AQP4, Astrogenesis, and Hydrocephalus: A New Neurological Perspective

Abstract

Aquaporin 4 (AQP4) is a cerebral glial marker that labels ependymal cells and astrocytes’ endfeet and is the main water channel responsible for the parenchymal fluid balance. However, in brain development, AQP4 is a marker of glial stem cells and plays a crucial role in the pathophysiology of pediatric hydrocephalus. Gliogenesis characterization has been hampered by a lack of biomarkers for precursor and intermediate stages and a deeper understanding of hydrocephalus etiology is needed. This manuscript is a focused review of the current research landscape on AQP4 as a possible biomarker for gliogenesis and its influence in pediatric hydrocephalus, emphasizing reactive astrogliosis. The goal is to understand brain development under hydrocephalic and normal physiologic conditions.

Calpeptin mitigates ventriculomegaly and microvascular impairment in a novel LPS- dependent mouse model of acquired hydrocephalus

“…The injections were performed in the right lateral ventricle following stereotactic coordinates (0.8 mm lateral, 1.7 mm anterior, and 1.5 mm deep from the posterior fontanelle) as previously described 21 . The solutions were administered over 30 seconds using a 25-microliter syringe (Hamilton, 80366) adapted to a UMP3 Ultra Micropump (World Precision Instruments) as previously reported 22,23 . The animals were anesthetized for hypothermia.…”

Effects of Aloe-Emodin on the Expression of Brain Aquaporins and Secretion of Neurotrophic Factors in a Rat Model of Post-Stroke Depression

“…It is involved in brain edema caused by ischemia and other injuries, as well as in reactive astrocyte migration and glial scarring that occur after traumatic brain injury. AQP1, 3, 4, 5, 8, and 9 have been reported to be expressed to some extent in the brain [ 22 , 23 ], but the functions of AQP3 and 5 remain unclear. The co-expression of aquaporins in astrocytes results in cell swelling and then activates the transient receptor potential vanillin 4 (TRPV4) channels with a quick response to increased cell volume.…”

Special Issue “Aquaporins in Brain Disease”

“…Castañeyra-Ruiz et al [ 7 ] revealed interesting data, proposing AQP4 as a possible biomarker for gliogenesis and ways in which alterations in AQP4 expression can be associated with pediatric hydrocephalus, with a specific emphasis on the repercussion of reactive astrogliosis in this pathological condition. According to Castañeira-Ruiz [ 7 ], unpolarized expression of AQP4 is found in proliferative cells with different morphologies in the human brain: in glial stem cells with long projections that are used for other cells to migrate and populate white matter tracks, and intermediate progenitor cells with an oval shape and lack of long projection. From these early stages of astrogenesis, AQP4 is expressed in polarized astrocyte endfeet, indicating the final stage of astrocyte maturation.…”

“…These findings allow the authors to suggest the possible role of AQP4 in the early cell differentiation process during the first days of life in the newborn animal, which may be important for myelinization. Furthermore, as indicated by Castañeira-Ruiz et al in their review [ 7 ], in different animal models that end up developing congenital or perinatal hydrocephalus, changes in AQP4 expression cause premature differentiation of glial stem cells (GSC) into reactive astrocytes, causing neurodevelopmental disorders. This occurs because GSCs lose their projections toward the white matter tracks and glioblasts then lose their migration guidance for the correct formation of white matter, a typical finding observed in pediatric hydrocephalus.…”

“…This occurs because GSCs lose their projections toward the white matter tracks and glioblasts then lose their migration guidance for the correct formation of white matter, a typical finding observed in pediatric hydrocephalus. Partial agenesis or hypoplasia of the corpus callosum is seen in patients with spina bifida, cases of obstructive hydrocephalus, and often in patients with a posthemorrhagic hydrocephalus [ 7 ]. Finally, in line with the relevant role of AQP4 in congenital hydrocephalus, the work of García-Bonilla et al [ 9 ] showed evidence that the injection of bone marrow-derived mesenchymal stem cells (BM-MSC) into the lateral ventricles of hydrocephalic mice (hyh) produced an astrocyte reaction that elicited an important overexpression of AQP4, together with induction of other neuronal process, and an overexpression of nerve growth factor (NGF) and vascular endothelia growth factor (VEGF), in addition to other factors that lead to recovery of the hydrocephalus condition.…”