Angiogenin in the Neurogenic Subventricular Zone After Stroke

Abstract

Ischemic stroke is a leading cause of death and disability worldwide with effective acute thrombolytic treatments. However, brain repair mechanisms related to spontaneous or rehabilitation-induced recovery are still under investigation, and little is known about the molecules involved. The present study examines the potential role of angiogenin (ANG), a known regulator of cell function and metabolism linked to neurological disorders, focusing in the neurogenic subventricular zone (SVZ). Angiogenin expression was examined in the mouse SVZ and in SVZ-derived neural stem cells (NSCs), which were exposed to exogenous ANG treatment during neurosphere formation as well as in other neuron-like cells (SH-SY5Y). Additionally, male C57Bl/6 mice underwent a distal permanent occlusion of the middle cerebral artery to study endogenous and exercise-induced expression of SVZ-ANG and neuroblast migration. Our results show that SVZ areas are rich in ANG, primarily expressed in DCX+ neuroblasts but not in nestin+NSCs. In vitro, treatment with ANG increased the number of SVZ-derived NSCs forming neurospheres but could not modify SH-SY5Y neurite differentiation. Finally, physical exercise rapidly increased the amount of endogenous ANG in the ipsilateral SVZ niche after ischemia, where DCX-migrating cells increased as part of the post-stroke neurogenesis process. Our findings position for the first time ANG in the SVZ during post-stroke recovery, which could be linked to neurogenesis.

Neural stem cell homeostasis is affected in cortical organoids carrying a mutation in Angiogenin

“…It has been suggested that adult neurogenesis is altered in ALS-FTD [60]. ANG is also upregulated during adult neurogenesis in mice [61] and is expressed in the mouse subventricular zone after ischaemic stroke in the neuroblasts [34].…”

“…ANG is expressed in the developing mouse nervous system and has been shown to play a role in neuronal differentiation of mouse pluripotent cells, as well as in the developing zebrafish nervous system [1,2,30]. It is also expressed in the adult mouse subventricular zone and is implicated in neurogenesis during recovery from stroke [33,34]. Here we asked if ANG played a similar a role during neurogenesis using a human induced pluripotent stem cell (iPSC)‐derived model.…”

Endogenous Neural Stem Cell Activation after Low-Intensity Focused Ultrasound-Induced Blood–Brain Barrier Modulation

“…In the brain, new neurons are produced in the SVZ around the ventricle and the SGZ in the hippocampus, where neurogenesis occurs most actively and continuously [ 25 , 26 ]. Many studies have shown that when the brain is abnormal, the dividing neuroblasts move to the lesion location, and the migrated cells surround the lesion and slow its progression [ 27 , 28 , 29 ].…”

Functional Recovery and Serum Angiogenin Changes According to Intensity of Rehabilitation Therapy After Stroke

“…Additionally, in this previous study, experiments in pre-clinical stroke models also described an ANG increase in the ischemic site when performing task-specific exercise, suggesting an association between rehabilitation and molecular changes in the brain. Moreover, another pre-clinical study from our group has recently described that physical exercise rapidly increased the amount of endogenous ANG in the ipsilateral neurogenic subventricular zone after cerebral ischemia ( 40 ). All this evidence points to potential connections between ANG, stroke disease, and rehabilitation, although confirmatory investigations are needed.…”