Brain-derived neurotrophic factor (BDNF) is known to play a critical role early in the development of cortical GABAergic interneurons. Recently our laboratory and others have shown protracted development of specific subpopulations of GABAergic interneurons extending into adolescence. BDNF expression also changes significantly across adolescent development. However the role of BDNF in regulating GABAergic changes across adolescence remains unclear. Here, we performed a week-by-week analysis of the protein expression and cell density of three major GABAergic interneurons, parvalbumin (PV), somatostatin (SST) and calretinin (Cal) in the medial prefrontal cortex from prepubescence (week 3) to adulthood (week 12). In order to assess how BDNF and sex might influence the adolescent trajectory of GABAergic interneurons we compared WT as well as BDNF heterozygous (+/−) male and female mice. In both males and females PV expression increases during adolescent development in the mPFC. Compared to wild-types, PV expression was reduced in male but not female BDNF+/− mice throughout adolescent development. This reduction in protein expression corresponded with reduced cell density, specifically within the infralimbic prefrontal cortex. SST expression increased in early adolescent WT females and this upregulation was delayed in BDNF+/−. SST cell density also increased in early adolescent mPFC of WT female mice, with BDNF+/− again showing a reduced pattern of expression. Cal protein expression was also sex-dependently altered across adolescence with WT males showing a steady decline but that of BDNF+/− remaining unaltered. Reduced cell density in on the other hand was observed particularly in male BDNF+/− mice. In females, Cal protein expression and cell density remained largely stable. Our results show that PV, SST and calretinin interneurons are indeed still developing into early adolescence in the mPFC and that BDNF plays a critical, sex-specific role in mediating expression and cell density.

已知脑源性神经营养因子（BDNF）在皮层GABA能性中间神经元的发育早期起关键作用。最近，我们的实验室和其他实验室已经证明，GABA能中间神经元的特定亚群的长期发育一直延伸到青春期。BDNF表达在整个青春期发育过程中也发生显着变化。然而，BDNF在调节青春期GABA能变化中的作用仍不清楚。在这里，我们进行了从青春期前（第3周）到前额叶内侧皮层中三个主要GABA能神经元，小白蛋白（PV），生长抑素（SST）和降钙素（Cal）的蛋白表达和细胞密度的每周分析。成年（第12周）。为了评估BDNF和性别如何影响GABA能中间神经元的青春期轨迹，我们比较了WT和BDNF杂合（+/-）雄性和雌性小鼠。在雄性和雌性中，mPFC的青春期发育过程中，PV表达均增加。与野生型相比，在整个青春期发育过程中，雄性BDNF +/-雌性小鼠的PV表达均降低，但不降低。蛋白质表达的这种降低对应于细胞密度的降低，特别是在下唇前额叶皮层内。在青春期早期的WT女性中，SST表达增加，而在BDNF +/-中，这种上调被延迟了。在WT雌性小鼠的青春期早期mPFC中，SST细胞密度也增加，而BDNF +/-再次显示出降低的表达模式。在整个青春期，Cal蛋白的表达也随性别而改变，WT男性表现出稳定的下降，而BDNF +/-则保持不变。另一方面，尤其在雄性BDNF +/-小鼠中观察到细胞密度降低。在雌性中，Cal蛋白表达和细胞密度基本保持稳定。我们的结果表明，PV，SST和降钙素中间神经元确实仍在mPFC中发展到青春期早期，而BDNF在介导表达和细胞密度方面起着至关重要的，性别特异性的作用。