Investigating how the novel hormone kisspeptin modulates sexual and emotional brain processing in response to odour cues.

性心理障碍是由心理问题而不是生理问题引起的性功能障碍。它涉及几种疾病（包括阳痿和性欲减退），总共影响三分之一的人。这会对个人及其伴侣造成严重后果，影响生活质量和人际关系，并降低成功受孕的机会。在联合王国，用医学和心理疗法治疗性心理障碍的费用估计为每年3200万英镑。目前的医学治疗受到诸如心脏病和癌症风险增加等副作用的限制，而且与心理治疗的接触仍然很差。因此，了解人类大脑的性处理过程，以帮助开发更安全、更有效的治疗方法，这一需求尚未得到满足。大脑边缘系统是大脑中控制情绪和本能的区域，包括那些与性欲和生殖行为有关的情绪和本能。边缘系统与其他几个大脑中心相互作用，包括那些与生殖有关的中心，有趣的是，它还与处理气味的大脑区域相连。嗅觉通过信息素的作用支撑着许多重要的交配行为。信息素是一种释放到空气中的化学物质，当个体闻到它时，它会引起特定的行为。越来越多的证据表明，信息素会影响人类的行为，例如，男性闻到处于排卵期的女性穿的t恤，会发现这种气味比未处于排卵期的女性穿的t恤更具性吸引力。Kisspeptin是一种激素，给那些脑部有特殊变化的健康男性服用后，可以减少性厌恶和负面情绪。最近的研究表明，含有kisspeptin的神经纤维在嗅球（处理气味的大脑区域）、边缘系统和下丘脑（产生生殖激素的腺体）之间建立了联系。在动物中，kisspeptin与嗅觉和交配密切相关，例如，当雄性老鼠失去kisspeptin受体时，它们也失去了优先嗅出雌性伴侣的能力。此外，当雌性老鼠闻到雄性老鼠的气味时，它们大脑中的kisspeptin活性会增加。目前，kisspeptin、嗅觉和性行为之间的关系还没有在人类中得到探索。我设计了一个功能磁共振实验，利用香味和费洛蒙的气味来确定kisspeptin是如何影响健康男性的大脑反应的。与这一领域的专家一起工作，我已经收集了一些初步数据，这些数据表明，闻到女性的香味会刺激健康男性的大脑边缘区域。我的初步工作非常有希望，并证明了我建议使用的成像技术可以在闻到女性香味时检测到大脑感兴趣区域的激活。为了了解血液中的kisspeptin是如何在这些脑区发挥作用的，确定kisspeptin如何穿过血脑屏障进入大脑是很重要的。为了做到这一点，我的实验室在一小群老鼠身上产生了初步数据，表明随着时间的推移，kisspeptin在血液中在大脑中积累，这表明kisspeptin确实穿过了血脑屏障。我现在将使用专门的技术来确定kisspeptin是如何穿过血脑屏障的。这将有利于kisspeptin相关治疗的发展，这些治疗可以以不同的方式到达大脑。总的目标是利用我的研究结果来帮助开发更安全、更有效的治疗性心理障碍的方法。

Psychosexual dysfunction is caused by problems with sexual functioning due to a psychological rather than a physical problem. It involves several disorders (including impotence and reduced sexual desire) that collectively affect 1 in 3 people. There are severe consequences for individuals and their partners, impairing quality of life and interpersonal relationships as well as reducing chances for successful conception. In the UK the cost of treating psychosexual disorders with medical and psychological therapy is estimated at £32 million/year. Current medical treatments are limited by side-effects such as increased heart disease and cancer risk, and engagement with psychological therapies continues to be poor. Therefore, there is an unmet need to understand human sexual brain processing to help develop safer and more effective treatments. The limbic system is an area of the brain known to control emotions and instincts, including those related to sexual desire and reproductive behaviours. The limbic system interacts with several other brain centres including those involved in reproduction and interestingly, it also connects with brain areas that process smells. Smell underpins many important mating behaviours through the action of pheromones. Pheromones are chemicals that are released into the air and cause specific behaviours when smelled by an individual. There is growing evidence that pheromones affect human behaviour, for example men who smell t-shirts worn by women in their fertile phase, find that smell more sexually appealing compared to the smell of t-shirts from women who are not in their fertile phase. Kisspeptin is a hormone that reduces sexual aversion and negative mood when given to healthy men with specific brain changes seen on functional magnetic resonance imaging (fMRI). Recent work shows nerve fibres that contain kisspeptin make connections between the olfactory bulb (brain area processing smell), the limbic system and hypothalamus (a gland producing reproductive hormones). In animals, kisspeptin is closely linked with smell and mating e.g. when male mice lose their kisspeptin receptors, they also lose the ability to preferentially sniff out a female partner. Also, when female rats smell a male rat, they show increased kisspeptin activity in their brains. At present this relationship between kisspeptin, smell and sexual behaviour has not been explored in humans.I have designed an fMRI experiment using fragrance and pheromone smells to determine how kisspeptin affects brain response when these smells are presented to healthy men. Working alongside experts in this field, I have already collected pilot data which shows that smelling sexually arousing female fragrance activates limbic brain areas in healthy men. My preliminary work is very promising and demonstrates the imaging techniques I propose to use can detect activation in the brain areas of interest when smelling a female fragrance. To understand how kisspeptin in the bloodstream is able to carry out its actions on these brain areas, it is important to establish how kisspeptin gets across the blood-brain barrier into the brain. To do this, my laboratory has generated pilot data in a small group of mice showing that kisspeptin in the bloodstream builds up in the brain over time, which suggests that kisspeptin does cross the blood-brain barrier. I will now use specialised techniques to identify how kisspeptin moves across the blood-brain barrier. This will be beneficial for the development of kisspeptin-related treatments that can reach the brain in different ways. The overall aim is to use my results to help develop safer and more effective therapies for psychosexual disorders.