Brain-Derived Neurotrophic Factor Facilitates Functional Recovery from ALS-Cerebral Spinal Fluid-Induced Neurodegenerative Changes in the NSC-34 Motor Neuron Cell Line

• Published in: Neuro-degenerative diseases Vol. 17; no. 1; p. 44
• Main Authors: Shruthi, Shanmukha, Sumitha, R, Varghese, Anu Mary, Ashok, S, Chandrasekhar Sagar, B K, Sathyaprabha, T N, Nalini, A, Kramer, Boris W, Raju, Trichur R, Vijayalakshmi, K, Alladi, Phalguni Anand
• Format: Journal Article
• Language: English
• Published: Switzerland 01.11.2016
• Subjects: Amyotrophic Lateral Sclerosis - cerebrospinal fluid; Animals; Apoptosis - drug effects; Apoptosis - physiology; Brain-Derived Neurotrophic Factor - metabolism; Brain-Derived Neurotrophic Factor - pharmacology; Calcium - metabolism; Cell Line; Cell Survival - drug effects; Disease Models, Animal; Humans; Intermediate Filaments - drug effects; Intermediate Filaments - metabolism; Intermediate Filaments - pathology; Mice; Motor Neurons - drug effects; Motor Neurons - physiology; Motor Neurons - ultrastructure; Nerve Degeneration - drug therapy; Nerve Degeneration - pathology; Nerve Degeneration - physiopathology; Neuroprotective Agents - pharmacology; Rats, Wistar; Receptor, trkB - metabolism; Recovery of Function - drug effects; Recovery of Function - physiology; Spinal Cord - drug effects; Spinal Cord - pathology; Spinal Cord - physiopathology
• ISSN: 1660-2862
• DOI: 10.1159/000447559

The survival of motor neurons is dependent upon neurotrophic factors both during childhood and adolescence and during adult life. In disease conditions, such as in patients with amyotrophic lateral sclerosis (ALS), the mRNA levels of trophic factors like brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), fibroblast growth factor-2 (FGF-2), and vascular endothelial growth factor are downregulated. This was replicated in our in vivo experimental system following the injection of cerebral spinal fluid (CSF) of sporadic ALS (ALS-CSF) patients. To evaluate the protective role of BDNF in a model of sporadic ALS patients. The expressions of endogenous BDNF, its receptor TrkB, the enzyme choline acetyl transferase (ChAT), and phosphorylated neurofilaments were studied in NSC-34 cells. The calcium-buffering and proapoptotic effects were assessed by calbindin-D28K and caspase-3 expression, respectively. ALS-CSF considerably depleted the endogenous BDNF protein, while its effect on IGF-1 and FGF-2 was inconsequential; this indirectly indicates a key role for BDNF in supporting motor neuronal survival. The exogenous supplementation of BDNF reversed autocrine expression; however, it may not be completely receptor mediated, as the TrkB levels were not restored. BDNF completely revived ChAT expression. It may inhibit apoptosis by restoring Ca2+ homeostasis, since caspase-3 and calbindin-D28K expression was back to normal. The organellar ultrastructural changes were only partially reversed. Our study provides evidence that BDNF supplementation ameliorates most but not all degenerative changes. The incomplete revival at the ultrastructural level signifies the requirement of factors other than BDNF for near-total protection of motor neurons, and, to an extent, it explains why only a partial success is achieved in clinical trials with BDNF in ALS patients.