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BioRxiv : the Preprint Server For... May 2023Cyclic changes in hormonal state are well-known to regulate mating behavior during the female reproductive cycle, but whether and how these changes affect the dynamics...
Cyclic changes in hormonal state are well-known to regulate mating behavior during the female reproductive cycle, but whether and how these changes affect the dynamics of neural activity in the female brain is largely unknown. The ventromedial hypothalamus, ventro-lateral subdivision (VMHvl) contains a subpopulation of VMHvl neurons that controls female sexual receptivity. Longitudinal single cell calcium imaging of these neurons across the estrus cycle revealed that overlapping but distinct subpopulations were active during proestrus (mating-accepting) vs. non-proestrus (rejecting) phases. Dynamical systems analysis of imaging data from proestrus females uncovered a dimension with slow ramping activity, which generated approximate line attractor-like dynamics in neural state space. During mating, the neural population vector progressed along this attractor as male mounting and intromission proceeded. Attractor-like dynamics disappeared in non-proestrus states and reappeared following re-entry into proestrus. They were also absent in ovariectomized females but were restored by hormone priming. These observations reveal that hypothalamic line attractor-like dynamics are associated with female sexual receptivity and can be reversibly regulated by sex hormones, demonstrating that attractor dynamics can be flexibly modulated by physiological state. They also suggest a potential mechanism for the neural encoding of female sexual arousal.
PubMed: 37292695
DOI: 10.1101/2023.05.22.541741 -
Scientific Reports Jul 2018Exercise physiology is different in males and females. Females are poorly studied due to the complexity of the estrous cycle and this bias has created an exercise sex...
Exercise physiology is different in males and females. Females are poorly studied due to the complexity of the estrous cycle and this bias has created an exercise sex gap. Here, we evaluated the impact of sexual dimorphism and of the estrous cycle on muscle strength and running power of C57BL/6 mice. Like men, male mice were stronger and more powerful than females. Exercise-induced increase of O consumption ([Formula: see text]O) and CO production ([Formula: see text]CO) were equal between sexes, indicating that running economy was higher in males. Thermoregulation was also more efficient in males. In females, proestrus increased exercise [Formula: see text]O and [Formula: see text]CO at low running speeds (30-35% female [Formula: see text]O) and estrus worsened thermoregulation. These differences translated into different absolute and relative workloads on the treadmill, even at equal submaximal [Formula: see text]O and belt speeds. In summary, our results demonstrate the better muscle strength, running power and economy, and exercise-induced thermoregulation of males compared to females. Proestrus and estrus still undermined the running economy and exercise-induced thermoregulation of females, respectively. These results demonstrate an important exercise sex gap in mice.
Topics: Animals; Carbon Dioxide; Estrous Cycle; Female; Heart Rate; Male; Mice; Mice, Inbred C57BL; Models, Animal; Muscle Strength; Muscle, Skeletal; Oxygen Consumption; Physical Conditioning, Animal; Running; Sex Factors
PubMed: 30013130
DOI: 10.1038/s41598-018-29050-0 -
The European Journal of Neuroscience Apr 2018In humans and animal models, sex differences are reported for anxiety-like behavior and response to anxiogenic stimuli. In the current work, we studied anxiety-like...
In humans and animal models, sex differences are reported for anxiety-like behavior and response to anxiogenic stimuli. In the current work, we studied anxiety-like behavior and response to the prototypical anti-anxiety drug, diazepam. We used 6th generation outbred lines of adult Long Evans rats with high and low anxiety-like behavior phenotypes to investigate the impact of proestrus on the baseline and diazepam-induced behavior. At three doses of diazepam (0, 0.1, and 1.0 mg/kg, i.p.), we measured anxiogenic responses on the elevated plus maze of adult male and female rats. We assessed parvalbumin and brain-derived neurotrophin protein levels in forebrain and limbic structures implicated in anxiety/stress using immunohistochemistry. At baseline, we saw significant differences between anxiety lines, with high anxiety lines displaying less time on the open arms of the elevated plus maze, and less open arm entries, regardless of sex. During proestrus, high anxiety females showed less anxiety-like behavior at 0.1 mg/kg, while low anxiety females displayed less anxiety-like behavior at 0.1 and 1.0 doses, relative to males. Brain-derived neurotrophin protein was elevated in females in the medial prefrontal cortex and central amygdala, while parvalbumin-immunoreactive cells were greater in males in the medial prefrontal cortex. Parvalbumin-positive cells in high anxiety females were higher in CA2 and dentate gyrus relative to males from the same line. In sum, when tested in proestrus, females showed greater anxiolytic effects of diazepam relative to males, and this correlated with increases in neurotrophin and parvalbumin neuron density in corticolimbic structures.
Topics: Animals; Animals, Inbred Strains; Anti-Anxiety Agents; Behavior, Animal; Brain; Brain-Derived Neurotrophic Factor; Diazepam; Dose-Response Relationship, Drug; Female; Male; Neurons; Parvalbumins; Proestrus; Rats; Sex Characteristics
PubMed: 29461650
DOI: 10.1111/ejn.13870 -
Translational Research : the Journal of... Aug 2021Nociception and opioid antinociception in females are pliable processes, varying qualitatively and quantitatively over the reproductive cycle. Spinal estrogenic... (Review)
Review
Nociception and opioid antinociception in females are pliable processes, varying qualitatively and quantitatively over the reproductive cycle. Spinal estrogenic signaling via membrane estrogen receptors (mERs), in combination with multiple other signaling molecules [spinal dynorphin, kappa-opioid receptors (KOR), glutamate and metabotropic glutamate receptor 1 (mGluR)], appears to function as a master coordinator, parsing functionality between pronociception and antinociception. This provides a window into pharmacologically accessing intrinsic opioid analgesic/anti-allodynic systems. In diestrus, membrane estrogen receptor alpha (mERα) signals via mGluR to suppress spinal endomorphin 2 (EM2) analgesia. Strikingly, in the absence of exogenous opioids, interfering with this suppression in a chronic pain model elicits opioid anti-allodynia, revealing contributions of endogenous opioid(s). In proestrus, robust spinal EM2 analgesia is manifest but this requires spinal dynorphin/KOR and glutamate-activated mGluR. Furthermore, spinal mGluR blockade in a proestrus chronic pain animal (eliminating spinal EM2 analgesia) exacerbates mechanical allodynia, revealing tempering by endogenous opioid(s). A complex containing mu-opioid receptor, KOR, aromatase, mGluRs, and mERα are foundational to eliciting endogenous opioid anti-allodynia. Aromatase-mERα oligomers are also plentiful, in a central nervous system region-specific fashion. These can be independently regulated and allow estrogens to act intracellularly within the same signaling complex in which they are synthesized, explaining asynchronous relationships between circulating estrogens and central nervous system estrogen functionalities. Observations with EM2 highlight the translational relevance of extensively characterizing exogenous responsiveness to endogenous opioids and the neuronal circuits that mediate them along with the multiplicity of estrogenic systems that concomitantly function in phase and out-of-phase with the reproductive cycle.
Topics: Analgesia; Analgesics; Animals; Central Nervous System; Chronic Pain; Estrogens; Female; Glutamates; Humans; Male; Models, Neurological; Nociception; Opioid Peptides; Receptors, Estrogen; Receptors, Glutamate; Receptors, Opioid; Translational Research, Biomedical
PubMed: 33567346
DOI: 10.1016/j.trsl.2021.02.002 -
Neuroscience Feb 2020Aging is a well-recognized risk factor for sleep disruption. The characteristics of sleep in aging include its disruption by frequent awakenings, a decline in both...
Aging is a well-recognized risk factor for sleep disruption. The characteristics of sleep in aging include its disruption by frequent awakenings, a decline in both non-rapid eye movement (nonREM) and REM sleep amounts, and a weaker homeostatic response to sleep loss. Evidence also suggests that sleep in females is more sensitive to changes in the ovarian steroidal milieu. The Fischer-344 rats are commonly used experimental subjects in behavioral and physiological studies, including sleep and aging. Most sleep studies in Fischer-344 rats have used male subjects to avoid interactions between the estrus and sleep-waking cycles. The changes in the sleep-wake organization of female Fischer-344 rats, especially with advancing age, are not well-characterized. We determined sleep-waking features of cycling females across estrus stages. We also compared spontaneous and homeostatic sleep response profiles of young (3-4 months) and old (24-25 months) male and female Fischer-344 rats. The results suggest that: i) sleep-wake architectures across stages of estrus cycle in young females were largely comparable except for a significant suppression of REM sleep at proestrus night and an increase in REM sleep the following day; ii) despite hormonal differences, sleep-wake architecture in male and female rats of corresponding ages were comparable except for the suppression of REM sleep at proestrus night and higher nonREM delta power in recovery sleep; and iii) aging significantly affected sleep-wake amounts, sleep-wake stability, and homeostatic response to sleep loss in both male and female rats and that the adverse effects of aging were largely comparable in both sexes.
Topics: Aging; Animals; Estrous Cycle; Female; Male; Rats; Rats, Inbred F344; Sex Factors; Sleep; Sleep Deprivation; Sleep Stages; Sleep, REM; Wakefulness
PubMed: 31846749
DOI: 10.1016/j.neuroscience.2019.11.046 -
Folia Histochemica Et Cytobiologica 2009There are a lot of factors affecting the release of hormones from the anterior part of pituitary gland and their interactions with other parts of the endocrine, nervous... (Review)
Review
There are a lot of factors affecting the release of hormones from the anterior part of pituitary gland and their interactions with other parts of the endocrine, nervous and immune systems. The special significance of the proestrus phase of the estrous cycle of the rat, during which LH and FSH levels increase, followed by ovulation is known. The short length of the estrous cycle and the well recognized sequence of vaginal lavage cytology make it useful for investigating the influence of a stressful environment on the reproductive function. Short duration and mild changes in environmental conditions is considered as a factor analogous to psychological stress. The study was undertaken to determine the effects of a short duration change in the ambient temperature and oxygenation (30 minutes) on the proestrus phase of reproductive cycle and on the repeatability and regularity of phases of the reproductive cycle of Wistar strain rats. The animals were kept under standard conditions and had food and water available ad libitum. The climatic chamber with automatically adjustable and monitored internal parameters (temperature, oxygenation, humidity) was used to develop stress conditions. An estimation of the vaginal lavage using the microscope was done to determine the estrous cycle. The animals were divided into 6 groups. On the day of experiment: the control group (CG) stayed in the climatic chamber for 30 minutes (ambient temperature 21 degrees C, normoxia - 21% O(2)), the five test groups (TG - I - V) remained in the climatic chamber for 30 minutes, in the established environmental conditions (I - 21 degrees C, 10% O(2); II - 10 degrees C, 21% O(2); III - 10 degrees C, 10% O(2); IV - 35 degrees C, 21% O(2); V - 35 degrees C, 10% O(2)). During the following days after the experiment, a microscopic estimation of vaginal lavage was collected over again. There were no changes of duration and sequence of the present estrous cycle and repeatability of the next cycles. Our results indicate that short duration change in the ambient conditions do not cause a disturbance in the hypothalamo - pituitary - gonadal axis, although it can activate adaptation mechanisms of the organism.
Topics: Adaptation, Physiological; Animals; Estrous Cycle; Female; Oxygen; Proestrus; Rats; Rats, Wistar; Stress, Physiological; Temperature; Time Factors
PubMed: 19995706
DOI: 10.2478/v10042-009-0017-z -
Strain and sex based characterization of behavioral expressions in non-induced compulsive-like mice.Physiology & Behavior Jan 2017There is currently a lack of understanding how genetic background and sex differences attribute to the heterogeneity of obsessive-compulsive disorder (OCD). An animal...
There is currently a lack of understanding how genetic background and sex differences attribute to the heterogeneity of obsessive-compulsive disorder (OCD). An animal model of compulsive-like behaviors has been developed through bidirectional selection of house mice (Mus musculus) for high (big cotton nests; BIG mice) and low levels (small nests; SMALL mice) of nest-building behavior. The BIG male strains have predictive and face validity as a spontaneous animal model of OCD. Here, we evaluated compulsive-, anxiety-, cognitive-, and depression-like behaviors among male and proestrus female replicate strains each of BIG (BIG1, BIG2) and SMALL (SML1, SML2) nest-builders, and randomly-bred Controls (C1, C2). BIG1 and BIG2 males and females had higher nesting scores when compared to SMALL and Control strains. Male BIG1 and BIG2 strains showed more compulsive-like nesting than BIG1 and BIG2 proestrus females, which was not observed among the other strains. Nesting scores were also different between BIG replicate male strains. A similar pattern was observed in the compulsive-like marble burying behavior with BIG strains burying more marbles than SMALL and Control strains. Significant replicate and sex differences were also observed in marble burying among the BIG strains. The open field test revealed replicate effects while the BIG strains showed less anxiety-like behavior in the elevated plus maze test compared to the SMALL strains. For novel object recognition only the Control strains showed replicate and sex differences. In the depression-like forced swim test proestrus females demonstrated less depression-like behavior than males. BIG and SMALL nest-building strains had a higher corticosterone stress response than the Control strains. Together these results indicate a strong interplay of genetic background and sex in influencing expression of behaviors in our compulsive-like mouse model. These results are in congruence with the clinical heterogeneity of OCD.
Topics: Analysis of Variance; Animals; Corticosterone; Depression; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Estrous Cycle; Exploratory Behavior; Female; Male; Maze Learning; Mice; Nesting Behavior; Obsessive-Compulsive Disorder; Sex Characteristics; Species Specificity
PubMed: 27838311
DOI: 10.1016/j.physbeh.2016.11.002 -
Cannabis and Cannabinoid Research Feb 2024Endocannabinoids and exogenous cannabinoids are potent regulators of feeding behavior and energy metabolism. Stimulating cannabinoid receptor signaling enhances...
Endocannabinoids and exogenous cannabinoids are potent regulators of feeding behavior and energy metabolism. Stimulating cannabinoid receptor signaling enhances appetite, particularly for energy-dense palatable foods, and promotes energy storage. To elucidate the underlying cellular mechanisms, we investigate here the potential role of astrocytic endocannabinoid 2-arachidonoylglycerol (2-AG). Astrocytes provide metabolic support for neurons and contribute to feeding regulation but the effect of astrocytic 2-AG on feeding is unknown. We generated mice lacking the 2-AG synthesizing enzyme diacylglycerol lipase alpha () in astrocytes (GLAST-Dagla KO) and investigated hedonic feeding behavior in male and female mice. Body weight and baseline water and food intake was characterized; additionally, the mice went through milk, saccharine, and sucrose preference tests in fed and fasted states. In female mice, the estrous cycle stages were identified and plasma levels of female sex hormones were measured. We found that the effects of the inducible astrocytic deletion were sex-specific. Acute milk preference was decreased in female, but not in male mice and the effect was most evident in the estrus stage of the cycle. This prompted us to investigate sex hormone profiles, which were found to be altered in GLAST-Dagla KO females. Specifically, follicle-stimulating hormone was elevated in the estrus stage, luteinizing hormone in the proestrus, and progesterone was increased in both proestrus and estrus stages of the cycle compared with controls. Astrocytic regulates acute hedonic appetite for palatable food in females and not in males, possibly owing to a deregulated female sex hormone profile. It is plausible that endocannabinoid production by astrocytes at least partly contributes to the greater susceptibility to overeating in females. This finding may also be important for understanding the effects of exogenous cannabinoids on sex hormone profiles.
Topics: Mice; Male; Female; Animals; Endocannabinoids; Astrocytes; Cannabinoids; Hyperphagia; Gonadal Steroid Hormones
PubMed: 38265773
DOI: 10.1089/can.2023.0194 -
Cellular and Molecular Neurobiology Jul 2012There are clear sex differences in incidence and onset of stress-related and other psychiatric disorders in humans. Yet, rodent models for psychiatric disorders are... (Review)
Review
There are clear sex differences in incidence and onset of stress-related and other psychiatric disorders in humans. Yet, rodent models for psychiatric disorders are predominantly based on male animals. The strongest argument for not using female rodents is their estrous cycle and the fluctuating sex hormones per phase which multiplies the number of animals to be tested. Here, we will discuss studies focused on sex differences in emotionality and cognitive abilities in experimental conditions with and without stress. First, female sex hormones such as estrogens and progesterone affect emotions and cognition, contributing to sex differences in behavior. Second, females respond differently to stress than males which might be related to the phase of the estrous cycle. For example, female rats and mice express less anxiety than males in a novel environment. Proestrus females are less anxious than females in the other estrous phases. Third, males perform in spatial tasks superior to females. However, while stress impairs spatial memory in males, females improve their spatial abilities, depending on the task and kind of stressor. We conclude that the differences in emotion, cognition and responses to stress between males and females over the different phases of the estrous cycle should be used in animal models for stress-related psychiatric disorders.
Topics: Animals; Cognition; Emotions; Female; Gonadal Steroid Hormones; Humans; Male; Neuronal Plasticity; Receptors, Steroid; Stress, Psychological
PubMed: 22113371
DOI: 10.1007/s10571-011-9774-2 -
Molecular Medicine (Cambridge, Mass.) 2008Trauma-hemorrhage leads to prolonged immune suppression, sepsis, and multiple organ failure. The condition affects all compartments of the immune system, and extensive... (Review)
Review
Trauma-hemorrhage leads to prolonged immune suppression, sepsis, and multiple organ failure. The condition affects all compartments of the immune system, and extensive studies have been carried out elucidating the immunological events following trauma-hemorrhage. The immune alteration observed following trauma-hemorrhage is gender dependent in both animal models and humans, though some studies in humans are contradictory. Within 30 min after trauma-hemorrhage, splenic and peritoneal macrophages, as well as T-cell function, are depressed in male animals, but not in proestrus females. Studies have also shown that the mortality [corrected] rate and the induction of subsequent sepsis following trauma-hemorrhage are significantly higher in males and ovariectomized females compared with proestrus females. These and other investigations show that sex hormones form the basis of this gender dichotomy, and administration of estrogen can ameliorate the immune depression and increase the survival rate after trauma-hemorrhage. This review specifically elaborates the studies carried out thus far demonstrating immunological alteration after trauma-hemorrhage and its modulation by estrogen. Also, estrogen was shown to produce its salutary effects through nuclear as well as extranuclear receptors. Estrogen rapidly activates several protein kinases and phosphatases, as well as the release of calcium in different cell types. The results of the studies exemplify the promise of estrogen as a therapeutic adjunct in treating adverse pathophysiological conditions following trauma-hemorrhage.
Topics: Animals; Dendritic Cells; Estrogens; Hemorrhage; Humans; Immune System; Inflammation; Kupffer Cells; Macrophages; Molecular Structure; Neutrophils; Receptors, Estrogen; Sex Factors; T-Lymphocytes; Wounds and Injuries
PubMed: 18235843
DOI: 10.2119/2008-00001.Raju