Hacohen Kleiman Gal, Barnea Anat, Gozes Illana
Department of Human Molecular Genetics and Biochemistry, Sackler Medical School, Adams Super Center for Brain Studies & Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel; Department of Natural and Life Sciences, The Open University, Raanana, Israel.
Department of Natural and Life Sciences, The Open University, Raanana, Israel.
Peptides. 2015 Oct;72:75-9. doi: 10.1016/j.peptides.2015.04.008. Epub 2015 Apr 17.
ADNP is a protein necessary for brain development, important for brain plasticity, cognitive and social functioning, characteristics that are all impaired in autism and in the Adnp(+/-) mouse model, in a sex-dependent manner. ADNP was originally discovered as a protein that is secreted from glial cells in response to vasoactive intestinal peptide (VIP). VIP is a major neuroprotective peptide in the CNS and PNS and was also associated with social recognition in rodents and aggression, pair-bonding and parental behaviors in birds. Comparative sequence alignment revealed high evolutionary conservation of ADNP in Chordata. Despite its importance in brain function, ADNP has never been studied in birds. Zebra finches (Taeniopygia guttata) are highly social songbirds that have a sexually dichotomous anatomical brain structure, with males demonstrating a developed song system, presenting a model to study behavior and potential sexually dependent fundamental differences. Here, using quantitative real time polymerase chain reaction (qRT-PCR), we discovered sexually dichotomous and age related differences in ADNP mRNA expression in three different regions of the song bird brain-cerebellum, cerebrum, and brain stem. Higher levels of ADNP mRNA were specifically found in young male compared to the female cerebrum, while aging caused a significant 2 and 3-fold decrease in the female and male cerebrum, respectively. Furthermore, a comparison between the three tested brain regions revealed unique sex-dependent ADNP mRNA distribution patterns, affected by aging. Future studies are aimed at deciphering the function of ADNP in birds, toward a better molecular understanding of sexual dichotomy in singing behavior in birds.
ADNP是大脑发育所必需的一种蛋白质，对大脑可塑性、认知和社交功能很重要，而这些特征在自闭症和Adnp(+/-)小鼠模型中均受到损害，且存在性别依赖性。ADNP最初是作为一种由神经胶质细胞响应血管活性肠肽（VIP）而分泌的蛋白质被发现的。VIP是中枢神经系统和外周神经系统中的一种主要神经保护肽，也与啮齿动物的社会认知以及鸟类的攻击、配对结合和育儿行为有关。比较序列比对显示ADNP在脊索动物中具有高度的进化保守性。尽管ADNP在脑功能中很重要，但从未在鸟类中进行过研究。斑胸草雀（Taeniopygia guttata）是高度社会化的鸣禽，具有两性异型的大脑解剖结构，雄性具有发达的鸣叫系统，为研究行为和潜在的性别依赖性根本差异提供了一个模型。在这里，我们使用定量实时聚合酶链反应（qRT-PCR），发现鸣禽大脑的三个不同区域——小脑、大脑和脑干中，ADNP mRNA表达存在性别差异和年龄相关差异。与雌性大脑相比，在年轻雄性大脑中特异性地发现了更高水平的ADNP mRNA，而衰老导致雌性和雄性大脑中的ADNP mRNA水平分别显著下降2倍和3倍。此外，对三个测试脑区的比较揭示了受衰老影响的独特的性别依赖性ADNP mRNA分布模式。未来的研究旨在破译ADNP在鸟类中的功能，以便更好地从分子层面理解鸟类鸣叫行为中的性别差异。
