title: Role of VEGF and VEGFR2 Receptor in Reversal of ALS-CSF Induced Degeneration of NSC-34 Motor Neuron Cell Line.
abstract: Vascular endothelial growth factor (VEGF), the well-known angiogenic factor is both neurotrophic and neuroprotective. Altered VEGF signalling is implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), a fatal degenerative disease of motor neurons. We have shown earlier that VEGF protects NSC-34 motor neuronal cell line, when exposed to cerebrospinal fluid (CSF) from sporadic ALS patients (ALS-CSF). Here, we have investigated the consequences of ALS-CSF and VEGF supplementation on the VEGFR2 receptor and endogenous VEGF expression. ALS-CSF caused significant down-regulation of VEGFR2 as well as the Calbindin-D28K levels, but not endogenous VEGF. Exogenous supplementation restored the depletion of VEGFR2 and Calbindin-D28K with a concomitant up-regulation of endogenous VEGF. The up-regulated caspase 3 in the ALS-CSF group was reinstated to basal levels along with a significant reduction in the number of TUNEL-positive cells. Electron photomicrographs of ALS-CSF-exposed cells divulged presence of cytoplasmic vacuoles alongside severe damage to organelles like mitochondria, endoplasmic reticulum, etc. Substantial recovery of most of the damaged organelles was noted in response to VEGF supplementation. While the enhancement in endogenous VEGF levels highlights the autocrine functions, the up-regulation of VEGFR2 receptor emphasizes the paracrine functions of VEGF in modulating its neuroprotective effect against ALS-CSF. The revival of cellular organellar structure, increased calbindin expression and enhanced survival in response to VEGF supplementation consolidates the opinion that VEGF indeed has a therapeutic potential in sporadic ALS.
authors.affiliation: Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Hosur Road, Bangalore, 560 029, India.
authors.forename: K
authors.initials: K
authors.lastname: Vijayalakshmi
authors.forename: Piyush
authors.initials: P
authors.lastname: Ostwal
authors.forename: R
authors.initials: R
authors.lastname: Sumitha
authors.forename: S
authors.initials: S
authors.lastname: Shruthi
authors.forename: Anu Mary
authors.initials: AM
authors.lastname: Varghese
authors.forename: Poojashree
authors.initials: P
authors.lastname: Mishra
authors.forename: S Gowri
authors.initials: SG
authors.lastname: Manohari
authors.forename: B C
authors.initials: BC
authors.lastname: Sagar
authors.forename: T N
authors.initials: TN
authors.lastname: Sathyaprabha
authors.forename: A
authors.initials: A
authors.lastname: Nalini
authors.forename: T R
authors.initials: TR
authors.lastname: Raju
authors.forename: Phalguni Anand
authors.initials: PA
authors.lastname: Alladi
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid* / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000134:cerebrospinal fluid / Q000378:metabolism; D002460:Cell Line; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000134:cerebrospinal fluid* / Q000494:pharmacology / Q000502:physiology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000502:physiology*
chemical_list: D015415:Biomarkers; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2