Inhibiting Production of New Brain Cells during Puberty or Adulthood Blunts the Hormonally Induced Surge of Luteinizing Hormone in Female Rats.

Inhibiting Production of New Brain Cells during Puberty or Adulthood Blunts the Hormonally Induced Surge of Luteinizing Hormone in Female Rats.
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DOI:
10.1523/eneuro.0133-17.2017
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发表时间:
2017-09
期刊:
影响因子:
3.4
通讯作者:
Sisk CL
Sisk CL
中科院分区:
医学3区
文献类型:
--
作者:
Mohr MA;DonCarlos LL;Sisk CL

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在青春期和成年期,下丘脑区域会增加新的细胞,这些细胞控制着生殖、稳态和社会行为,但这些晚出生的细胞的功能仍然难以捉摸。在这里,我们研究了在青春期或成年期抑制心室区细胞增殖,并确定了随后对雌性大鼠黄体生成素(LH)激增的影响。最初的神经解剖学分析集中于验证下丘脑前腹侧室周核(AVPV)中青春期或成年出生细胞的掺入、激活和药理学抑制,因为AVPV在触发女性排卵前LH峰中起着重要作用。我们首先发现,大约一半的青春期出生的AVPV细胞被雌二醇加孕酮(P)处理激活,如Fos表达所示,大约10%的青春期出生的AVPV细胞表达雌激素受体α(ERα)。接下来,我们发现,无论是在青春期还是在成年期,通过侧脑室(ICV)给予胞嘧啶β-D-阿拉伯呋喃糖苷(AraC)抑制有丝分裂,都会减少AVPV和视交叉上核(SCN)中添加的新细胞数量,并且还会减弱和延迟垂体诱导的LH峰。这些研究并未证明,但高度暗示,产后室周脑区域(包括AVPV和SCN)中持续增加的新细胞可能对雌性生殖的完整性很重要。
New cells are added during both puberty and adulthood to hypothalamic regions that govern reproduction, homeostasis, and social behaviors, yet the functions of these late-born cells remain elusive. Here, we pharmacologically inhibited cell proliferation in ventricular zones during puberty or in adulthood and determined subsequent effects on the hormone-induced surge of luteinizing hormone (LH) in female rats. Initial neuroanatomical analyses focused on verifying incorporation, activation, and pharmacological inhibition of pubertally or adult born cells in the anteroventral periventricular nucleus (AVPV) of the hypothalamus because of the essential role of the AVPV in triggering the preovulatory LH surge in females. We first showed that approximately half of the pubertally born AVPV cells are activated by estradiol plus progesterone (P) treatment, as demonstrated by Fos expression, and that approximately 10% of pubertally born AVPV cells express estrogen receptor alpha (ERα). Next, we found that mitotic inhibition through intracerebroventricular (ICV) administration of cytosine β-D-arabinofuranoside (AraC), whether during puberty or in adulthood, decreased the number of new cells added to the AVPV and the suprachiasmatic nucleus (SCN), and also blunted and delayed the hormone-induced LH surge. These studies do not prove, but are highly suggestive, that ongoing postnatal addition of new cells in periventricular brain regions, including the AVPV and SCN, may be important to the integrity of female reproduction.