Bi-directionally protective communication between neurons and astrocytes under ischemia

Abstract

The extensive existing knowledge on bi-directional communication between astrocytes and neurons led us to hypothesize that not only ischemia-preconditioned (IP) astrocytes can protect neurons but also IP neurons protect astrocytes from lethal ischemic injury. Here, we demonstrated for the first time that neurons have a significant role in protecting astrocytes from ischemic injury. The cultured medium from IP neurons (IPcNCM) induced a remarkable reduction in LDH and an increase in cell viability in ischemic astrocytes in vitro. Selective neuronal loss by kainic acid injection induced a significant increase in apoptotic astrocyte numbers in the brain of ischemic rats in vivo. Furthermore, TUNEL analysis, DNA ladder assay, and the measurements of ROS, GSH, pro- and anti-apoptotic factors, anti-oxidant enzymes and signal molecules in vitro and/or in vivo demonstrated that IP neurons protect astrocytes by an EPO-mediated inhibition of pro-apoptotic signals, activation of anti-apoptotic proteins via the P13K/ERK/STAT5 pathways and activation of anti-oxidant proteins via up-regulation of anti-oxidant enzymes. We demonstrated the existence of astro-protection by IP neurons under ischemia and proposed that the bi-directionally protective communications between cells might be a common activity in the brain or peripheral organs under most if not all pathological conditions.

Copper signalling: causes and consequences

“…Several lines of evidence demonstrate memory deficits concurrent with copper deposition in the choroid plexus, astrocyte swelling (Alzheimer type II cells), astrogliosis and neuronal degeneration in the cerebral cortex, and augmented levels of copper and zinc in the hippocampus of chronically copper-intoxicated rats [ 337 ]. Furthermore, these and the other findings concerning the role for astrocytes in brain activity, dis-homeostasis and asscociated diseases [ 110 , 338 – 341 ] and brain copper and pA homeostasis in particular [ 179 , 180 , 342 , 343 ] may provide support for new astrocyte-centric directions for therapeutic intervention. It can also be depicted by the “gliocentric” alternative of the “neurocentric” STP workflow suggested by Chang [ 336 ] possibly associated with major astroglial processes and players of Glu and ammonia homeostasis underlying excitation-inhibition balance in brain [ 110 ].…”

“…4 Copper signaling via neuro-glia coupling. Astroglia, a previously neglected cell type of the brain [ 340 ], operate a variety of copper-dependent metabolic functions [ 6 , 80 , 240 , 341 , 342 ]. For this reason, in addition to synaptic and extrasynaptic copper signalling by way of excitatory/inhibitory receptors and ionic channels [ 22 , 234 , 235 , 237 – 244 , 246 , 255 , 336 , 345 – 355 ], we place copper-dependent production of pAs in astrocytes [ 338 ] and correlated gap-junction modulation in the centre of this option.…”

A Framework for Identifying Genotypic Information from Clinical Records: Exploiting Integrated Ontology Structures to Transfer Annotations between ICD Codes and Gene Ontologies

“…Although the generated networks are from independent annotation datasets, interestingly, there is a notable overlap between the associations of the two networks (i.e 9 associations) which indicates that our ontology integration method is one of the promising efforts in merging the annotations from various ontologies. Moreover, the associations also suggest the potential genomic linkages uncovered from our integration between diseases, like hodgkin's sarcoma and malignant neoplasm of colon [30] , malignant neoplasm of larynx and hemangioma of unspecified site [31], [32] as well as liver necrosis and obstruction of bile duct [33], [34], [35]. These results suggest that our integrated ontology framework can be used to not only transfer annotations from one level to the other but can also facilitate comparison and understanding of relationships between the annotated groups at higher levels.…”

Glial function (and dysfunction) in the normal & ischemic brain

“…Astrocytic dysfunction in an ischemic lesion may result from abnormalities in ion buffering, uptake and synthesis of neurotransmitters, water transport, influences on cerebral blood flow, release of antioxidants, and even immunomodulation (Becerra-Calixto and Cardona-Gomez, 2017). Astrocytes are considered as supporting the energy needs of neurons, and there is evidence of ‘bi-directional’ communication between neurons and astrocytes under some ischemic conditions (Wu et al, 2017). Astrocytes show a high glycolytic rate and show high expression of relevant enzymes (e.g.…”