BDNF Serum Levels with Respect to Multidimensional Assessment in Amyotrophic Lateral Sclerosis

Tremolizzo, Lucio; Pellegrini, Andrea; Conti, Elisa; Arosio, A; Gerardi, Francesca; Lunetta, Christian; Magni, Paolo; Appollonio, Ildebrando; Ferrarese, Carlo

doi:10.1159/000441916

Cited by 22 publications

(13 citation statements)

References 51 publications

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“…However, in our study, the presumable BDNF mobilization was not reflected in its significant concentration increase in CSF. Interestingly, recent results by Tremolizzo et al point out an opposite correlation of serum BDNF with clinical outcome compared to our observation [55], though it is unclear whether the type of sample (plasma vs. serum) could play a role here. The varying levels of BDNF in circulation of patients with neurodegenerative diseases once again support the idea of intrathecal administration of cells secreting BDNF so that it can act in the site of the injury.…”

Section: Discussioncontrasting

confidence: 85%

Local and Systemic Humoral Response to Autologous Lineage-Negative Cells Intrathecal Administration in ALS Patients

Baumert

Sobuś

Gołąb-Janowska

et al. 2020

IJMS

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Amyotrophic lateral sclerosis (ALS) remains a fatal disease with limited therapeutic options. Signaling via neurotrophins (NTs), neuroinflammation, and certain micro-RNAs are believed to play essential role in ALS pathogenesis. Lineage-negative stem/progenitor cells (Lin−) were obtained from bone marrow of 18 ALS patients and administered intrathecally. Clinical assessment was performed using ALS Functional Rating Scale (FRSr) and Norris scale. Protein concentrations were measured in plasma and cerebrospinal fluid (CSF) by multiplex fluorescent bead-based immunoassay. Gene expression in nucleated blood cells was assessed using gene microarray technique. Finally, miRNA expression was analyzed using qPCR in CSF and plasma samples. We observed a significant decrease of C-reactive protein (CRP) concentration in plasma on the seventh day from the application of cells. Gene array results revealed decreased expression of gene sets responsible for neutrophil activation. Further analysis revealed moderate negative correlation between CRP level in CSF and clinical outcome. Brain-derived neurotrophic factor (BDNF) concentrations in both plasma and CSF significantly correlated with the favorable clinical outcome. On a micro-RNA level, we observed significant increase of miR-16-5p expression one week after transplantation in both body fluids and significant increase of miR-206 expression in plasma. Administration of Lin− cells may decrease inflammatory response and prevent neurodegeneration. However, these issues require further investigations.

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Section: Discussioncontrasting

confidence: 85%

Local and Systemic Humoral Response to Autologous Lineage-Negative Cells Intrathecal Administration in ALS Patients

Baumert

Sobuś

Gołąb-Janowska

et al. 2020

IJMS

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“…BDFN1 expression has been found alterated serum levels in subjects with different intensity of cognitive impairment and different neurodegenerative processes ( Angelucci et al, 2010 ; Siuda et al, 2017 ). Interestingly, in a cohort of serum samples from 45 ALS outpatients (16% bulbar onset), BDNF serum levels were significantly lower in ALS patients expressing lower ALSFRS-R scores ( r = 0.39, p < 0.01), which is a predictor for ALS-progression ( Tremolizzo et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Wide-Ranging Analysis of MicroRNA Profiles in Sporadic Amyotrophic Lateral Sclerosis Using Next-Generation Sequencing

et al. 2018

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MicroRNA (miRNA) has emerged as an important regulator of gene expression in neurodegenerative disease as amyotrophic lateral sclerosis (ALS). In the nervous system, dysregulation in miRNA-related pathways is subordinated to neuronal damage and cell death, which contributes to the expansion of neurodegenerative disorders, such as ALS. In the present research, we aimed to profile dysregulation of miRNAs in ALS blood and neuromuscular junction as well as healthy blood control by next-generation sequencing (NGS). The expression of three upregulated miRNAs, as miR-338-3p, miR-223-3p, and miR-326, in the ALS samples compared to healthy controls, has been validated by qRT-PCR in a cohort of 45 samples collected previously. Bioinformatics tools were used to perform ALS miRNAs target analysis and to predict novel miRNAs secondary structure. The analysis of the NGS data identified 696 and 49 novel miRNAs which were differentially expressed in ALS tissues. In particular, in neuromuscular junction the differential expression of miR-338-3p, which we previously found upregulated in different types of ASL tissues, miR-223-3p, and miR-326 was elevated compared to normal control. ALS miRNAs gene target were significantly involved in neuronal related pathway as BDFN1 and HIF-1genes. This study presents the direct experimental evidence that, overall, miR-338-3p is highly expressed in ALS tissues including neuromuscular junction characterizing ALS from normal tissues. Beside, our analysis identified, for the first time, novel miRNAs highly expressed in ALS tissues. In conclusion, the results indicate that miRNAs has an important role in the diagnosis and treatment of ALS.

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“…Defective BDNF expression and/or function is thought to be associated with depression, schizophrenia, Alzheimer's disease (AD), Parkinson's disease (PD), and ALS (Hyman et al, 1991; Phillips et al, 1991; Holsinger et al, 2000; Castrén et al, 2007; Favalli et al, 2012; Libman-Sokołowska et al, 2015). Alterations of neurotrophic availability have been proposed as a pathogenic mechanism underlying ALS neurodegeneration (Duberley et al, 1997; Kawamoto et al, 1998; Nishio et al, 1998; Tremolizzo et al, 2016). Although therapeutic trials of BDNF infusion have failed to show significant clinical benefit (1999; Ochs et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

The Analysis of Two BDNF Polymorphisms G196A/C270T in Chinese Sporadic Amyotrophic Lateral Sclerosis

Tian

et al. 2017

Front. Aging Neurosci.

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Amyotrophic lateral sclerosis (ALS) is an ethnically heterogeneous motor neuron disease that results from the selective death of motor neurons in the brain and spinal cord. Brain-derived neurotrophic factor (BDNF) is widely distributed across the central and peripheral nervous systems and plays neurotrophic and other physiological roles in various brain regions. Alterations of neurotrophin availability have been proposed as a pathogenic mechanism underlying ALS neurodegeneration. Several genetic studies have shown a significant association between schizophrenia, Alzheimer's disease, and Parkinson's disease and certain BDNF polymorphisms, specifically G196A (rs6265) and C270T (rs56164415). However, the relationship between the G196A and C270T polymorphisms and ALS has never been investigated. We hypothesized that sporadic ALS (sALS) and disease susceptibility could arise due to BDNF polymorphisms and investigated the relationship between ALS and the BDNF polymorphisms G196A and C270T in a large Chinese cohort. We demonstrate that the frequency of the CT genotype and of the C270T T allele was significantly higher in the ALS group than in controls, although G196A was not associated with sALS. These data provide the first demonstration that the BDNF C270T polymorphism may be a candidate susceptibility locus for sALS, at least in Han Chinese.

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BDNF Serum Levels with Respect to Multidimensional Assessment in Amyotrophic Lateral Sclerosis

Cited by 22 publications

References 51 publications

Local and Systemic Humoral Response to Autologous Lineage-Negative Cells Intrathecal Administration in ALS Patients

Local and Systemic Humoral Response to Autologous Lineage-Negative Cells Intrathecal Administration in ALS Patients

Wide-Ranging Analysis of MicroRNA Profiles in Sporadic Amyotrophic Lateral Sclerosis Using Next-Generation Sequencing

The Analysis of Two BDNF Polymorphisms G196A/C270T in Chinese Sporadic Amyotrophic Lateral Sclerosis

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