-
The Journal of Comparative Neurology May 2023An important factor that can modulate neuron properties is sex-specific hormone fluctuations, including the human menstrual cycle and rat estrous cycle in adult females....
An important factor that can modulate neuron properties is sex-specific hormone fluctuations, including the human menstrual cycle and rat estrous cycle in adult females. Considering the striatal brain regions, the nucleus accumbens (NAc) core, NAc shell, and caudate-putamen (CPu), the estrous cycle has previously been shown to impact relevant behaviors and disorders, neuromodulator action, and medium spiny neuron (MSN) electrophysiology. Whether the estrous cycle impacts MSN dendritic spine attributes has not yet been examined, even though MSN spines and glutamatergic synapse properties are sensitive to exogenously applied estradiol. Thus, we hypothesized that MSN dendritic spine attributes would differ by estrous cycle phase. To test this hypothesis, brains from adult male rats and female rats in diestrus, proestrus AM, proestrus PM, and estrus were processed for Rapid Golgi-Cox staining. MSN dendritic spine density, size, and type were analyzed in the NAc core, NAc shell, and CPu. Overall spine size differed across estrous cycle phases in female NAc core and NAc shell, and spine length differed across estrous cycle phase in NAc shell and CPu. Consistent with previous work, dendritic spine density was increased in the NAc core compared to the NAc shell and CPu, independent of sex and estrous cycle. Spine attributes in all striatal regions did not differ by sex when estrous cycle was disregarded. These results indicate, for the first time, that estrous cycle phase impacts dendritic spine plasticity in striatal regions, providing a neuroanatomical avenue by which sex-specific hormone fluctuations can impact striatal function and disorders.
Topics: Humans; Rats; Female; Male; Animals; Nucleus Accumbens; Dendritic Spines; Rats, Sprague-Dawley; Putamen; Estrous Cycle; Estradiol
PubMed: 36756791
DOI: 10.1002/cne.25460 -
Scientific Reports Aug 2021Stress responses are highly plastic and vary across physiological states. The female estrous cycle is associated with a number of physiological changes including changes...
Stress responses are highly plastic and vary across physiological states. The female estrous cycle is associated with a number of physiological changes including changes in stress responses, however, the mechanisms driving these changes are poorly understood. Corticotropin-releasing hormone (CRH) neurons are the primary neural population controlling the hypothalamic-pituitary-adrenal (HPA) axis and stress-evoked corticosterone secretion. Here we show that CRH neuron intrinsic excitability is regulated over the estrous cycle with a peak in proestrus and a nadir in estrus. Fast inactivating voltage-gated potassium channel (I) currents showed the opposite relationship, with current density being lowest in proestrus compared to other cycle stages. Blocking I currents equalized excitability across cycle stages revealing a role for I in mediating plasticity in stress circuit function over the female estrous cycle.
Topics: Animals; Corticotropin-Releasing Hormone; Estrous Cycle; Female; Hypothalamus; Mice; Neuronal Plasticity; Neurons; Pituitary-Adrenal System; Stress, Physiological
PubMed: 34404890
DOI: 10.1038/s41598-021-96341-4 -
Archives of Razi Institute Jun 2023Because of the mutual relationship between neural inflammation and seizure, this study aimed to determine the effects of intracerebroventricular (ICV) injection of the...
Because of the mutual relationship between neural inflammation and seizure, this study aimed to determine the effects of intracerebroventricular (ICV) injection of the steroidal and non-steroidal anti-inflammatory drugs on pentylenetetrazol (PTZ)-induced seizures during the estrous cycle in rats. A total of 105 adult female Wistar rats were selected and divided into seven groups, including the control (saline), ketorolac tris salt (7.5, 15, and 30 µg), and methylprednisolone acetate (0.15, 0.3, and 0.6 µg), each with four subgroups (proestrus, estrus, metestrus, and diestrus) and three replicates (n=5). After a week of acclimatization, the estrous phase determination and synchronization were performed. Acute epilepsy was inspired by the intraperitoneal injection of 80 mg/kg of PTZ 30 min after the ICV injection of ketorolac and methylprednisolone acetate. The initiation time of myoclonic seizures (ITMS), the initiation time of tonic-clonic seizures (ITTS), seizure duration (SD), and mortality rate (MR) were measured for 30 min. Data were shown as mean±SD and analyzed using One-way ANOVA followed by Tukey-Kramer multiple comparison post hoc test (<0.05). According to the results, ketorolac (15 and 30 µg) and methylprednisolone acetate (0.3 and 0.6 µg) significantly increased the ITTS and ITMS but decreased SD during the estrous cycle, compared to the control (<0.05). Moreover, MR and SD were significantly decreased by ketorolac (7.5, 15, and 30 µg) and methylprednisolone (0.3 and 0.6 µg), compared to the control during the estrous cycle (<0.05). Therefore, it seems that both ketorolac and methylprednisolone possess dose-dependent anticonvulsant effects that may decrease neural inflammation.
Topics: Rats; Female; Animals; Rats, Wistar; Ketorolac; Methylprednisolone Acetate; Estrous Cycle; Seizures; Inflammation; Anti-Inflammatory Agents
PubMed: 38028823
DOI: 10.22092/ARI.2022.360115.2553 -
Frontiers in Behavioral Neuroscience 2022Dopamine has been increasingly recognized as a key neurotransmitter regulating fear/anxiety states. Nevertheless, the influence of sex and estrous cycle differences on...
Dopamine has been increasingly recognized as a key neurotransmitter regulating fear/anxiety states. Nevertheless, the influence of sex and estrous cycle differences on the role of dopamine in fear responses needs further investigation. We aimed to evaluate the effects of sulpiride (a dopaminergic D2-like receptor antagonist) on contextual fear conditioning in females while exploring the influence of the estrous cycle. First, using a contextual fear conditioning paradigm, we assessed potential differences in acquisition, expression, and extinction of the conditioned freezing response in male and female (split in proestrus/estrus and metestrus/diestrus) Wistar rats. In a second cohort, we evaluated the effects of sulpiride (20 and 40 mg/kg) on contextual conditioned fear in females during proestrus/estrus and metestrus/diestrus. Potential nonspecific effects were assessed in motor activity assays (catalepsy and open-field tests). No sex differences nor estrous cycle effects on freezing behavior were observed during the fear conditioning phases. Sulpiride reduced freezing expression in female rats. Moreover, females during the proestrus/estrus phases of the estrous cycle were more sensitive to the effects of sulpiride than females in metestrus/diestrus. Sulpiride did not cause motor impairments. Although no sex or estrous cycle differences were observed in basal conditioned fear expression and extinction, the estrous cycle seems to influence the effects of D2-like antagonists on contextual fear conditioning.
PubMed: 36518813
DOI: 10.3389/fnbeh.2022.1033649 -
BioRxiv : the Preprint Server For... Apr 2024Uterine contraction patterns vary during the ovulatory cycle and throughout pregnancy but prior measurements have produced limited and conflicting information on these...
Uterine contraction patterns vary during the ovulatory cycle and throughout pregnancy but prior measurements have produced limited and conflicting information on these patterns. We combined a virally delivered genetically encoded calcium reporter (GCaMP8m) and ultra-widefield imaging in live nonpregnant mice to characterize uterine calcium dynamics at organ scale throughout the estrous cycle. Prior to ovulation (proestrus and estrus) uterine excitations primarily initiated in a region near the oviduct, but after ovulation (metestrus and diestrus), excitations initiated at loci homogeneously distributed throughout the organ. The frequency of excitation events was lowest in proestrus and estrus, higher in metestrus and highest in diestrus. These results establish a platform for mapping uterine activity, and show that the question of whether there is an anatomically localized trigger for uterine excitations depends on the estrous cycle phase.
PubMed: 38370720
DOI: 10.1101/2024.02.02.578395 -
Hormones and Behavior Mar 2023Research in humans and animals shows differences in impulsive choice, which is a failure to wait for larger, delayed rewards, when comparing males and females. It is...
Research in humans and animals shows differences in impulsive choice, which is a failure to wait for larger, delayed rewards, when comparing males and females. It is possible that fluctuations in sex hormones (estradiol and progesterone) across the reproductive cycle contribute to sex differences in impulsive choice. The current study delivered an impulsive choice task with peak interval trials to female rats while estrous cycles, the rodent reproductive cycle, were tracked over the course of the task. Female rats were more sensitive to changes in delay in the proestrus phase of the estrous cycle and made more larger-later choices when in estrus, particularly when the delay to the smaller reward was short. Estradiol increases dramatically during proestrus while progesterone peaks during estrus, suggesting that estradiol and progesterone may affect impulsive choice through mechanisms such as delay discounting, delay aversion, and/or timing processes. Analyses of timing of the choice task delays showed inconsistent effects of the estrous cycle across delays, suggesting that reward-timing interactions may have complicated how hormone fluctuations affected interval timing. Further research is needed to determine the mechanism underlying increased larger-later choices during the estrus phase, increased delay sensitivity during the proestrus phase, and variability in interval timing across delays and estrous cycle stages.
Topics: Humans; Rats; Female; Animals; Male; Progesterone; Estrous Cycle; Impulsive Behavior; Gonadal Steroid Hormones; Estradiol; Choice Behavior
PubMed: 36669427
DOI: 10.1016/j.yhbeh.2023.105315 -
Neurobiology of Pain (Cambridge, Mass.) 2021Orofacial pain disorders involving trigeminal sensory neurons disproportionately affect women and can be modulated by hormones, especially estrogen (E2). Proinflammatory...
Orofacial pain disorders involving trigeminal sensory neurons disproportionately affect women and can be modulated by hormones, especially estrogen (E2). Proinflammatory mediators, like serotonin (5HT), can act on sensory neurons expressing the transient receptor potential vanilloid 1 (TRPV1) ion channel, resulting in peripheral sensitization. We previously reported peripheral 5HT evokes greater pain behaviors in the hindpaw of female rats during proestrus and estrus, stages when E2 fluctuates. It is unknown if this interaction is comparable in the trigeminal system. We hypothesized that We report 5HT-evoked nocifensive behaviors are significantly higher during estrus and proestrus, which is attenuated by blocking the 5HT receptor. The comparable dose of 5HT was not nociceptive in males unless capsaicin was also administered. When administered with capsaicin, a lower dose of 5HT evoked trigeminal pain behaviors in females during proestrus. Further, basal 5HT content in the vibrissal pad was higher in cycling females compared to males. , E2 enhanced 5HT-potentiated CGRP release from trigeminal neurons, which was not significantly reduced by blocking the 5HT receptor. Our data indicates that estrogen fluctuation influences the pronociceptive effects of 5HT on trigeminal sensory neurons.
PubMed: 34504982
DOI: 10.1016/j.ynpai.2021.100073 -
Journal of the Endocrine Society Apr 2021The etiology of reproductive disorders correlates with weight gain in patients, but the link between reproduction, diet, and weight has been difficult to translate in...
The etiology of reproductive disorders correlates with weight gain in patients, but the link between reproduction, diet, and weight has been difficult to translate in rodents. As rates of childhood obesity and reproductive disorders increase, the need to study the effects of weight and diet on adolescent females is key. Previous studies show that female mice are resistant to high-fat diet-induced weight gain, but the mechanisms are unclear. Literature also suggests that ovarian function is essential to resistance in weight gain, as an ovariectomy leads to a weight-gaining phenotype similar to male mice on a high-fat diet. However, reproductive changes that occur in adolescent mice on high-fat diet have not been assessed. Here, we show that regulation of the estrus cycle via progesterone is critical to metabolic homeostasis in female mice on a high-fat diet. Female mice were put on high-fat diet or control diet for 12 weeks starting at 4 weeks of age. Every 4 weeks, their estrus cycle was tracked and fasting glucose was measured. We found that after 4 weeks on high-fat diet, there was no difference in weight between groups, but an increase in time spent in proestrus and estrus in mice on high-fat diet and an increase in serum progesterone during proestrus. These results show that intact females modulate their estrus cycle in response to a high-fat diet as a mechanism of homeostatic regulation of body weight, protecting them from metabolic abnormalities. Understanding the mechanisms behind this protection may yield therapeutic opportunities for treatment of reproductive disorders in adolescent female patients.
PubMed: 33733019
DOI: 10.1210/jendso/bvab010 -
Frontiers in Molecular Neuroscience 2018Periodic oscillations of gonadal hormone levels during the estrous cycle exert effects on the female brain, impacting cognition and behavior. While previous research...
Periodic oscillations of gonadal hormone levels during the estrous cycle exert effects on the female brain, impacting cognition and behavior. While previous research suggests that changes in hormone levels across the cycle affect dendritic spine dynamics in the hippocampus, little is known about the effects on cortical dendritic spines and previous studies showed contradictory results. In this imaging study, we investigated the impact of the estrous cycle on the density and dynamics of dendritic spines of pyramidal neurons in the primary somatosensory cortex of mice. We also examined if the induction of synaptic plasticity during proestrus, estrus, and metestrus/diestrus had differential effects on the degree of remodeling of synapses in this brain area. We used chronic two-photon excitation (2PE) microscopy during steady-state conditions and after evoking synaptic plasticity by whisker stimulation at the different stages of the cycle. We imaged apical dendritic tufts of layer 5 pyramidal neurons of naturally cycling virgin young female mice. Spine density, turnover rate (TOR), survival fraction, morphology, and volume of mushroom spines remained unaltered across the estrous cycle, and the values of these parameters were comparable with those of young male mice. However, while whisker stimulation of female mice during proestrus and estrus resulted in increases in the TOR of spines (74.2 ± 14.9% and 75.1 ± 12.7% vs. baseline, respectively), sensory-evoked plasticity was significantly lower during metestrus/diestrus (32.3 ± 12.8%). In males, whisker stimulation produced 46.5 ± 20% increase in TOR compared with baseline-not significantly different from female mice at any stage of the cycle. These results indicate that, while steady-state density and dynamics of dendritic spines of layer 5 pyramidal neurons in the primary somatosensory cortex of female mice are constant during the estrous cycle, the susceptibility of these neurons to sensory-evoked structural plasticity may be dependent on the stage of the cycle. Since dendritic spines are more plastic during proestrus and estrus than during metestrus/diestrus, certain stages of the cycle could be more suitable for forms of memory requiring formation and elimination of spines and other stages for forms of memory where retention and/or repurposing of already existing synaptic connections is more pertinent.
PubMed: 29615867
DOI: 10.3389/fnmol.2018.00083 -
Molecular and Cellular Endocrinology Nov 2018Loss of ovarian function has important effects on neurotransmitter production and release with corresponding effects on cognitive performance. To date, there has been...
Loss of ovarian function has important effects on neurotransmitter production and release with corresponding effects on cognitive performance. To date, there has been little direct comparison of the effects of surgical and transitional menopause on neurotransmitter pathways in the brain. In this study, effects on monoamines, monoamine metabolites, and the amino acids tryptophan (TRP) and tyrosine (TYR) were evaluated in adult ovariectomized (OVX) rats and in rats that underwent selective and gradual ovarian follicle depletion by daily injection of 4-vinylcyclohexene-diepoxide (VCD). Tissues from the hippocampus (HPC), frontal cortex (FCX), and striatum (STR) were dissected and analyzed at 1- and 6-weeks following OVX or VCD treatments. Tissues from gonadally intact rats were collected at proestrus and diestrus to represent neurochemical levels during natural states of high and low estrogens. In gonadally intact rats, higher levels of serotonin (5-HT) were detected at proestrus than at diestrus in the FCX. In addition, the ratio of 5-hydroxyindoleacetic acid (5-HIAA)/5HT in the FCX and HPC was lower at proestrus than at diestrus, suggesting an effect on 5-HT turnover in these regions. No other significant differences between proestrus and diestrus were observed. In OVX- and VCD-treated rats, changes were observed which were both brain region- and time point-dependent. In the HPC levels of norepinephrine, 5-HIAA, TRP and TYR were significantly reduced at 1 week, but not 6 weeks, in both OVX and VCD-treated rats relative to proestrus and diestrus. In the FCX, dopamine levels were elevated at 6 weeks after OVX relative to diestrus. A similar trend was observed at 1 week (but not 6 weeks) following VCD treatment. In the STR, norepinephrine levels were elevated at 1 week following OVX, and HVA levels were elevated at 1 week, but not 6 weeks, following VCD treatment, relative to proestrus and diestrus. Collectively, these data provide the first comprehensive analysis comparing the effects of two models of menopause on multiple neuroendocrine endpoints in the brain. These effects likely contribute to effects of surgical and transitional menopause on brain function and cognitive performance that have been reported.
Topics: Amino Acids; Animals; Biogenic Monoamines; Brain; Cyclohexenes; Estrous Cycle; Female; Hippocampus; Hormones; Menopause; Neostriatum; Ovariectomy; Prefrontal Cortex; Rats, Sprague-Dawley; Vinyl Compounds
PubMed: 29738870
DOI: 10.1016/j.mce.2018.05.003