Faculty of Psychology, Experimental and Biological Psychology, Philipps-Universität Marburg, Behavioral Neuroscience, 35032, Marburg, Germany.
Philipps-Universität Marburg, Center for Mind, Brain, and Behavior (CMBB), 35032, Marburg, Germany.
Mol Autism. 2024 Nov 29;15(1):50. doi: 10.1186/s13229-024-00629-x.
A lack of serotonin (also known as 5-hydroxytryptamine, 5-HT) in the brain due to deficiency of the rate-limiting enzyme in 5-HT synthesis, tryptophan hydroxylase 2 (TPH2), was recently reported to result in impaired maternal affiliation across species, including mice, rats, and monkeys. In rodents, this was reflected in a lack of preference for maternal odors and reduced levels of isolation-induced ultrasonic vocalizations (USV), possibly contributing to a severe growth retardation phenotype.
Here, we tested whether growth retardation, maternal affiliation deficits, and/or impairments in socio-affective communication caused by Tph2 deficiency can be rescued through early social enrichment in rats. To this aim, we compared male and female Tph2 knockout and Tph2 heterozygous rat pups to Tph2 wildtype littermate controls, with litters being randomly assigned to standard nesting (SN; one mother with her litter) or communal nesting (CN; two mothers with their two litters).
Our results show that Tph2 deficiency causes severe growth retardation, together with moderate impairments in somatosensory reflexes and thermoregulatory capabilities, partially aggravated by CN. Tph2 deficiency further led to deficits in socio-affective communication, as evidenced by reduced emission of isolation-induced USV, associated with changes in acoustic features, clustering of subtypes, and temporal organization. Although CN did not rescue the impairments in socio-affective communication, CN ameliorated the maternal affiliation deficit caused by Tph2 deficiency in the homing test. To close the communicative loop between mother and pup, we assessed maternal preference and showed that mothers display a preference for Tph2 controls over Tph2 pups, particularly under CN conditions. This is consistent with the aggravated growth phenotype in Tph2 pups exposed to the more competitive CN environment.
Together, this indicates that CN aggravates growth retardation despite ameliorating maternal affiliation deficits in Tph2-deficient rat pups, possibly due to reduced and acoustically altered isolation-induced USV, hindering efficient socio-affective communication between mother and pup.
由于 5-羟色胺合成限速酶色氨酸羟化酶 2（TPH2）的缺乏，导致大脑中 5-羟色胺（也称为 5-羟色胺，5-HT）的缺乏，最近有报道称这会导致跨物种的母婴联系受损，包括老鼠、大鼠和猴子。在啮齿动物中，这表现为对母体气味缺乏偏好，以及隔离诱导的超声波发声（USV）水平降低，这可能导致严重的生长迟缓表型。
在这里，我们测试了 Tph2 缺乏是否可以通过大鼠早期社会丰容来挽救生长迟缓、母婴联系缺陷和/或社会情感交流障碍。为此，我们比较了 Tph2 敲除和 Tph2 杂合子雄性和雌性大鼠幼仔与 Tph2 野生型同窝仔对照，将幼仔随机分配到标准巢（SN；一只母鼠和她的幼仔）或共巢（CN；两只母鼠和她们的两个幼仔）。
我们的结果表明，Tph2 缺乏导致严重的生长迟缓，同时伴有中等程度的躯体感觉反射和体温调节能力受损，CN 部分加重。Tph2 缺乏进一步导致社会情感交流障碍，这表现为隔离诱导的 USV 减少，与声学特征变化、亚型聚类和时间组织有关。尽管 CN 没有挽救社会情感交流障碍，但 CN 改善了 Tph2 缺乏引起的归巢测试中的母婴联系缺陷。为了关闭母子之间的沟通循环，我们评估了母性偏好，并表明母亲更喜欢 Tph2 对照而不是 Tph2 幼仔，尤其是在 CN 条件下。这与 Tph2 幼仔在更具竞争力的 CN 环境中暴露时生长表型加重是一致的。
总的来说，这表明尽管 Tph2 缺乏的大鼠幼仔中的 CN 改善了母婴联系缺陷，但它加剧了生长迟缓，这可能是由于隔离诱导的 USV 减少和声学改变，阻碍了母子之间有效的社会情感交流。
