Involvement of an Aberrant Vascular System in Neurodevelopmental, Neuropsychiatric, and Neuro-Degenerative Diseases

Abstract

The vascular system of the prenatal brain is crucial for the development of the central nervous system. Communication between vessels and neural cells is bidirectional, and dysfunctional communication can lead to neurodevelopmental diseases. In the present review, we introduce neurodevelopmental and neuropsychiatric diseases potentially caused by disturbances in the neurovascular system and discuss candidate genes responsible for neurovascular system impairments. In contrast to diseases that can manifest during the developing stage, we have also summarized the disturbances of the neurovascular system in neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. Furthermore, we discussed the role of abnormal vascularization and dysfunctional vessels in the development of neurovascular-related diseases.

Keywords: neurodegenerative disease; neurodevelopmental disease; neuropsychiatric disease; vascular system.

Figure 1

Tbx1 possibly relates to vascular abnormalities in 22qDS and DS. Triplication of Erg gene reduces prenatal cortical neurogenesis. ERG is dominantly expressed in endothelial cells and is suggested to play a role in angiogenesis. In DS, increased expression of certain gene(s) in Hsa21 decreases the expression of Tbx1. In 22qDS, a 3 Mb or a nested 1.5 Mb deletion of Hsa22q11.2 includes the TBX1 gene. TBX1 is suggested to play a role in cortical lamination and prenatal cortical neurogenesis. Thus, TBX1 may be involved in the molecular mechanism of common aspects in these syndromes, such as intellectual disability.

Figure 2

Neurovascular unit and cerebrovascular abnormality-related neurodegenerative pathways in AD pathophysiology. The relationship between vascular and brain component cells in the predicted AD pathology is depicted, including key neurodegenerative molecules. Aβ, amyloid-β; AD, Alzheimer’s disease; BBB, blood-brain barrier; IL, interleukin; MCP-1, monocyte chemoattractant protein-1; MMPs, matrix metalloproteinases; ROS, reactive oxygen species.