Tph2 deficiency leads to alterations in social adjustment and socio-affective communication in neonatal rats: no rescue effect of communal nesting

Wang, Tianhua; Gnade, Aaron L.; Homberg, Judith R.; Samina, Marta C.F.; Castro, Rogério C.R.; Kolk, Sharon M.; Alenina, Natalia; Bader, Michael; Dai, Jinye; Wöhr, Markus

Tph2 deficiency leads to alterations in social adjustment and socio-affective communication in neonatal rats: no rescue effect of communal nesting

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Item Type:	Article
Title:	Tph2 deficiency leads to alterations in social adjustment and socio-affective communication in neonatal rats: no rescue effect of communal nesting
Creators Name:	Wang, Tianhua, Gnade, Aaron L., Homberg, Judith R., Samina, Marta C.F., Castro, Rogério C.R., Kolk, Sharon M., Alenina, Natalia, Bader, Michael, Dai, Jinye and Wöhr, Markus
Abstract:	Deficiency of tryptophan hydroxylase 2 (TPH2), the rate-limiting enzyme for serotonin (5-hydroxytryptamine, 5-HT) synthesis in the brain, was repeatedly reported to cause impairments in socio-affective communication and maternal affiliation across species, including mice, rats, and monkeys. We recently applied a rescue protocol in the Tph2 knockout rat model and demonstrated that communal nesting ameliorates maternal affiliation impairments. Interestingly, however, this rescue strategy did not lead to improvements in socio-affective communication and was associated with an aggravated growth retardation phenotype in Tph2-deficient offspring. In the present study, we aimed to gain deeper insight into the interplay between socio-affective communication, nesting condition, and test context. To this aim, we studied Tph2(−/−) knockout, Tph2(+/−) heterozygous, and Tph2(+/+) wildtype rat pups of both sexes, randomly assigned to standard versus communal nesting. We performed detailed spectrographic analyses and compared the emission of isolation-induced ultrasonic vocalizations under social test conditions, i.e., the maternal preference test and the homing test, to non-social test conditions, i.e., the isolation box test. Our results show that Tph2 deficiency causes prominent alterations in isolation-induced ultrasonic calling linked to reduced maternal responsiveness, including changes in acoustic features, e.g., increased call duration but reduced frequency modulation. Remarkably, irrespective of communal nesting, Tph2(−/−) pups typically displayed either no evidence for social adjustment or even changes opposite to Tph2(+/+) littermates, suggesting a reduction and/or delay in the capability and/or motivation to appropriately adjust to changes in the social environment. Such alterations in social adjustment likely contribute to growth retardation through reduced quality of mother-pup interactions.
Keywords:	Serotonin, Tryptophan Hydroxylase 2, Autism, Social Behavior, Ultrasonic Vocalizations, Animals, Rats
Source:	Progress in Neuro-Psychopharmacology & Biological Psychiatry
ISSN:	0278-5846
Publisher:	Elsevier
Volume:	141
Page Range:	111469
Date:	30 August 2025
Official Publication:	https://doi.org/10.1016/j.pnpbp.2025.111469
PubMed:	View item in PubMed

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