Elevated Levels of Neurotrophins in Human Biceps Brachii Tissue of Amyotrophic Lateral Sclerosis

• Published in: Experimental neurology Vol. 177; no. 2; pp. 419 - 427
• Main Authors: Küst, B.M., Copray, J.C.V.M., Brouwer, N., Troost, D., Boddeke, H.W.G.M.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01-10-2002; Elsevier
• Subjects: Adult; Aged; amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - metabolism; Amyotrophic Lateral Sclerosis - pathology; BDNF; Biological and medical sciences; Brain-Derived Neurotrophic Factor - genetics; Brain-Derived Neurotrophic Factor - metabolism; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Progression; ELISA; Enzyme-Linked Immunosorbent Assay; Female; Humans; In Situ Hybridization; Male; Medical sciences; Middle Aged; motoneuron; muscle; Muscle, Skeletal - chemistry; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Nerve Growth Factor - genetics; Nerve Growth Factor - metabolism; Nerve Growth Factors - genetics; Nerve Growth Factors - metabolism; Neurology; neurotrophin; Neurotrophin 3 - genetics; Neurotrophin 3 - metabolism; NGF; NT-3; NT-4/5; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; RNA, Messenger - metabolism; BDNF; muscle; NT-3; motoneuron; neurotrophin; NGF; amyotrophic lateral sclerosis; NT-4/5; ELISA; Human; Neurotrophin; Nervous system diseases; Nerve growth factor; Amyotrophic lateral sclerosis; Motor neuron; Biceps muscle; Pathology; Central nervous system disease; Degenerative disease; Degeneration; Brain derived neurotrophic factor; Spinal cord disease
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1006/exnr.2002.8011

Previous studies suggest that neurotrophins support regeneration and survival of injured motoneurons. Based on these findings, brain-derived neurotrophic factor (BDNF) has been clinically investigated for its therapeutic potential in amyotrophic lateral sclerosis (ALS), a rapidly progressing and fatal motoneuronal disease. We questioned whether imbalances of neurotrophic levels are indeed involved in the pathology of ALS. Therefore the expression of nerve growth factor (NGF), BDNF, neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5) was investigated in postmortem muscle tissue of the biceps from 15 patients with neuropathologically confirmed sporadic ALS and 15 age-matched controls. Using mRNA analysis techniques and quantitative protein measurements, we have demonstrated that both mRNA and protein levels of all four neurotrophins are increased in muscle tissue of ALS patients. The production levels displayed a disease duration dependency and different expression patterns emerged for the four neurotrophins. Whereas the early phase of the disease was characterized by a strong upregulation of BDNF, levels of NGF, NT-3, and NT-4/5 gradually increased in the course of the disorder, peaking at later stages. We conclude that decreased neurotrophic support from muscle tissue is most likely not the cause of motoneuron degeneration in ALS. On the contrary, our results suggest that degenerating motoneurons in ALS are exposed to elevated levels of muscle-derived neurotrophins.