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

Autor: Christina N. Heiss, Ellinor Gravert, Matilda Hultén, Louise E. Olofsson
Rok vydání: 2022
Předmět:
Zdroj: Molecular Neurobiology. 59:3755-3766
ISSN: 1559-1182
0893-7648
DOI: 10.1007/s12035-022-02802-w
Popis: 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.
Databáze: OpenAIRE
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