glutamate release via electrical stimulation using acute brain slices. These advances could aid in basic neuroscience studies and translational engineering, as the sensors provide a diagnostic tool for neurological disorders. Additionally, adapting the biofuel cell design to other neurotransmitters can potentially enable the detailed study of the effect of neurotransmitter dysregulation on neuronal cell signaling pathways and revolutionize neuroscience.more » « less
-
Maternal hormones such as estrogens deposited into the yolk of turtle eggs follow circulating levels in adult females, and they may alter the sexual fate of developing embryos in species with temperature-dependent sex determination (TSD). In temperate regions, this deposition occurs during the spring when estrogens increase in adult females as ambient temperatures rise, drop after the first clutch, and peak again (albeit less) in the fall. Global warming alters turtle nesting phenology (inducing earlier nesting), but whether it affects circulating hormones remains unknown, hindering our understanding of all potential challenges posed by climate change and the adaptive potential (or lack thereof) of turtle populations. Here, we addressed this question in painted turtles (Chrysemys picta) by quantifying estradiol, estrone, and testosterone via mass spectrometry in the blood of wild adult females exposed to 26 °C and 21 °C in captivity between mid-August and mid-October (15 females per treatment). Results from ANOVA and pairwise comparisons revealed no differences between treatments in circulating hormones measured at days 0, 2, 7, 14, 28, and 56 of the experiment. Further research is warranted (during the spring, using additional temperatures) before concluding that females are truly buffered against the indirect risk of climate change via maternal hormone allocation.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1159/000531148
