近日，来自美国西北大学的研究人员在对参与学习记忆和应激应答的脑部区域进行研究之后发现雄性和雌性的脑在分子水平上存在着不同的运作方式。相关研究结果发表在国际学术期刊journal of neuroscience上。
许多脑紊乱疾病的发生都在不同性别之间存在差异，但其中隐含的生物学过程是如何促进这些差异的产生仍然是一个迷。来自西北大学的神经科学家们发现雄性和雌性在对下丘脑部神经突触的分子调节上存在本质区别。
研究人员指出，研究两性之间脑部差异的重要性在于能够根据性别开发不同的治疗药物，而非用于解释谁更会看地图或者为什么在一些特定职业领域男性会多于女性。
在这项研究中，研究人员发现一种叫做URB-597的调节一种重要神经递质释放的药物对雌性有作用而对雄性没有作用。他们发现URB-597能够增加雌性大鼠脑部一种关键内源性大麻素--anandamide的抑制性作用，引起神经递质释放减少，而在雄性大鼠脑部没有这种作用。
内源性大麻素分子参与许多生理学过程，如记忆，食欲，疼痛以及癫痫的发生，是体内一类非常重要的分子。了解内源性大麻素的合成，释放和降解过程对于理解正常脑功能以及病理性脑功能异常都有广泛提示。
研究人员指出，虽然这项工作是以大鼠为实验模型完成的，但由于这种药物和其他类似药物正处于临床验证阶段，可能许多研究内元素大麻素的科学家仍然不知道对这些分子的调控还存在性别差异，因此对于人类研究也具有重要提示。
Sex Differences in Molecular Signaling at Inhibitory Synapses in the Hippocampus
Nino Tabatadze, Guangzhe Huang, Renee M. May, Anant Jain, and Catherine S. Woolley
The possibility that mechanisms of synaptic modulation differ between males and females has far-reaching implications for understanding brain disorders that vary between the sexes. We found recently that 17β-estradiol (E2) acutely suppresses GABAergic inhibition in the hippocampus of female rats through a sex-specific estrogen receptor α (ERα), mGluR, and endocannabinoid-dependent mechanism. Here, we define the intracellular signaling that links ERα, mGluRs, and endocannabinoids in females and identify wher in this pathway males and females differ. Using a combination of whole-cell patch-clamp recording and biochemical analyses in hippocampal slices from young adult rats, we show that E2 acutely suppresses inhibition in females through mGluR1 stimulation of phospholipase C, leading to inositol triphosphate (IP3) generation, activation of the IP3 receptor (IP3R), and postsynaptic endocannabinoid release, likely of anandamide. Analysis of sex differences in this pathway showed that E2 stimulates a much greater increase in IP3 levels in females than males, wheras the group I mGluR agonist DHPG increases IP3 levels equivalently in each sex. Coimmunoprecipitation showed that ERα-mGluR1 and mGluR1-IP3R complexes exist in both sexes but are regulated by E2 only in females. Independently of E2, a fatty acid amide hydrolase inhibitor, which blocks breakdown of anandamide, suppressed >50% of inhibitory synapses in females with no effect in males, indicating tonic endocannabinoid release in females that is absent in males. Together, these studies demonstrate sex differences in both E2-dependent and E2-independent regulation of the endocannabinoid system and suggest that manipulation of endocannabinoids in vivo could affect physiological and behavioral responses differently in each sex.