Pinyue Fu

Background: Oxytocin (OT) is a nonapeptide hormone produced in the hypothalamus, released into the brain and peripheral circulation, and plays a key role in social behavior. Recent studies indicate that complement component C4a is an OT-binding protein, which modulates plasma OT concentrations in mice. However, the role of C4a is unclear as to whether it contributes to consolation behavior. Methods: Social behavior, especially allogrooming, which is a form of empathy that depends on detecting the emotional states of others, was measured in wild-type or C4a/Slp knockout (Slp^−/−) male mice. Results: Observer mice of both genotypes exhibited comforting (allogrooming) behavior toward a cage-mate demonstrator during reunion after brief isolation of the demonstrator mice. When demonstrator mice experienced body restraint stress during isolation, the allogrooming behavior was significantly increased in both genotypes, with a markedly greater increase in Slp^−/− than in Slp^+/+ mice. Allogrooming behavior in observer Slp^−/− mice was significantly suppressed by an OT receptor antagonist. Furthermore, immunohistochemical analysis revealed that activation was significantly elevated in OT-positive hypothalamic neurons in observer Slp^−/− mice that interacted with stressed demonstrator mice. OT release from the isolated hypothalamus, stimulated via CD38 and TRPM2 channel activation, was greater in Slp^−/− mice than in Slp^+/+ mice. Conclusions: Our results highlight that the data are consistent with a potential role for C4a in modulating neural circuits, possibly via its peripheral action on OT bioavailability. Direct evidence for C4a’s action within the brain remains a hypothesis for future investigation, for example, via site-specific manipulations.

Autism spectrum disorder (ASD) is a congenital, lifelong neurodevelopmental disorder whose main symptom is impaired social communication and interaction. However, no drug can treat social deficits in patients with ASD, and treatments to alleviate social behavioral deficits are sorely needed. Here, we examined the effect of oral supplementation of maca (Lepidium meyenii) on social deficits of in utero-exposed valproic acid (VPA) mice, widely used as an ASD model. Although maca is widely consumed as a fertility enhancer and aphrodisiac, it possesses multiple beneficial activities. Additionally, it benefits learning and memory in experimental animal models. Therefore, the effect of maca supplementation on the social behavioral deficit of VPA mice was assessed using a social interaction test, a three-stage open field test, and a five-trial social memory test. The oral supplementation of maca attenuated social interaction behavior deficit and social memory impairment. The number of c-Fos-positive cells and the percentage of c-Fos-positive oxytocin neurons increased in supraoptic and paraventricular neurons of maca-treated VPA mice. These results reveal for the first time that maca is beneficial to social memory and that it restores social recognition impairments by augmenting the oxytocinergic neuronal pathways, which play an essential role in diverse social behaviors.