Mouse galectin‐1 inhibits the toxicity of glutamate by modifying NR1 NMDA receptor expression

Abstract

One of the major causes of neuronal death in neurodegenerative disease is excitotoxicity from the neurotransmitter glutamate. This form of cell death could arise from either excess levels of glutamate due to decreased astrocyte clearance or due to increased susceptibility. We have identified galectin-1, a galactose-binding lectin, as a potential neuroprotective factor secreted by astrocytes. Our results show that both native and recombinant galectin-1 protects mouse and rat cerebellar neurons from the toxic effects of glutamate. Galectin-1 applied to neurons increased their expression of the NMDA receptor NR1 and increased the proportion of the NR1a subunit subtype while antisense knockdown of the NR1a receptor blocked the neuroprotective effect of galectin-1. This effect of the protein was dependent upon it carbohydrate recognition domain, suggesting that the protein acts in a reduced dimerized form. In addition, galectin-1 caused a decreased expression of PKC associated with increased resistance to glutamate toxicity. These results suggest that the astrocytic lectin galectin-1 could protect neurons against the effects of excitotoxicity as seen in stroke and ischemic injury.

Galectin-1 Enhances Astrocytic BDNF Production and Improves Functional Outcome in Rats Following Ischemia

“…Studies have showed that secreted endogenous Gal-1 can act on the relevant receptors and induce downstream effects [8]. We here showed that endogenous Gal-1 can be induced by anoxia, and exogenous Gal-1 contributed to the astrocytic BDNF production.…”

“…We would like to elucidate that recovery of ischemic rats might come from multiple effects of several pathways because Gal-1 takes a general role in CNS [8,10,38]. Although dependable data about the dose of astrocytic BDNF valuable for neuroprotection has not been identified, the increased production of astrocytic BDNF may partly mediate this neuroprotective effect at least.…”

“…In CNS, previous findings show that it is widely expressed in both neurons and glia [12,13] and has general effects after injuries. It has been reported to be involved in neurite outgrowth and synaptic connectivity of peripheral nerve, resistance to glutamate toxicity and cellular adaptation to redox status after stroke, proliferation of neural stem cells and cerebellar astrocytes, as well as production of inflammatory and neurotrophic factors after injuries [8,11,12,14,15]. Those studies suggest that Gal-1 may have therapeutic potential to prevent neuronal damage after stroke.…”

“…Galectin-1 (Gal-1) is a soluble carbohydrate-binding protein that has been implicated in a variety of biological events [8][9][10][11]. In CNS, previous findings show that it is widely expressed in both neurons and glia [12,13] and has general effects after injuries.…”

Galectin-1 as a Multifunctional Molecule in the Peripheral Nervous System After Injury

“…Enzymatic and mechanical treatments for the dissociation of DRG cells, together with disruption of interactions between neurons and non-neuronal cells are detrimental to neurons. Therefore, GAL-1 expressed in cultured neurons may function as a stress marker protein (Iwamoto et al, 2010) and/or a cytoprotective molecule (Lekishvili et al, 2006) during in vivo-in vitro replacement. Western blot analysis.…”