Młotkowska Patrycja, Osuch Bartosz, Marciniak Elżbieta, Roszkowicz-Ostrowska Katarzyna, Misztal Tomasz
Department of Animal Physiology, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Instytucka 3 St., 05-110 Jablonna, Poland.
Int J Mol Sci. 2025 Oct 16;26(20):10062. doi: 10.3390/ijms262010062.
The hypothalamus is a key regulator of fundamental physiological processes and a site of adult neurogenesis. Allopregnanolone (ALLO) is a neurosteroid that mitigates the adverse effects of stress on the central nervous system and also affects neurogenesis. This study examined the effects of acute stress and ALLO administration (separately or in combination) into the third brain ventricle on the expression of neurotrophins and Trkβ receptor in distinct hypothalamic areas of sexually active female sheep. Expression of genes encoding brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4) and the Trkβ receptor was analyzed in the medial basal hypothalamus (MBH), arcuate nucleus (ARC), anterior hypothalamus (AHA), paraventricular nucleus (PVN), and preoptic area (POA). Acute stress stimulated the expression of neurotrophins (BDNF, NGF, and NT-3) in the ARC and PVN, while inhibitory effects predominated in the MBH, AHA and POA. ALLO alone mainly suppressed neurotrophins expression, while stimulatory effects were limited to the BDNF-Trkβ system in the ARC and Trkβ in the AHA. When combined with stress, ALLO either counteracted stress-induced increases in neurotrophins expression or produced no effect. The results demonstrate that acute stress can differentially modify neurotrophins mRNA expression in hypothalamic regions, activating neurotrophic activity in specific nuclei. The predominant inhibitory effect of ALLO on neurotrophin synthesis, particularly under conditions of acute stress, may help prevent excessive neuronal activation. Conversely, the upregulation of the BDNF-Trkβ system in the ARC indicates a positive relationship between this neurosteroid and hypothalamic adult neurogenesis.
下丘脑是基本生理过程的关键调节者，也是成体神经发生的场所。别孕烯醇酮（ALLO）是一种神经甾体，可减轻应激对中枢神经系统的不良影响，还会影响神经发生。本研究检测了向性活跃雌性绵羊的第三脑室单独或联合注射急性应激和ALLO，对下丘脑不同区域神经营养因子和Trkβ受体表达的影响。分析了内侧基底下丘脑（MBH）、弓状核（ARC）、下丘脑前部（AHA）、室旁核（PVN）和视前区（POA）中编码脑源性神经营养因子（BDNF）、神经生长因子（NGF）、神经营养因子-3（NT-3）、神经营养因子-4（NT-4）和Trkβ受体的基因表达。急性应激刺激了ARC和PVN中神经营养因子（BDNF、NGF和NT-3）的表达，而抑制作用在MBH、AHA和POA中占主导。单独使用ALLO主要抑制神经营养因子的表达，而刺激作用仅限于ARC中的BDNF-Trkβ系统和AHA中的Trkβ。与应激联合时，ALLO要么抵消应激诱导的神经营养因子表达增加，要么没有效果。结果表明，急性应激可差异调节下丘脑区域神经营养因子mRNA表达，激活特定核团的神经营养活性。ALLO对神经营养因子合成的主要抑制作用，特别是在急性应激条件下，可能有助于防止神经元过度激活。相反，ARC中BDNF-Trkβ系统的上调表明这种神经甾体与下丘脑成体神经发生之间存在正相关。
