MyD88 Deficiency, but Not Gut Microbiota Depletion, Is Sufficient to Modulate the Blood-Brain Barrier Function in the Mediobasal Hypothalamus.

ABSTRACT: Circumventricular organs (CVOs), including the mediobasal hypothalamus (MBH), have an incomplete blood-brain barrier (BBB). In this study, we determined if the BBB function in the MBH is modulated by the gut microbiota or by the Toll-like receptor (TLR) adapter proteins TRIF or MyD88 signaling. By injecting mice with Evans blue, a marker for BBB permeability, we show that germ-free (GF) and conventionally raised (CONV-R) mice did not differ in the number of Evans blue-positive cells in MBH. Acute modulation of the gut microbiota did not change the number of Evans blue-positive cells. In contrast, CONV-R Myd88^-/- and Trif^-/- mice had a reduced number of cells in direct contact to the circulation compared to wildtype (WT) mice. This was accompanied by increased tight junction proteins in the blood vessels in Myd88^-/- mice. To further characterize the BBB function, we injected WT and Myd88 ^-/- CONV-R mice as well as WT GF mice with monosodium glutamate (MSG), a neurotoxin that does not cross the BBB. While MSG caused vast cell death in the MBH in CONV-R and GF WT mice, Myd88 ^-/- mice were protected from such cell death suggesting that fewer cells are exposed to the neurotoxin in the Myd88 ^-/- mice. Taken together, our results suggest that MyD88 deficiency, but not gut microbiota depletion, is sufficient to modulate the BBB function in the MBH.

SUBMITTER: Heiss CN 

PROVIDER: S-EPMC9148286 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature