Agrin Involvement in Synaptogenesis Induced by Exercise in a Rat Model of Experimental Stroke

Abstract

Background Agrin is a proteoglycan that aggregates nicotinic acetylcholine receptors (AChRs) on neuromuscular junctions and takes part in synaptogenesis in the development of the central nervous system. However, its effects on neural repair and synaptogenesis after stroke are still unclear. Objective This study aimed to investigate the effects of agrin on neural repair and synaptogenesis after stroke and the effects of exercise on this process in vivo and in vitro. Methods Exercise with gradually increased intensity was initiated at 1 day after middle cerebral artery occlusion (MCAO) for a maximum of 14 days. Neurological deficit scores and foot fault tests were used to assess the behavioral recovery. Western blotting, immunofluorescence, and electron microscopic images were used to detect the expression of agrin, synaptogenesis-related proteins, and synaptic density in vivo. In vitro, the ischemic neuron model was established via oxygen-glucose deprivation (OGD). The lentivirus overexpressed agrin and CREB inhibitor were used to investigate the mechanism by which agrin promoted synaptogenesis. Results Exercise promoted behavioral recovery and this beneficial role was linked to the upregulated expression of agrin and increased synaptic density. Overexpressed agrin promoted synaptogenesis in OGD neuron, CREB inhibitor downregulated the expression of agrin and hampered synaptogenesis in cultured neurons. Conclusions These results indicated that exercise poststroke improved the recovery of behavioral function after stroke. Synaptogenesis was an important and beneficial factor, and agrin played a critical role in this process and could be a potential therapeutic target for the treatment of stroke and other nervous system diseases.

Prediction of Sarcopenia Using Multiple Biomarkers of Neuromuscular Junction Degeneration in Chronic Obstructive Pulmonary Disease

“…Agrin plays an active role in re-innervation by promoting the recycling of AChRs at the motor endplate. As a consequence, exercise is associated with an upregulation of agrin at the NMJs [ 29 ]. Conversely, overexpression of neurotrypsin results in cleavage of agrin and reduced muscle strength and mass [ 30 ].…”

The Role of Astrocytes in the Neurorepair Process

“…They demonstrated that deficits in TSP-1/2 lead to difficulty in recovery after cerebral ischemia mainly due to the role of these proteins on the formation of synapses and in axonal appearance. In addition, they also confirm that TSPs are partially secreted by astrocytes after the stroke, which was evidenced by the co-localization of TSP-1 and TSP-2 with S100 and GFAP, respectively (Liauw et al, 2008;Zhang et al, 2020).…”

“…The poststroke exercise improved the recovery of behavioral function and agrin played a critical role in the synaptogenesis process. Due to that, Agrin can be considered a potential therapeutic target for the treatment of stroke and other diseases of the nervous system ( Zhang et al, 2020 ).…”

Into the Tissues: Extracellular Matrix and Its Artificial Substitutes: Cell Signalling Mechanisms

“…Such properties provide tissues with resistance to deformation by high physical forces, as exemplified by aggrecan, the most important cartilage proteoglycan [ 79 , 86 , 95 , 96 ]. The proteoglycan family also includes compounds, such as syndecans (trans-membrane receptors; they bind numerous ligands present in the ECM, mediate signal transduction, cell adhesion, migration et al) [ 97 , 98 ], serglycin (the only known intracellular proteoglycan; found in leukocyte granules, regulates granulopoiesis) [ 99 , 100 , 101 ], perlecan and agrin (characteristic of the basement membrane, regulators of many cellular processes; agrin is involved in the formation of neuromuscular synapses) [ 102 , 103 , 104 , 105 , 106 , 107 ] and fibromodulin (involved in the collagen fibrillogenesis) [ 108 , 109 ].…”