Dataset Information

Altered gut microbiome and autism like behavior are associated with parental high salt diet in male mice.

ABSTRACT: Neurodevelopmental disorders are conditions caused by the abnormal development of the central nervous system. Autism spectrum disorder (ASD) is currently the most common form of such disorders, affecting 1% of the population worldwide. Despite its prevalence, the mechanisms underlying ASD are not fully known. Recent studies have suggested that the maternal gut microbiome can have profound effects on neurodevelopment. Considering that the gut microbial composition is modulated by diet, we tested the hypothesis that ASD-like behavior could be linked to maternal diet and its associated gut dysbiosis. Therefore, we used a mouse model of parental high salt diet (HSD), and specifically evaluated social and exploratory behaviors in their control-fed offspring. Using 16S genome sequencing of fecal samples, we first show that (1) as expected, HSD changed the maternal gut microbiome, and (2) this altered gut microbiome was shared with the offspring. More importantly, behavioral analysis of the offspring showed hyperactivity, increased repetitive behaviors, and impaired sociability in adult male mice from HSD-fed parents. Taken together, our data suggests that parental HSD consumption is strongly associated with offspring ASD-like behavioral abnormalities via changes in gut microbiome.

SUBMITTER: Afroz KF

PROVIDER: S-EPMC8052368 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Altered gut microbiome and autism like behavior are associated with parental high salt diet in male mice.

Afroz Kazi Farhana KF Reyes Noah N Young Kobe K Parikh Kajal K Misra Varsha V Alviña Karina K

Scientific reports 20210416 1

Neurodevelopmental disorders are conditions caused by the abnormal development of the central nervous system. Autism spectrum disorder (ASD) is currently the most common form of such disorders, affecting 1% of the population worldwide. Despite its prevalence, the mechanisms underlying ASD are not fully known. Recent studies have suggested that the maternal gut microbiome can have profound effects on neurodevelopment. Considering that the gut microbial composition is modulated by diet, we tested ...[more]

PMID: 33863940

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Project description:Parental care is critical for successful reproduction in mammals. Recent work has implicated the hormone prolactin in regulating male parental behavior, similar to its established role in females. Male laboratory mice show a mating-induced suppression of infanticide (normally observed in virgins) and onset of paternal behavior 2 weeks after mating. Using this model, we sought to investigate how prolactin acts in the forebrain to regulate paternal behavior. First, using c-fos immunoreactivity in prolactin receptor (Prlr) Prlr-IRES-Cre-tdtomato reporter mouse sires, we show that the circuitry activated during paternal interactions contains prolactin-responsive neurons in multiple sites, including the medial preoptic nucleus, bed nucleus of the stria terminalis, and medial amygdala. Next, we deleted Prlr from three prominent cell types found in these regions: glutamatergic, GABAergic, and CaMKIIα. Prlr deletion from CaMKIIα, but not glutamatergic or GABAergic cells, had a profound effect on paternal behavior as none of these KO males completed the pup-retrieval task. Prolactin was increased during mating, but not in response to pups, suggesting that the mating-induced secretion of prolactin is important for establishing the switch from infanticidal to paternal behavior. Pharmacological blockade of prolactin secretion at mating, however, had no effect on paternal behavior. In contrast, suppressing prolactin secretion at the time of pup exposure resulted in failure to retrieve pups, with exogenous prolactin administration rescuing this behavior. Together, our data show that paternal behavior in sires is dependent on basal levels of circulating prolactin acting at the time of interaction with pups, mediated through Prlr on CaMKIIα-expressing neurons.SIGNIFICANCE STATEMENT Parental care is critical for offspring survival. Compared with maternal care, however, the neurobiology of paternal care is less well understood. Here we show that the hormone prolactin, which is most well known for its female-specific role in lactation, has a role in the male brain to promote paternal behavior. In the absence of prolactin signaling specifically during interactions with pups, father mice fail to show normal retrieval behavior of pups. These data demonstrate that prolactin has a similar action in both males and females to promote parental care.

Project description:IntroductionIn most mammals, paternal care is not mandatory for raising offspring. In house mice, experience with pups governs the extent and quality of paternal care. First-time fathers undergo a dramatic transition from ignoring or killing pups to caring for pups. The behavioral shift occurs together with changes in brain estrogen signaling as indicated by changes in estrogen receptor presence and distribution in multiple areas regulating olfaction, emotion, and motivation.MethodsWe measured changes in the expression of aromatase, the enzyme converting testosterone into estrogen, as an indirect measure of estrogen synthesis, in various areas of the limbic system in mice with increasing paternal experience.ResultsThe amount of paternal experience (5 or 27 days) was associated with increased numbers of immunocytochemically-identified aromatase expressing cells in the medial and cortical amygdala, posterior piriform cortex, and ventromedial hypothalamus. Functionally, these changes can be related to the disappearance of aggression or neglect towards pups when first-time fathers or, even more, well-experienced fathers are handling their own pups. In the lateral septum, the anterior piriform cortex and to some extent in the medial preoptic area, parental experience increased the number of aromatase-positive cells only in fathers with 27 days of experience, and only in the right hemisphere. This represents a novel case of brain-functional lateralization triggered by experience. Nuclei/areas associated with maternal care (medial preoptic area, bed nucleus of stria terminalis, nucleus accumbens) exhibited a left-hemisphere advantage in aromatase expressing cells, both in pup-naïve and pup-experienced males. This newly found lateralization may contribute to the left-hemisphere dominant processing and perception of pup calls to release parental behavior.ConclusionIn general, the experience-dependent changes in aromatase expression we observed in most brain areas did not mirror the previously reported changes in estrogen receptors (ERα) when pup-naïve males became pup-caring fathers. Hence, paternal behavior may depend, in a brain area-specific way, on the differential action of estrogen through its receptors and/or direct local modulation of neural processing.

Dataset Information

Altered gut microbiome and autism like behavior are associated with parental high salt diet in male mice.

Publications

Altered gut microbiome and autism like behavior are associated with parental high salt diet in male mice.

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