青年与中年雌雄大鼠下丘脑腹内侧核生长激素释放激素神经元反调节神经化学标志物基因表达的比较

IF 2.9 Q3 NEUROSCIENCES

IBRO Neuroscience Reports Pub Date : 2025-09-10 DOI:10.1016/j.ibneur.2025.09.002

Rami Shrestha, Subash Sapkota, Karen P. Briski

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引用次数: 0

摘要

衰老通过未知的机制损害葡萄糖的反调节功能。下丘脑腹内侧核/背内侧分裂（VMNdm）生长激素释放激素（Ghrh）神经元通过Ghrh调节的结构多样的共表达神经化学物质的放电来控制反向调节。目前的研究使用基因沉默和单细胞激光弹射-微解剖/多重qPCR工具来研究衰老是否会改变这些细胞群中共同产生的抗调节抑制（γ-氨基丁酸）或刺激（Ghrh、谷氨酸、一氧化氮）神经递质标记基因的eu和/或低血糖模式。数据显示，老年大鼠（即各性别的中年大鼠）的基础Ghrh mRNA减少，以及年龄特异性的Ghrh转录对雌性低血糖的反应。老年大鼠表现出Ghrh对谷氨酸脱羧酶67 （GAD67）和GAD65 mrna的抑制，雌性大鼠的抑制性增强。在中年雄性大鼠中，两种GAD转录物对低血糖（一种与年龄相关的反应丧失）都不耐受。在老年雌性动物中，低血糖刺激GAD65基因表达，与年轻成年动物中ghrh介导的抑制相反。Ghrh抑制谷氨酰胺酶（GLS） mRNA在中年大鼠的性别，如年轻的成年人。与年轻成年男性不同，老年男性对低血糖没有GLS转录反应；年龄较大的低血糖雌性动物表现出GLS mRNA的上调，与年轻动物的下调表达不同。衰老仅在女性中降低神经元一氧化氮合酶（nNOS）基因谱在中年大鼠中，不论性别，nNOS转录都因低血糖而增加，但Ghrh不反对，表明这种抑制性基调丧失。研究结果支持了这样一种观点，即到中年时，衰老可能会根据性别调整VMNdm Ghrh神经元向脑葡萄糖调节网络发出的多模态传递信号。进一步的研究是有理由的，以确定与年龄相关的共表达递质释放模式对两性反调节的影响。

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Comparison of ventromedial hypothalamic nucleus growth hormone-releasing hormone neuron counterregulatory neurochemical marker gene expression in young adult versus middle-aged male and female rats

Aging impairs glucose counterregulatory function by unknown mechanisms. Ventromedial hypothalamic nucleus/dorsomedial division (VMNdm) growth hormone-releasing hormone (Ghrh) neurons control counterregulation through Ghrh-modulated discharge of structurally diverse co-expressed neurochemicals. Current research used gene silencing and single-cell laser-catapult-microdissection/multiplex qPCR tools to investigate whether aging alters eu- and/or hypoglycemic patterns of co-produced counterregulatory-inhibiting (γ-aminobutyric acid) or -stimulating (Ghrh; glutamate; nitric oxide) neurotransmitter marker genes in this cell population. Data document basal Ghrh mRNA diminution in older, i.e., middle-aged rats of each sex and age-specific Ghrh transcriptional responses to hypoglycemia in females. Older rats showed Ghrh repression of glutamate decarboxylase₆₇ (GAD₆₇) and GAD₆₅ mRNAs, a gain of inhibitory tone in female. In middle-age male rats, both GAD transcripts were refractory to hypoglycemia, an age-related response loss. In older females, hypoglycemia stimulated GAD₆₅ gene expression, contrary to Ghrh-mediated repression in young adult animals. Ghrh suppressed glutaminase (GLS) mRNA in middle-aged rats of each sex, like young adults. Unlike young adult males, older males showed no GLS transcriptional response to hypoglycemia; older hypoglycemic females exhibited up-regulated GLS mRNA, differing from down-regulated expression in younger animals. Aging reduced neuronal nitric oxide synthase (nNOS) gene profiles in females only; nNOS transcription was increased by hypoglycemia in middle-aged rats irrespective of sex, but was unopposed by Ghrh, indicating loss of this inhibitory tone. Results bolster the notion that by midde-age, aging may adjust, according to sex, multi-modal transmitter signaling by VMNdm Ghrh neurons to the brain glucose-regulatory network. Further research is justified to ascertain consequences of aging-associated patterns of co-expressed transmitter release on counterregulation in each sex.

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