Protective effects of BDNF and NT-3 but not PDGF against hypoglycemic injury to cultured striatal neurons.
Brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and platelet-derived growth factor (PDGF) exert trophic effects on striatal neurons in vitro, which raises the possibility that these growth factors might also counteract neuronal death provoked by various insults. We have found that BDNF and NT-3, but neither PDGF-AA nor -BB, added 24 h before the insult ameliorated hypoglycemic neuronal damage induced by 15 or 24 h of glucose deprivation in rat striatal cell cultures. BDNF and NT-3 afforded neuronal protection even when administered 8 or 4 h, respectively, after the onset of hypoglycemia. In normoglycemic striatal cultures exposed to these neurotrophins for several days, there was a slight, nonsignificant increase of the number of surviving microtubule-associated protein-2-positive cells (20-30%) compared to untreated control cultures, but no change of glial cells. Exposure of the cultures to BDNF or NT-3 produced a significant increase in the number of neurons expressing detectable levels of the calcium-binding protein, calbindin, suggesting that a stabilization of calcium homeostasis might be implicated in the neuroprotection. Immunocytochemical analysis revealed that the majority (70-80%) of neurons in the striatal cultures expressed TrkB and TrkC, the functional receptors for BDNF and NT-3, respectively, implying that the effects of the neurotrophins are most likely direct. These data indicate that BDNF and NT-3 can protect striatal neurons against hypoglycemia in vitro and raise the possibility that these neurotrophins could counteract striatal neuronal death induced by hypoglycemic and ischemic insults in vivo.
Nakao
N
N
Department of Neurology, University Hospital, Lund, Sweden.
Kokaia
Z
Z
Odin
P
P
Lindvall
O
O
D000818:Animals; D001927:Brain Diseases / Q000209:etiology* / Q000517:prevention & control*; D019208:Brain-Derived Neurotrophic Factor; D064026:Calbindins; D003342:Corpus Striatum / Q000737:chemistry / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007003:Hypoglycemia / Q000150:complications*; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000032:analysis; D009414:Nerve Growth Factors / Q000627:therapeutic use*; D009419:Nerve Tissue Proteins / Q000627:therapeutic use*; D009474:Neurons / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020933:Neurotrophin 3; D010982:Platelet-Derived Growth Factor / Q000627:therapeutic use*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D020801:Receptor, Ciliary Neurotrophic Factor; D020812:Receptor, trkC; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D064026:Calbindins; D005904:Glial Fibrillary Acidic Protein; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D020933:Neurotrophin 3; D010982:Platelet-Derived Growth Factor; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D064030:S100 Calcium Binding Protein G; D020794:Receptor Protein-Tyrosine Kinases; D020812:Receptor, trkC