Liang Shu-Ling, Liao Wen-Lin, Chen Rou-Shayn
Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
J Neuroendocrinol. 2023 Apr;35(4):e13253. doi: 10.1111/jne.13253. Epub 2023 Mar 22.
Compared to male pups, perinatal female rats rely heavily on neuronal glutamine (Gln) transport for sustaining glutamatergic synaptic release in neurons of the ventrolateral ventral media nucleus of the hypothalamus (vlVMH). VMH mainly regulates female sexual behavior and increases glutamate release of perinatal hypothalamic neurons, permanently enhances dendrite spine numbers and is associated with brain and behavioral defeminization. We hypothesized that perinatal interruption of neuronal Gln transport may alter the glutamatergic synaptic transmission during adulthood. Perinatal rats of both sexes received an intracerebroventricular injection of a neuronal Gln uptake blocker, alpha-(methylamino) isobutyric acid (MeAIB, 5 mM), and were raised until adulthood. Whole-cell voltage-clamp recordings of miniature excitatory postsynaptic currents (mEPSCs) and evoked EPSCs (eEPSCs) of vlVMH neurons in adult rats with the perinatal pretreatment were conducted and neuron morphology was subjected to post hoc examination. Perinatal MeAIB treatment sex-differentially increased mEPSC frequency in males, but decreased mEPSC amplitude and synaptic Glu release in females. The pretreatment sex-differentially decreased eEPSC amplitude in males but increased AMPA/NMDA current ratio in females, and changed the morphology of vlVMH neurons of adult rats to that of the opposite sex. Most alterations in the glutamatergic synaptic transmission resembled the changes occurring during MeAIB acute exposure in perinatal rats of both sexes. We conclude that perinatal blockade of neuronal Gln transport mediates changes via different presynaptic and postsynaptic mechanisms to induce sex-differential alterations of the glutamatergic synaptic transmission and organization of vlVMH neurons in adult rats. These changes may be permanent and associated with brain and behavior feminization and/or defeminization in rats.
与雄性幼崽相比，围产期雌性大鼠严重依赖神经元谷氨酰胺（Gln）转运来维持下丘脑腹外侧腹内侧核（vlVMH）神经元中的谷氨酸能突触释放。VMH主要调节雌性性行为，并增加围产期下丘脑神经元的谷氨酸释放，永久性增加树突棘数量，并与大脑和行为的去雌性化有关。我们假设围产期神经元Gln转运的中断可能会改变成年期的谷氨酸能突触传递。对两性围产期大鼠进行脑室内注射神经元Gln摄取阻滞剂α-（甲基氨基）异丁酸（MeAIB，5 mM），并饲养至成年。对围产期预处理的成年大鼠vlVMH神经元进行微小兴奋性突触后电流（mEPSCs）和诱发EPSCs（eEPSCs）的全细胞电压钳记录，并对神经元形态进行事后检查。围产期MeAIB处理在雄性中性别差异地增加了mEPSC频率，但在雌性中降低了mEPSC幅度和突触谷氨酸释放。预处理在雄性中性别差异地降低了eEPSC幅度，但在雌性中增加了AMPA/NMDA电流比，并将成年大鼠vlVMH神经元的形态改变为异性的形态。谷氨酸能突触传递的大多数改变类似于两性围产期大鼠MeAIB急性暴露期间发生的变化。我们得出结论，围产期神经元Gln转运的阻断通过不同的突触前和突触后机制介导变化，以诱导成年大鼠谷氨酸能突触传递和vlVMH神经元组织的性别差异改变。这些变化可能是永久性的，并与大鼠的大脑和行为雌性化和/或去雌性化有关。
