PMID- 27617773
OWN - NLM
STAT- MEDLINE
DCOM- 20170726
LR  - 20171205
IS  - 1660-2862 (Electronic)
IS  - 1660-2854 (Linking)
VI  - 17
IP  - 1
DP  - 2017
TI  - Brain-Derived Neurotrophic Factor Facilitates Functional Recovery from 
      ALS-Cerebral Spinal Fluid-Induced Neurodegenerative Changes in the NSC-34 Motor 
      Neuron Cell Line.
PG  - 44-58
AB  - BACKGROUND: 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. OBJECTIVE: To evaluate the protective 
      role of BDNF in a model of sporadic ALS patients. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
CI  - (c) 2016 S. Karger AG, Basel.
FAU - Shruthi, Shanmukha
AU  - Shruthi S
AD  - Department of Neurophysiology, National Institute of Mental Health and 
      Neurosciences, Bangalore, India.
FAU - Sumitha, R
AU  - Sumitha R
FAU - Varghese, Anu Mary
AU  - Varghese AM
FAU - Ashok, S
AU  - Ashok S
FAU - Chandrasekhar Sagar, B K
AU  - Chandrasekhar Sagar BK
FAU - Sathyaprabha, T N
AU  - Sathyaprabha TN
FAU - Nalini, A
AU  - Nalini A
FAU - Kramer, Boris W
AU  - Kramer BW
FAU - Raju, Trichur R
AU  - Raju TR
FAU - Vijayalakshmi, K
AU  - Vijayalakshmi K
FAU - Alladi, Phalguni Anand
AU  - Alladi PA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160913
PL  - Switzerland
TA  - Neurodegener Dis
JT  - Neuro-degenerative diseases
JID - 101189034
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neuroprotective Agents)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - SY7Q814VUP (Calcium)
RN  - Amyotrophic lateral sclerosis 1
SB  - IM
MH  - Amyotrophic Lateral Sclerosis/*cerebrospinal fluid
MH  - Animals
MH  - Apoptosis/drug effects/physiology
MH  - Brain-Derived Neurotrophic Factor/metabolism/*pharmacology
MH  - Calcium/metabolism
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Disease Models, Animal
MH  - Humans
MH  - Intermediate Filaments/drug effects/metabolism/pathology
MH  - Mice
MH  - Motor Neurons/*drug effects/physiology/ultrastructure
MH  - Nerve Degeneration/*drug therapy/pathology/physiopathology
MH  - Neuroprotective Agents/*pharmacology
MH  - Rats, Wistar
MH  - Receptor, trkB/metabolism
MH  - Recovery of Function/*drug effects/physiology
MH  - Spinal Cord/drug effects/pathology/physiopathology
EDAT- 2016/11/02 06:00
MHDA- 2017/07/27 06:00
CRDT- 2016/09/13 06:00
PHST- 2015/10/30 00:00 [received]
PHST- 2016/06/07 00:00 [accepted]
PHST- 2016/11/02 06:00 [pubmed]
PHST- 2017/07/27 06:00 [medline]
PHST- 2016/09/13 06:00 [entrez]
AID - 000447559 [pii]
AID - 10.1159/000447559 [doi]
PST - ppublish
SO  - Neurodegener Dis. 2017;17(1):44-58. doi: 10.1159/000447559. Epub 2016 Sep 13.