Carrillo Maria, Ricci Lesley A, Melloni Richard H
Behavioral Neuroscience Program, Department of Psychology, 125 Nightingale Hall, Northeastern University, 360 Huntington Avenue, Boston, MA 02155, USA.
Brain Res. 2009 Jan 16;1249:118-27. doi: 10.1016/j.brainres.2008.10.053. Epub 2008 Nov 5.
Chronic treatment with anabolic-androgenic steroids (AAS) during adolescence alters the activity of various neurotransmitter systems in male Syrian hamsters (Mesocricetus auratus). The present study was conducted to determine whether glutamatergic cells in the lateral anterior hypothalamus (LAH), a sub-region of the anterior hypothalamus, have lasting activation following adolescent AAS exposure, and to examine AAS-induced alterations in the connections between the LAH and the ventrolateral hypothalamus (VLH) governed by glutamate. Hamsters were administered AAS during adolescence and then examined for changes in FOS (protein product of the immediate early gene c-fos) and phosphate activated glutaminase (PAG; the rate-limiting enzyme in the synthesis of glutamate) immunoreactivity (FOS/PAG-IR) using double-label immunohistochemistry. In a second experiment, a retrograde tracing study was conducted using a red fluorescent tracer microinjected into the VLH. Then brains were processes for PAG immunofluorescence and examined for AAS-induced changes in the number of PAG positive cells containing the tracer (PAG/Tracer) in the LAH. When compared to oil-treated controls, AAS-treated hamsters showed significant increases in PAG-IR and FOS/PAG-IR in the LAH, decreases in afferent innervation from the LAH to the VLH and decreases in the total number of glutamate cells in the LAH projecting to the VLH. Together with previous research from our lab showing increased AAS-induced expression of PAG in the AH and increased glutamate receptor expression in the VLH, the current results suggest that adolescent AAS exposure leads to alterations in the function and expression of the glutamatergic system as well as changes in hypothalamic neural connections. In addition, the current results further strengthen the notion that a specific nucleus in the AH, the LAH is a critical hypothalamic sub-region particularly sensitive to AAS-induced neurodevelopmental effects.
青春期长期使用合成代谢雄激素类固醇（AAS）会改变雄性叙利亚仓鼠（金仓鼠）各种神经递质系统的活性。本研究旨在确定下丘脑前部的一个亚区域——外侧下丘脑前部（LAH）中的谷氨酸能细胞在青春期接触AAS后是否会持续激活，并研究AAS诱导的由谷氨酸介导的LAH与腹外侧下丘脑（VLH）之间连接的改变。在青春期给仓鼠施用AAS，然后使用双标免疫组织化学检查FOS（即刻早期基因c-fos的蛋白质产物）和磷酸激活谷氨酰胺酶（PAG；谷氨酸合成中的限速酶）免疫反应性（FOS/PAG-IR）的变化。在第二个实验中，使用微注射到VLH中的红色荧光示踪剂进行逆行追踪研究。然后对大脑进行PAG免疫荧光处理，并检查AAS诱导的LAH中含有示踪剂的PAG阳性细胞数量（PAG/示踪剂）的变化。与用油处理的对照组相比，接受AAS处理的仓鼠在LAH中的PAG-IR和FOS/PAG-IR显著增加，从LAH到VLH的传入神经支配减少，并且投射到VLH的LAH中谷氨酸能细胞总数减少。结合我们实验室之前的研究表明AAS诱导的AH中PAG表达增加以及VLH中谷氨酸受体表达增加，目前的结果表明青春期接触AAS会导致谷氨酸能系统的功能和表达改变以及下丘脑神经连接的变化。此外，目前的结果进一步强化了这样一种观念，即AH中的一个特定核团——LAH是一个对AAS诱导的神经发育效应特别敏感的关键下丘脑亚区域。
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