Hormones and Behavior最新文献_第7页

Do combined oral contraceptives have long-term effects? Little evidence of an enduring effect on cognitive function in former users 复方口服避孕药有长期效果吗？几乎没有证据表明它对前使用者的认知功能有持久的影响

IF 2.4 3区医学 Q2 BEHAVIORAL SCIENCES

Hormones and Behavior

Pub Date : 2025-08-01 DOI: 10.1016/j.yhbeh.2025.105800

Elizabeth Hampson

The use of combined oral contraceptives (COCs) is associated with subtle differences in brain activity and in certain cognitive, perceptual, or affective processes among current COC users compared with non-users. Whether any differences persist after the COCs are discontinued is essentially unknown. In a retrospective analysis of a cognitive dataset from healthy adults (N = 221, M_age = 23.78 yrs), we asked whether any residual effects of COC use could be identified in former users (who had discontinued their COCs ∼30 mo prior) on standardized tests of verbal fluency and visuospatial function. A detailed reproductive history was available, including specifics of any past COC use. Cognition was evaluated during the early follicular phase of the menstrual cycle when the ovaries are quiescent and hormone production is lowest. Based on their reproductive history, participants were classified as former users of COCs (N = 86, mean duration of COC use = 29.89 mo), never-users (N = 106, no past use of hormonal contraceptives), or current users (N = 29, currently using a COC, mean duration of COC use = 29.72 mo). All COCs contained either levonorgestrel or a progestin from the norethindrone family, and 30–35 μg/day of ethinyl estradiol. Analysis of covariance (ANCOVA) contrasting cognitive performance in the 3 groups showed that despite the use of androgenic progestins and an estradiol dose that was relatively high, there was no evidence of a difference between former-users and never-users on any of the cognitive tests. Current users scored lower than former or never users on a conventional visuospatial task (Space Relations). Partial correlations controlling for age, estimated IQ, and pregnancy history revealed that duration of past COC use in former users was significantly associated with verbal fluency on one of two phonemic fluency tasks administered. A longer duration of COC use was associated with poorer word generation ability. This dataset produced little evidence of any enduring effects of COC use, however a duration-dependent association between former COC use and verbal fluency reinforces a similar trend reported previously among current users.

复方口服避孕药（COCs）的使用与当前COCs使用者与非使用者在大脑活动和某些认知、知觉或情感过程中的细微差异有关。在停用COCs后是否存在任何差异基本上是未知的。在对健康成人（N = 221，年龄= 23.78岁）认知数据集的回顾性分析中，我们询问在语言流畅性和视觉空间功能的标准化测试中，是否可以在前使用者（在此之前30个月停止使用COC）中发现COC使用的任何残留影响。有详细的生育史，包括过去使用COC的具体情况。在月经周期的早期卵泡期评估认知能力，此时卵巢处于静止状态，激素分泌最低。根据生殖史，参与者被分为既往COC使用者（N = 86，平均COC使用时间为29.89个月）、从未使用过COC者（N = 106，过去没有使用过激素避孕药）和当前使用者（N = 29，目前正在使用COC，平均COC使用时间为29.72个月）。所有COCs均含有左炔诺孕酮或炔诺酮家族的黄体酮，以及30-35 μg/天的炔雌醇。对比三组认知表现的协方差分析（ANCOVA）显示，尽管使用了雄激素孕激素和雌二醇剂量相对较高，但在任何认知测试中，没有证据表明前使用者和从未使用者之间存在差异。在传统的视觉空间任务（空间关系）中，当前用户的得分低于以前或从未使用过的用户。控制年龄、估计智商和怀孕史的部分相关性显示，前使用者过去COC使用的持续时间与执行的两个音位流畅性任务之一的语言流畅性显着相关。使用COC的时间越长，单词生成能力越差。该数据集几乎没有证据表明使用COC有任何持久的影响，然而，以前使用COC与语言流利度之间的持续依赖关系强化了之前在当前用户中报道的类似趋势。

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引用次数: 0

Multiparity alters expression of corticotropin releasing factor receptor 1 and co-expression with oxytocin neurons in mice 多胎改变小鼠促肾上腺皮质激素释放因子受体1的表达及其与催产素神经元的共表达

IF 2.4 3区医学 Q2 BEHAVIORAL SCIENCES

Hormones and Behavior

Pub Date : 2025-07-29 DOI: 10.1016/j.yhbeh.2025.105799

Katherine E. Parra , Jennifer J. Lafrican , Krystyna A. Rybka , Amaya E. Neuwirth , Lauren S. Chait , Ariana V. Della Posta , Annette L. Greenwood , Kristen L. Zuloaga , Nicholas J. Justice , Damian G. Zuloaga

Corticotropin releasing factor (CRF) signaling through its primary receptor (CRFR1) regulates various stress-related behaviors and neuroendocrine responses. CRFR1 is also a key regulator of stress-related behavior changes during the postpartum period in rodents. Previous studies indicate dynamic changes in CRFR1 in various brain regions during the first postpartum period including an emergence of CRFR1 expression in hypothalamic oxytocin neurons. We sought to determine how these changes in CRFR1 and CRFR1/oxytocin co-expression might be altered with repeated breeding cycles and whether these neural adaptations coincide with changes in maternal behaviors that are reported to occur in rodent dams with greater maternal experience. CRFR1-GFP reporter mice were bred to produce 1 (primiparous) or 3 (multiparous) litters and were assessed for pup retrieval in unstressed and stressed (male intruder) conditions. Brains of nulliparous, primiparous, and multiparous mice were collected to assess CRFR1-GFP and co-expression of CRFR1 with oxytocin. No statistically significant changes in pup retrieval were found between primiparous and multiparous mice although both groups showed a greater latency to hover over pups following male intruder exposure. However, multiparity increased oxytocin/CRFR1 co-expression relative to primiparous and nulliparous mice in the paraventricular hypothalamus (PVN) and supraoptic nucleus (SON). Multiparous mice also showed elevated CRFR1-GFP in the PVN and SON relative to primiparous mice. In the medial preoptic area and anteroventral periventricular nucleus, primiparous, but not multiparous mice differed in CRFR1-GFP levels relative to nulliparous mice. Together, these findings indicate dynamic changes in CRFR1 with multiparity that may contribute to stress-related behavior changes.

促肾上腺皮质激素释放因子（CRF）通过其主要受体（CRFR1）调控各种应激相关行为和神经内分泌反应。CRFR1也是啮齿动物产后应激相关行为变化的关键调节因子。先前的研究表明，在产后第一个时期，CRFR1在大脑各区域的动态变化，包括下丘脑催产素神经元中CRFR1表达的出现。我们试图确定这些CRFR1和CRFR1/催产素共表达的变化是如何随着重复的繁殖周期而改变的，以及这些神经适应是否与母性行为的变化相一致，这些变化发生在母性经验丰富的啮齿动物中。CRFR1-GFP报告小鼠繁殖1窝（初产）或3窝（多产），并在非应激和应激（雄性入侵者）条件下评估幼鼠的回收情况。收集未产、初产和多产小鼠的大脑，评估CRFR1- gfp以及CRFR1与催产素的共表达。在初产和多产小鼠之间，虽然在雄性入侵者暴露后，两组小鼠都表现出更大的徘徊潜伏期，但在幼仔检索方面没有统计学上的显著变化。然而，与初产和未产小鼠相比，多胎小鼠在室旁下丘脑（PVN）和视上核（SON）中的催产素/CRFR1共表达增加。与初产小鼠相比，多胎小鼠PVN和SON中的CRFR1-GFP也有所升高。在内侧视前区和腹侧脑室周围核中，初产小鼠与未产小鼠相比，CRFR1-GFP水平不同。总之，这些发现表明多胎CRFR1的动态变化可能有助于压力相关的行为改变。

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引用次数: 0

Birth controlling your fears: The long-term effects of adolescent exposure to hormonal contraceptives on fear extinction in long-evans female rats 生育控制你的恐惧：在long-evans雌性大鼠中，青春期接触激素避孕药对恐惧消退的长期影响

IF 2.5 3区医学 Q2 BEHAVIORAL SCIENCES

Hormones and Behavior

Pub Date : 2025-07-28 DOI: 10.1016/j.yhbeh.2025.105789

Madison Brooke , Bronwyn M. Graham

The mechanisms involved in inhibiting fear to a threatening cue can be studied in the laboratory via fear extinction, which is a process thought to underpin the development and treatment of anxiety disorders. In adult female rats, fluctuating sex hormones across the estrous cycle modulate fear extinction, and suppressing sex hormones via hormonal contraceptives (HCs) impairs fear extinction. Despite high usage of HCs during adolescence, no research has examined HC effects on extinction during this developmental phase. In the current study, adolescent female rats (postnatal day 35) were administered a nine day treatment of one of two HC formulations: a high dose of levonorgestrel (LEV), or a lower dose of LEV combined with ethinyl estradiol (EE). Rats received fear conditioning, extinction training, and extinction retention, either across the last few days of HC exposure, or two weeks post HC-cessation as adults (postnatal day 58). In both adolescents and adults, LEV impaired extinction retention, but EE + LEV did not. Altogether, these findings provide evidence that LEV impairs extinction retention during adolescence, and that this impairing effect lasts beyond the cessation of LEV when exposure begins during adolescence. Both HC formulations suppressed endogenous sex hormones during HC exposure, and neither produced long-term effects on endogenous sex hormones two weeks post cessation, suggesting that suppression of endogenous hormones were not the sole mechanism for the impairing effects of LEV on extinction retention. Such findings may have implications for the potential impact of HC use during adolescence on the development and treatment of anxiety disorders.

抑制对威胁线索的恐惧的机制可以通过恐惧消退在实验室中进行研究，这一过程被认为是焦虑症发展和治疗的基础。在成年雌性大鼠中，在发情周期中波动的性激素调节恐惧消退，而通过激素避孕药（HCs）抑制性激素会损害恐惧消退。尽管青少年时期HC的使用率很高，但没有研究调查过在这一发育阶段HC对灭绝的影响。在目前的研究中，青春期雌性大鼠（出生后第35天）接受为期9天的两种HC制剂中的一种治疗：高剂量的左炔诺孕酮（LEV），或低剂量的LEV与乙炔雌二醇（EE）联合。大鼠在HC暴露的最后几天或成年后HC停止后两周（出生后第58天）接受恐惧条件反射、消失训练和消失保留。在青少年和成人中，LEV都损害了消失保留，但EE + LEV没有。总之，这些发现提供了证据，表明LEV损害了青春期的消退保留，并且这种损害效应持续到青春期开始接触LEV时停止后。两种HC配方在HC暴露期间均抑制内源性性激素，并且在停止后两周均未对内源性性激素产生长期影响，这表明抑制内源性性激素并不是LEV损害灭绝保留作用的唯一机制。这些发现可能暗示了青少年时期使用HC对焦虑症的发展和治疗的潜在影响。

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引用次数: 0

A survey of hypothalamic phenotypes identifies molecular and behavioral consequences of MYT1L haploinsufficiency in male and female mice 一项下丘脑表型调查确定了雄性和雌性小鼠MYT1L单倍性不足的分子和行为后果

IF 2.5 3区医学 Q2 BEHAVIORAL SCIENCES

Hormones and Behavior

Pub Date : 2025-07-28 DOI: 10.1016/j.yhbeh.2025.105796

Susan E. Maloney , Katherine B. McCullough , Sneha M. Chaturvedi , Din Selmanovic , Rebecca Chase , Jiayang Chen , Shanyun Wu , Jorge L. Granadillo , Kristen L. Kroll , Joseph D. Dougherty

The transcription factor MYT1L supports proper neuronal differentiation and maturation during brain development. MYT1L haploinsufficiency results in a neurodevelopmental disorder characterized by intellectual disability, developmental delay, autism, behavioral disruptions, aggression, obesity and epilepsy. While MYT1L is expressed throughout the brain, how it supports proper neuronal function in distinct regions has not been assessed. Some features of MYT1L Neurodevelopmental Syndrome suggest disruption of hypothalamic function, such as obesity and endocrine issues, and previous research showed changes in hypothalamic neuropeptide expression following knockdown in zebrafish. Here, we leveraged our heterozygous Myt1l mutant, previously shown to recapitulate aspects of the human syndrome such as hyperactivity, social challenges, and obesity, to examine the impact of MYT1L loss on hypothalamic function. Examining the molecular profile of the MYT1L haploinsufficient hypothalamus revealed a similar scale of disruption to previously studied brain regions, yet with region-specific roles for MYT1L, including regulation of neuropeptide systems. Alterations in oxytocin and arginine vasopressin cell numbers were also found. Behaviors studied included maternal care, social group hierarchies, and aggression, all of which were unchanged. Feeding and metabolic markers were also largely unchanged in MYT1L haploinsufficient mice, yet an interaction was observed between diet and MYT1L genotype on weight gain. Our findings here suggest that gross endocrine function was not altered by MYT1L haploinsufficiency, and that key sex-specific behaviors related to proper hypothalamic function remain intact. Further study is needed to understand the functional impact of the altered hypothalamic molecular profile and changes in neuropeptide cell numbers that result from MYT1L haploinsufficiency.

转录因子MYT1L在大脑发育过程中支持适当的神经元分化和成熟。MYT1L单倍体功能不全导致以智力残疾、发育迟缓、自闭症、行为中断、攻击、肥胖和癫痫为特征的神经发育障碍。虽然MYT1L在整个大脑中表达，但它如何在不同区域支持适当的神经元功能尚未得到评估。MYT1L神经发育综合征的一些特征提示下丘脑功能的破坏，如肥胖和内分泌问题，先前的研究表明，在斑马鱼中敲除后下丘脑神经肽的表达发生了变化。在这里，我们利用我们的杂合Myt1l突变体，先前显示概括了人类综合征的各个方面，如多动、社交挑战和肥胖，来研究Myt1l丢失对下丘脑功能的影响。检查MYT1L单倍体不足下丘脑的分子图谱揭示了与先前研究的大脑区域相似的破坏规模，但MYT1L具有区域特异性作用，包括神经肽系统的调节。催产素和精氨酸抗利尿激素细胞数量的变化也被发现。研究的行为包括母性照顾、社会群体等级和攻击性，所有这些都没有变化。在MYT1L单倍型不足的小鼠中，喂养和代谢标志物也基本不变，但观察到饮食和MYT1L基因型对体重增加有相互作用。我们的研究结果表明，总内分泌功能不会因MYT1L单倍功能不全而改变，与下丘脑正常功能相关的关键性别特异性行为保持不变。MYT1L单倍体功能不全对下丘脑分子谱改变和神经肽细胞数量变化的功能影响尚需进一步研究。

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引用次数: 0

Sex difference in the effects of ventral pallidum vasopressin 1a receptor partial knockdown on social behavior in mice 小鼠腹侧白质抗利尿激素1a受体部分敲除对社会行为影响的性别差异

IF 2.5 3区医学 Q2 BEHAVIORAL SCIENCES

Hormones and Behavior

Pub Date : 2025-07-26 DOI: 10.1016/j.yhbeh.2025.105792

Caitlin N. Friesen , Delenn Hartswick , Alexandra Selke , Geert J. de Vries , Aras Petrulis

The neuropeptide vasopressin (AVP) regulates a diverse array of social behaviors, often having different functions in males and females. This sex difference is due, in part, to the AVP cells in the bed nucleus of the stria terminalis (BNST), which are more numerous in males than in females. These AVP cells send stronger projections to several brain regions that express the vasopressin 1a receptor (V1aR), including the ventral pallidum (vPal), an area broadly implicated in reward-seeking behavior. Previous experiments manipulating V1aR in vPal have found that activation of V1aR in this area mediates AVP effects on social behavior with differential effects on male and female rats across different social contexts. Consequently, to better understand the role of V1aR in vPal, we reduced V1aR expression in the vPal using a viral-mediated RNA-interference approach in male and female mice and tested their social investigatory, aggressive, copulatory and communicative responses to male and female conspecifics as well as their responses to anxiogenic or rewarding stimuli. Partial knockdown of V1aR in vPal of males reduced their social investigation of other males, but not of females, whereas the same manipulation had no effect on social investigation in females. In addition, partial knockdown in males reduced latencies to ejaculate during copulation. Reduction in V1aR within vPal did not influence communicative and aggressive behaviors, urine investigation, anxiety-like behavior, or sucrose preference. These results suggest that V1aR activity in the vPal specifically facilitates intermale investigation in adult mice but normally dampens their ejaculatory behavior.

神经肽抗利尿激素（AVP）调节各种各样的社会行为，通常在男性和女性中具有不同的功能。这种性别差异部分是由于终纹床核（BNST）中的AVP细胞，雄性比雌性多。这些AVP细胞向几个表达抗利尿激素1a受体（V1aR）的大脑区域发送更强的投射，包括腹侧苍白球（vPal），这是一个广泛涉及寻求奖励行为的区域。先前操纵vPal区V1aR的实验发现，该区域V1aR的激活介导了AVP对社会行为的影响，在不同的社会背景下，雄性和雌性大鼠的影响有所不同。因此，为了更好地理解V1aR在vPal中的作用，我们使用病毒介导的rna干扰方法降低了雄性和雌性小鼠vPal中V1aR的表达，并测试了它们对雄性和雌性同种动物的社会调查、攻击、交配和交流反应，以及它们对焦虑或奖励刺激的反应。男性vPal中V1aR的部分下调会降低其对其他男性的社会调查，但对女性没有影响，而同样的操作对女性的社会调查没有影响。此外，雄性基因的部分敲除减少了交配过程中射精的潜伏期。vPal中V1aR的降低不影响交流和攻击行为、尿液调查、焦虑样行为或蔗糖偏好。这些结果表明，vPal中的V1aR活性特别促进了成年小鼠的雄性间调查，但通常会抑制它们的射精行为。

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引用次数: 0

Chronic periadolescent leuprolide exposure affects the expression of multiple genes in the hypothalamus and pituitary gland with a different pattern of expression in female and male Long-Evans rats 长期暴露于青春期前后的leuprolide会影响雌性和雄性Long-Evans大鼠下丘脑和垂体中多种基因的表达，且表达模式不同

IF 2.5 3区医学 Q2 BEHAVIORAL SCIENCES

Hormones and Behavior

Pub Date : 2025-07-24 DOI: 10.1016/j.yhbeh.2025.105798

Fay A. Guarraci , Ian M. Klepcyk , Lindsay M. Thompson , Madeline Streifer , Emily N. Hilz , Grace Hudson , Sarah H. Meerts , Andrea C. Gore

Protracted exposure to drugs like Lupron Depot® suppresses pubertal development. How the brain responds and develops in the face of pharmacological suppression is not well understood. The present study tested the effects of daily leuprolide acetate (LEU) treatment (50 μg/kg, postnatal day (PD) 25–50) on gene expression (Kiss1, Esr1, Esr2, Ar, Gnrh1, Gnrhr) in the hypothalamus and pituitary of female and male Long-Evans rats using real-time PCR. Brains and trunk blood were harvested on PD 50. In the pituitary gland of both sexes, expression of Esr2 and Gnrhr expression was higher in LEU-treated rats than in saline controls. Esr1 expression in females was lower and Ar expression in males was higher in LEU-treated rats than saline controls. In the preoptic area of the hypothalamus in male rats, Kiss1 expression was significantly lower in LEU than in saline controls. In the mediobasal hypothalamus, Gnrh1 and Kiss1 expression was higher in LEU-treated male rats than in saline controls; for females, only Kiss1 was increased by LEU. Serum gonadal hormone levels were not significantly different in LEU-treated rats than saline controls at the end of treatment, although hormones trended lower in the LEU-treated rats. LEU affected expression of genes involved in reproduction, potentially explaining sex-specific effects of LEU on behavior reported earlier. The changes in hypothalamic and pituitary gene expression may represent compensation that permits early stages of pubertal development (e.g., VO and PPS), but not complete maturation (e.g., estrous cyclicity, sexual behavior) during LEU treatment.

长期暴露于像Lupron Depot®这样的药物会抑制青春期发育。面对药物抑制，大脑如何反应和发育尚不清楚。本研究采用实时荧光定量PCR技术检测了每天给药（50 μg/kg，产后（PD） 25-50天）醋酸LEU （LEU）对雌性和雄性Long-Evans大鼠下丘脑和垂体基因（Kiss1、Esr1、Esr2、Ar、Gnrh1、Gnrhr）表达的影响。PD 50采集了大脑和躯干血液。在两性垂体中，leu处理大鼠的Esr2和Gnrhr表达高于生理盐水对照组。与生理盐水对照组相比，leu处理的大鼠中雌性的Esr1表达较低，雄性的Ar表达较高。在雄性大鼠下丘脑视前区，Kiss1在LEU中的表达明显低于生理盐水对照组。在下丘脑中基底区，低leu处理的雄性大鼠Gnrh1和Kiss1的表达高于生理盐水对照组；在治疗结束时，低LEU处理的大鼠血清性腺激素水平与生理盐水对照组相比没有显著差异，尽管低LEU处理的大鼠血清性腺激素水平呈下降趋势。低LEU影响生殖相关基因的表达，这可能解释了之前报道的低LEU对行为的性别特异性影响。下丘脑和垂体基因表达的变化可能代表了在LEU治疗期间允许早期青春期发育（例如，VO和PPS），但不完全成熟（例如，发情周期，性行为）的补偿。

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引用次数: 0

A dopamine agonist affects the social decision-making of calling male túngara frogs 多巴胺激动剂影响雄性túngara蛙的社会决策

IF 2.5 3区医学 Q2 BEHAVIORAL SCIENCES

Hormones and Behavior

Pub Date : 2025-07-23 DOI: 10.1016/j.yhbeh.2025.105797

Logan S. James , Sarah C. Woolley , Michael J. Ryan

When vocalizing, many animals engage in decision-making processes that integrate information regarding the current social context. The midbrain dopaminergic system may provide a conserved mechanism underlying this process. For instance, in songbirds, modulation of dopamine release appears to contribute to social context-dependent changes to song. However, relatively little is known about the degree to which dopamine may contribute to similar vocal production and decision-making processes in other taxa, particularly the highly vocal anurans (frogs and toads). Here, we treated wild-caught male túngara frogs (Engystomops pustulosus) with a general dopamine agonist (apomorphine) and assessed its effects on motor performance and motivation as well as vocal decision-making in response to auditory stimuli that varied in social relevance. We found that the dopamine agonist generally increased vocal speed, with decreases in response latencies and call durations. Additionally, we found that dopamine increased call complexity, but only in response to the most socially relevant auditory stimulus (conspecific call). Finally, dopamine treatment and auditory stimulus interacted to affect decision-making regarding call timing and overlap with the stimulus. Compared to controls, frogs with apomorphine were more likely to overlap the playback stimulus in a manner predicted to be more attractive to females. These results highlight a role of dopaminergic circuits in modulating vocal outputs based on social inputs within a species of basal tetrapod.

当发声时，许多动物参与决策过程，整合有关当前社会背景的信息。中脑多巴胺能系统可能为这一过程提供了一个保守的机制。例如，在鸣禽中，多巴胺释放的调节似乎有助于社会环境对歌曲的依赖变化。然而，对于多巴胺在其他类群中对类似的发声和决策过程的贡献程度，特别是在发声能力强的无脊椎动物（青蛙和蟾蜍）中，我们所知相对较少。在这里，我们用一种通用的多巴胺激动剂（阿波啡）治疗野生雄性túngara青蛙（Engystomops pustlosus），并评估其对运动表现和动机的影响，以及对社会相关性不同的听觉刺激的声音决策的影响。我们发现多巴胺激动剂通常会增加声音速度，减少反应延迟和呼叫持续时间。此外，我们发现多巴胺增加了呼叫复杂性，但仅在对最具社会相关性的听觉刺激（同向呼叫）做出反应时才会增加。最后，多巴胺治疗和听觉刺激相互作用，影响呼叫时间和与刺激重叠的决策。与对照组相比，服用阿波啡的青蛙更有可能以一种预测对雌性更具吸引力的方式重复播放刺激。这些结果突出了多巴胺能回路在调节基于社会输入的声音输出中的作用。

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引用次数: 0

Hormonal and sex-specific functional genomic pathways of genetic risk candidates in autism spectrum disorder: evidence of sex-over-chance effects 自闭症谱系障碍遗传风险候选者的激素和性别特异性功能基因组途径：性别机会效应的证据

IF 2.5 3区医学 Q2 BEHAVIORAL SCIENCES

Hormones and Behavior

Pub Date : 2025-07-23 DOI: 10.1016/j.yhbeh.2025.105795

Camilo Briones-Valdivieso , Francisco Córdova , Heidy Kaune , Juan F. Montiel

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition marked by substantial sex differences in prevalence, with males more frequently diagnosed than females. While genetic and environmental factors contribute to ASD, there is growing evidence that sex-specific endocrine pathways, particularly those involving sex hormones, may play a critical role in ASD etiology. This study aimed to investigate the functional network robustness and annotations of autism spectrum disorder genetic risk candidates (ASD-GRCs), with a focus on endocrine pathways and their impact on network connectivity. Using data from the Simon's Foundation Autism Research Initiative (SFARI) and functional network analysis via the STRING database, we assessed the connectivity of ASD-related genes by randomly subtracting sets of genes from the whole ASD gene network in subsets associated with androgen-testosterone, estrogen-progesterone, and other hormone pathways.

Our findings reveal a significant “sex-over-chance” association, with androgen- and estrogen-related gene subsets showing marked connectivity within the ASD gene network compared to non-sex hormone genes. These results suggest that sex hormones may uniquely influence ASD-related neural development, providing support for the “female protective effect” and the androgen-driven model of ASD. Additional analyses of other hormonal pathways, such as oxytocin and cortisol, showed a lower connectivity impact, reinforcing the distinctive role of sex hormones in ASD. This study highlights the potential of endocrine-focused genetic analysis in understanding ASD, emphasizing sex-specific biological mechanisms that may inform future diagnostic and therapeutic strategies.

自闭症谱系障碍（ASD）是一种复杂的神经发育疾病，其患病率存在显著的性别差异，男性比女性更常被诊断出来。虽然遗传和环境因素会导致ASD，但越来越多的证据表明，性别特异性内分泌途径，特别是涉及性激素的内分泌途径，可能在ASD病因学中发挥关键作用。本研究旨在研究自闭症谱系障碍遗传风险候选者（autism spectrum disorder genetic risk candidate, ASD-GRCs）的功能网络鲁棒性和注释，重点关注内分泌通路及其对网络连接的影响。利用西蒙基金会自闭症研究计划（SFARI）的数据和通过STRING数据库进行的功能网络分析，我们通过从整个ASD基因网络中随机减去与雄激素-睾酮、雌激素-孕酮和其他激素通路相关的亚群的基因集来评估ASD相关基因的连通性。与非性激素基因相比，我们的研究结果揭示了一种显著的“性别过度”关联，与雄激素和雌激素相关的基因亚群在ASD基因网络中显示出显著的连通性。这些结果表明性激素可能是影响ASD相关神经发育的唯一因素，为“女性保护效应”和雄激素驱动的ASD模型提供了支持。对其他激素通路（如催产素和皮质醇）的进一步分析显示，其连通性影响较低，这加强了性激素在ASD中的独特作用。这项研究强调了以内分泌为中心的遗传分析在理解ASD方面的潜力，强调了性别特异性的生物学机制，可能为未来的诊断和治疗策略提供信息。

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引用次数: 0

Mineralocorticoid receptor deletion alters spontaneous behavior in an automated home-cage monitoring apparatus 矿化皮质激素受体缺失改变了自动家庭笼监测装置中的自发行为

IF 2.5 3区医学 Q2 BEHAVIORAL SCIENCES

Hormones and Behavior

Pub Date : 2025-07-21 DOI: 10.1016/j.yhbeh.2025.105794

Dalisa R. Kendricks , Sarah Jo Sleiman , Sydney A. Fry , Jariatu Stallone , Briana J. Bernstein , Korey D. Stevanovic , Leslie R. Aksu , Georgia M. Alexander , Katharine E. McCann , Serena M. Dudek , Jesse D. Cushman

Mineralocorticoid receptors (MRs) are transcription factors expressed throughout the body and brain, with especially high expression in the hippocampal area CA2. MRs are essential for maintaining the physiological stress response and regulating the hypothalamic-pituitary adrenal (HPA) axis. Further, MRs function through the diurnal modulation of corticosterone activity. The aim of the current study was to determine the role MRs play in the modulation of spontaneous behavior throughout the day/night cycle. Three conditional MR knockout mouse lines were utilized: one with broad embryonic neuronal deletion (Nestin-Cre), one with embryonic forebrain deletion (EMX-Cre), and one with postnatal CA2-targeted deletion (Amigo2-Cre). Behavior in these strains was assessed using an automated home cage monitoring system to track spontaneous behavior over a 60-h period. Broad deletion of MRs disrupted behavior in a sex-dependent manner, with alteration in motor activity and shelter behavior at night. Forebrain deletion of MRs produced similar, but less pronounced, differences in motor activity and shelter behavior, while CA2-targeted deletion produced little alteration in behavior either during the day or at night. These findings provide evidence for the essential role of MRs in the regulation of behavior across the day/night cycle and shed a light on the role of MR development and expression on behavior.

矿盐皮质激素受体（MRs）是一种转录因子，在整个身体和大脑中表达，在海马区CA2中表达尤其高。MRs对于维持生理应激反应和调节下丘脑-垂体-肾上腺（HPA）轴至关重要。此外，MRs通过皮质酮活性的昼夜调节发挥功能。当前研究的目的是确定MRs在整个昼夜周期的自发行为调节中所起的作用。使用了三种条件MR敲除小鼠系：一种是广泛胚胎神经元缺失（nesting - cre），一种是胚胎前脑缺失（EMX-Cre），一种是出生后ca2靶向缺失（Amigo2-Cre）。这些菌株的行为采用自动化家庭笼监测系统进行评估，跟踪60小时内的自发行为。MRs的广泛缺失以性别依赖的方式破坏了行为，改变了夜间的运动活动和庇护行为。前脑MRs缺失在运动活动和庇护行为上产生类似但不太明显的差异，而ca2靶向缺失在白天和晚上的行为上几乎没有改变。这些发现为MR在昼夜循环中调节行为的重要作用提供了证据，并揭示了MR的发育和表达在行为中的作用。

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引用次数: 0

Spatial and verbal performance relate to the duration of combined oral contraceptive use but do not change during the pill-free interval 空间和语言表现与联合口服避孕药使用的持续时间有关，但在无药间隔期间没有变化

IF 2.5 3区医学 Q2 BEHAVIORAL SCIENCES

Hormones and Behavior

Pub Date : 2025-07-17 DOI: 10.1016/j.yhbeh.2025.105790

Isabel Noachtar, Belinda Pletzer

Background

Ovarian hormones and testosterone have been related to verbal and spatial processing. Oral contraceptives are taken by approximately 150 million women worldwide often for extended time periods. To date, the literature on long-term effects of COCs on cognition is sparse, and results and methodology are inconsistent.

Objectives

In this manuscript we examined whether verbal and spatial performance changed (i) during short-term hormonal withdrawal as during the monthly pill pause and (ii) related to the duration of COC-use. We assessed the moderating effects of progestin type (androgenicity) and task complexity.

Methods

180 participants (60 androgenic COC-users, 60 anti-androgenic COC-users and 60 non-users with a menstrual cycle) were tested once during their active pill phase/luteal phase and once during their pill pause/menses. We compared mental rotation, navigation and verbal fluency performance between the pill pause and active intake phase in COC users and assessed how the differences compared to fluctuations along the menstrual cycle in naturally cycling women.

Results

No differences between active pill intake and pill pause were found in mental rotation, navigation or verbal fluency in long-term users. Irrespective of COC-phase, androgenic COC-users demonstrated higher orientation accuracy compared to anti-androgenic COC-users and non-users. Longer pill duration was associated with better orientation accuracy and decreased phonemic word and switching production in COC-users independent of the pill's androgenicity.

Conclusion

The association of verbal and spatial performance to COC use duration in the absence of short-term changes during the pill-free interval may hint at cumulative effects of long-term COC-use on spatial and verbal processing.

研究背景：多巴胺激素和睾酮与语言和空间处理有关。全世界约有1.5亿妇女长期服用口服避孕药。迄今为止，关于COCs对认知的长期影响的文献很少，结果和方法也不一致。在这篇文章中，我们研究了语言和空间表现是否在短期激素停药期间发生变化(i)和（ii）与coc使用时间有关。我们评估了黄体酮类型（雄激素性）和任务复杂性的调节作用。方法180名受试者（60名雄激素coc服用者、60名抗雄激素coc服用者和60名有月经周期的非服用者）分别在药物活性期/黄体期和停药期/月经期进行一次检测。我们比较了COC服用者在服药暂停和主动服药阶段的心理旋转、导航和语言流畅性表现，并评估了与自然月经周期女性月经周期波动相比的差异。结果长期服用者在心理旋转、导航和语言流畅性方面，主动服药与停药无显著差异。无论coc处于哪个阶段，雄激素coc使用者比非雄激素coc使用者和非雄激素coc使用者表现出更高的定向精度。较长的服药时间与coc使用者更好的定向准确性和减少音位词和转换产生有关，而不依赖于避孕药的雄激素性。结论在无药间隔内无短期变化的情况下，语言和空间表现与COC使用时间的关系可能提示长期使用COC对空间和语言加工的累积效应。

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引用次数: 0