Palatable solution overconsumption in the Cntnap2-/- murine model of autism: a link with oxytocin.

IF 1.6 4区 医学 Q4 NEUROSCIENCES
Neuroreport Pub Date : 2024-10-16 Epub Date: 2024-08-07 DOI:10.1097/WNR.0000000000002089
Savannah Harvey, Donisha S N K Liyanagamage, Tapasya Pal, Anica Klockars, Allen S Levine, Pawel K Olszewski
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引用次数: 0

Abstract

Dysregulated appetite is common in autism spectrum disorder (ASD) and it includes excessive interest in tasty foods. Overconsumption of palatable fluids has been found in the valproic acid-induced ASD rat. Though ASD has a strong genetic component, the link between ASD-related genes and appetite for palatable foods remains elusive. We focused on the CNTNAP2 gene whose deletion in mice recapitulates human ASD symptoms. We investigated whether Cntnap2-/- male mice consume greater amounts of palatable 10% sucrose, 0.1% saccharin, and 4.1% intralipid solutions offered in episodic meals either in a no-choice paradigm or a two-bottle choice test. We examined how sucrose intake affects c-Fos immunoreactivity in feeding-related brain areas. Finally, we determined doses at which intraperitoneal oxytocin decreases sucrose intake in mutants. In the single-bottle tests, Cntnap2-/- mice drank more sucrose, saccharin, and intralipid compared to WTs. Given a choice between two tastants, Cntnap2-/- mice had a higher preference for sucrose than intralipid. While the standard 1 mg/kg oxytocin dose reduced sucrose intake in WTs, a low oxytocin dose (0.1 mg/kg) decreased sucrose intake in Cntnap2-/- mice. Sucrose intake induced a more robust c-Fos response in wild-type (WT) than Cntnap2-/- mice in the reward and hypothalamic sites and it increased the percentage of Fos-immunoreactivity oxytocin neurons in WTs, but not in mutants. We conclude that Cntnap2-/- mice overconsume palatable solutions, especially sucrose, beyond levels seen in WTs. This excessive consumption is associated with blunted c-Fos immunoreactivity in feeding-related brain sites, and it can be reversed by low-dose oxytocin.

Cntnap2-/-自闭症小鼠模型中美味溶液的过度摄入:与催产素有关。
食欲失调在自闭症谱系障碍(ASD)中很常见,包括对美味食物的过度兴趣。在丙戊酸诱导的自闭症谱系障碍大鼠身上发现了过度摄入适口液体的现象。虽然 ASD 有很强的遗传因素,但 ASD 相关基因与对美味食物的食欲之间的联系仍然难以捉摸。我们重点研究了 CNTNAP2 基因,该基因在小鼠体内的缺失可再现人类 ASD 症状。我们研究了在无选择范式或双瓶选择测试中,Cntnap2-/-雄性小鼠是否摄入了更多适口的 10%蔗糖、0.1% 糖精和 4.1% 脂内溶液。我们研究了蔗糖摄入如何影响进食相关脑区的 c-Fos 免疫反应。最后,我们确定了腹腔注射催产素降低突变体蔗糖摄入量的剂量。在单瓶测试中,与 WT 小鼠相比,Cntnap2-/- 小鼠喝了更多的蔗糖、糖精和内脂。在两种口味的选择中,Cntnap2-/-小鼠对蔗糖的偏好要高于内脂。标准的 1 毫克/千克催产素剂量会降低 WT 小鼠的蔗糖摄入量,而低催产素剂量(0.1 毫克/千克)会降低 Cntnap2-/-小鼠的蔗糖摄入量。与 Cntnap2-/-小鼠相比,野生型(WT)小鼠摄入蔗糖后在奖赏和下丘脑部位诱导的 c-Fos 反应更强,而且野生型小鼠 Fos 免疫反应催产素神经元的百分比有所增加,而突变体则没有。我们的结论是,Cntnap2-/-小鼠过度摄入适口溶液,尤其是蔗糖,超出了 WTs 的水平。这种过量摄入与摄食相关的大脑部位的 c-Fos 免疫反应性减弱有关,低剂量催产素可以逆转这种情况。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Neuroreport
Neuroreport 医学-神经科学
CiteScore
3.20
自引率
0.00%
发文量
150
审稿时长
1 months
期刊介绍: NeuroReport is a channel for rapid communication of new findings in neuroscience. It is a forum for the publication of short but complete reports of important studies that require very fast publication. Papers are accepted on the basis of the novelty of their finding, on their significance for neuroscience and on a clear need for rapid publication. Preliminary communications are not suitable for the Journal. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool. The core interest of the Journal is on studies that cast light on how the brain (and the whole of the nervous system) works. We aim to give authors a decision on their submission within 2-5 weeks, and all accepted articles appear in the next issue to press.
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