Structural and Functional Features of Developing Brain Capillaries, and Their Alteration in Schizophrenia

Abstract

Schizophrenia affects more than 1% of the world’s population and shows very high heterogeneity in the positive, negative, and cognitive symptoms experienced by patients. The pathogenic mechanisms underlying this neurodevelopmental disorder are largely unknown, although it is proposed to emerge from multiple genetic and environmental risk factors. In this work, we explore the potential alterations in the developing blood vessel network which could contribute to the development of schizophrenia. Specifically, we discuss how the vascular network evolves during early postnatal life and how genetic and environmental risk factors can lead to detrimental changes. Blood vessels, capillaries in particular, constitute a dynamic and complex infrastructure distributing oxygen and nutrients to the brain. During postnatal development, capillaries undergo many structural and anatomical changes in order to form a fully functional, mature vascular network. Advanced technologies like magnetic resonance imaging and near infrared spectroscopy are now enabling to study how the brain vasculature and its supporting features are established in humans from birth until adulthood. Furthermore, the contribution of the different neurovascular unit elements, including pericytes, endothelial cells, astrocytes and microglia, to proper brain function and behavior, can be dissected. This investigation conducted among different brain regions altered in schizophrenia, such as the prefrontal cortex, may provide further evidence that schizophrenia can be considered a neurovascular disorder.

Compositional Features and Nutritional Value of Pig Brain: Potential and Challenges as a Sustainable Source of Nutrients

“…This was attributed to the presence of a blood vessel in the brain, which is evident in Table 1 . Blood vessels, particularly capillaries, form a dynamic and intricate architecture that transports oxygen and nutrients to the brain [ 38 ]. As food, the presence of heme protein in form of blood may influence the storage stability, specifically, discoloration, rancidity development, and microbial growth [ 13 , 39 , 40 ].…”

From Neurodevelopmental to Neurodegenerative Disorders: The Vascular Continuum

“…A dysfunctional BBB has been reported in schizophrenia, with increased permeability to damaging proteins (Müller and Ackenheil, 1995;Shcherbakova et al, 1999;Crockett et al, 2021). Studies are starting to decipher changes in cells associated with the BBB (for a detailed review, see Carrier et al, 2020). Briefly, evidence of schizophrenia-associated microvascular abnormalities in the neocortex include thickening and deformation of basal lamina, vacuolation of cytoplasm in ECs, basal lamina and astrocytic end-feet, swelling of astrocyte end-feet, activation of microglial cells in the prefrontal and visual cortex, as well as atypical vascular arborization (Uranova et al, 2010;Carrier et al, 2020).…”

“…Moreover, specific mutations are associated with schizophrenia, including alterations in the 22q11.2 deletion syndrome (22qDS) -strongest monogenic risk allele for this disorder, and polymorphisms in claudin-5, a densely expressed tight junction molecule (Gur et al, 2017;Greene et al, 2018;Carrier et al, 2020) altogether revealing barrier dysfunction in schizophrenia patients (Greene et al, 2018;Crockett et al, 2021). Post-mortem brain sections from 22qDS patients and animal models of 22qDS both demonstrate reduced claudin-5 expression in the BBB, which in turn compromised BBB function (Nishiura et al, 2017;Guo et al, 2020;Crockett et al, 2021;Usta et al, 2021).…”

“…-Impaired angiogenesis and VEGF upregulation in the prefrontal cortex linked to vascular hyperpermeability. Grove et al, 2015;Hino et al, 2016;Casas et al, 2018;Carrier et al, 2020;Cai et al, 2020;Guo et al, 2020;Crockett et al, Ge et al, 2005;Varga et al, 2009;D'Haeseleer et al, 2011;Ota et al, 2013;Marshall et al, 2014;Bester et al, 2015;Monti et al, 2018;Hostenbach et al, 2019 Altered BBB and angiogenesis -BBB hyperpermeability.…”

Translational control in neurovascular brain development

“…There are a substantial number of human and experimental studies identifying possible mechanisms that induce increased oxidative stress and neuroinflammation, such as the increased VEGF activity [165,166] and microglial activation [168][169]. These mechanisms (extensively reviewed in [170]) strongly suggest NVU dysfunction and BBB hyperpermeability in SZ brain, providing a link between the vascular and the nervous system in the disease; however, whether the vasculature deficits are a cause or a consequence of the deficient brain development still remains unclear [171]. Recent studies in ASD patients revealed alterations in angiogenesis in post-mortem brain, shown by aberrant staining of pericytes [172] and changes in cerebral blood flow [173].…”