Effects of the microbiota on vasopressin neurons in the hypothalamic paraventricular nucleus of newborn mice
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Cornell, Abby
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Ragan, Christina
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Abstract
At birth, the mammalian newborn is massively colonized by microbes. We previously reported that the microbiota influences brain development. Specifically, we found that when compared to their conventionally colonized (CC) counterparts, sterile newborn mice (“germ-free” or GF) show higher cell death in the paraventricular nucleus of the hypothalamus (PVN), a key region for the body’s stress response and brain-immune interactions. This effect was associated with lower cell counts in the PVN, suggesting that the microbiota shapes brain structure. Here, we investigated the cell phenotypes that are altered by the absence of a microbiota. We focused on vasopressin (VP) neurons given that they participate in functions known to be altered in GF adult mice (e.g., stress response). To test whether any effects on VP neurons are influenced by microbial colonization at birth or programmed prenatally via the maternal microbiota, we used a cross-fostering approach. Specifically, we cross-fostered GF pups to CC dams (GF→CC) immediately after birth and compared them to control groups that were cross-fostered within microbial status (CC→CC and GF→GF). Pup brains were collected 3 days after birth and processed for immunohistochemical detection of VP neurons. We found that the microbiota did not influence overall VP-immunopositive neuron number in the PVN. However, the microbiota did influence the number of VP-immunopositive neurons in the rostral PVN but in an unexpected way: GF→GF pups had more VP neurons than CC→CC pups. This result suggests that the microbiota has cell phenotype-dependent effects within the PVN. Interestingly, the effect on the GF PVN was normalized by microbial postnatal exposure at birth, as GF→CC pups were no different from CC→CC pups, and different from the GF→GF group. A similar effect was found for VP soma size, but this did not reach statistical significance. Our results suggest that the arrival of the microbiota at birth has phenotype-specific cellular influences in the PVN.
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