Brain-derived neurotrophic factor secreted by the cerebral endothelium: A new actor of brain function?

Abstract

Low cerebral levels of brain-derived neurotrophic factor (BDNF), which plays a critical role in many brain functions, have been implicated in neurodegenerative, neurological and psychiatric diseases. Thus, increasing BDNF levels in the brain is considered an attractive possibility for the prevention/treatment of various brain diseases. To date, BDNF-based therapies have largely focused on neurons. However, given the cross-talk between endothelial cells and neurons and recent evidence that BDNF expressed by the cerebral endothelium largely accounts for BDNF levels present in the brain, it is likely that BDNF-based therapies would be most effective if they also targeted the cerebral endothelium. In this review, we summarize the available knowledge about the biology and actions of BDNF derived from endothelial cells of the cerebral microvasculature and we emphasize the remaining gaps and shortcomings.

Dysfunction of Cerebrovascular Endothelial Cells: Prelude to Vascular Dementia

“…Since the normal BDNF expression is eNOS-dependent, BNDF function is also impaired when eNOS is dysfunctional. The decreased BDNF level leads to impaired angiogenesis, neuronal survival, as well as, synaptic plasticity, whereby cognitive impairment occurs ( Marie et al, 2018 ).…”

Engineering Brain-Specific Pericytes from Human Pluripotent Stem Cells

“…65 Cultured brain PCs were reported to secrete neurotrophic factors at the levels comparable to cultured astrocytes. 59,66 The PCconditioned media were found to increase the Akt phosphorylation simulated by insulin and insulin receptor b phosphorylation, suggesting that PCs can release soluble factors to increase the sensitivity of hypothalamic neurons to insulin. 11,67 These results indicate that PCs function as initial sensors of external insults and then relay the signals to the CNS.…”

Links Between Adiponectin and Dementia: From Risk Factors to Pathophysiology

“…Endothelial cells secrete a variety of vasodilators (e.g., NO, prostaglandins) and vasoconstrictors (e.g., endothelin ET, thromboxane A2), thereby regulating vasoconstriction and altering cerebral perfusion (Vanhoutte et al, 2017). Meanwhile, the endothelium is also essential to maintain the blood-brain barrier (BBB) for bidirectional molecular transmission between brain and other organs of the body (Sweeney et al, 2019) and exerts crucial trophic effects on brain cells (Marie et al, 2018). Previous studies demonstrated that hypertension causes severe damage to vascular endothelial cells, which in turn leads to BBB permeability changes, dysfunction of cerebral vascular and perivascular, and brain structural failure, including subclinical brain infarcts, white matter hyperintensities, and cerebral microbleeds (Iadecola and Gottesman, 2019).…”