Muscle-conditioned media and cAMP promote survival and neurite outgrowth of adult spinal cord motor neurons

G, José V Montoya; Sutachán, Jhon-Jairo; Chan, Wai Si; Sideris, Alexandra; Blanck, Thomas J. J.; Recio-Pinto, Esperanza

doi:10.1016/j.expneurol.2009.09.003

Cited by 22 publications

(19 citation statements)

References 77 publications

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“…S7). MAP2 is a neuronal marker, and Islet-1 is a motor neuron-specific marker (30). Separate cell collections in wells derived from the same individual differentiation event were left unirradiated or were exposed to 25 J of UV-C and immunostained for FUS and either active RNA Pol II or γH2AX.…”

Section: Depletion Of Fus and Tdp43 Leads To Excessive Transcription mentioning

confidence: 99%

Two familial ALS proteins function in prevention/repair of transcription-associated DNA damage

Hill

Mordes

Cameron

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

107

119

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Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron dysfunction disease that leads to paralysis and death. There is currently no established molecular pathogenesis pathway. Multiple proteins involved in RNA processing are linked to ALS, including FUS and TDP43, and we propose a disease mechanism in which loss of function of at least one of these proteins leads to an accumulation of transcription-associated DNA damage contributing to motor neuron cell death and progressive neurological symptoms. In support of this hypothesis, we find that FUS or TDP43 depletion leads to increased sensitivity to a transcription-arresting agent due to increased DNA damage. Thus, these proteins normally contribute to the prevention or repair of transcription-associated DNA damage. In addition, both FUS and TDP43 colocalize with active RNA polymerase II at sites of DNA damage along with the DNA damage repair protein, BRCA1, and FUS and TDP43 participate in the prevention or repair of R loopassociated DNA damage, a manifestation of aberrant transcription and/or RNA processing. Gaining a better understanding of the role(s) that FUS and TDP43 play in transcription-associated DNA damage could shed light on the mechanisms underlying ALS pathogenesis.A myotrophic lateral sclerosis (ALS) is a disease of both upper and lower motor neuron dysfunction that leads to progressive paralysis and eventually death due to respiratory failure. No single model of ALS disease pathogenesis has been revealed; however, multiple disease-associated genes are known (1). The variation in function of these genes suggests that there may be multiple ALS molecular subtypes. That said, the familial ALS gene product list is also enriched in protein groups with related functions.Mutations in multiple RNA processing genes, including FUS (FUS RNA-binding protein), TDP43 (TAR DNA-binding protein), SETX (senataxin), TAF15 (TATA box-binding protein-associated factor 15), EWSR1 (EWS RNA-binding protein 1), HNRNPA1 (heterogeneous nuclear ribonucleoprotein A1), and HNRNPA2B1 (heterogeneous nuclear ribonucleoprotein A2/B1), among others, give rise to familial ALS (fALS) (1). FUS and TDP43 are currently the best studied, given that mutations in these genes lead to classic histologic findings in ALS neural tissue and that similar histologic findings can be found in neural tissue of sporadic ALS cases (2). At autopsy, cytoplasmic TDP43 inclusions are found in ALS motor neurons from patients with (i) TDP43 mutations and (ii) sporadic ALS (i.e., patients with no FUS, TDP43, or other known pathogenic mutation) (2). They are also present in neurons in various parts of the brains of patients with either sporadic or familial versions of the ALS-related disorder, fronto-temporal lobar dementia (FTLD) (2). At autopsy, FUS inclusions were detected in the cytoplasm of motor neurons of FUS mutation-bearing fALS patients and in the cytoplasm of neurons in various regions of the brain in some FTLD patients (2).FUS and TDP43 exhibit a wide range of functions, most of which involv...

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Section: Depletion Of Fus and Tdp43 Leads To Excessive Transcription mentioning

confidence: 99%

Two familial ALS proteins function in prevention/repair of transcription-associated DNA damage

Hill

Mordes

Cameron

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

107

119

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“…Immunocytochemistry can be performed using several motor neuron cell markers ( 26 ) at different time points. Electrically functional SCMNs can be found after 1 week of culture ( 26 ) and can be measured at different time points thereafter.…”

Section: Feeding Of Motor Neuron Culturesmentioning

confidence: 99%

“…The adult SCMNs obtained using this protocol (Fig. 3 ) express proteins and transcription factors selective to SCMNs such as the non-phosphorylated neurofi lament H, the transcription factors HB9 and Islet-1, and the enzyme choline acetyltransferase responsible for synthesis of the neurotransmitter acetylcholine ( 26 ) . These SCMNs also express the major synaptic protein synaptophysin (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…4 ) (data not published) that has been involved in regulating activity-dependent synapse formation ( 30 ) . Cultured SCMNs are also electrically active: They express outward K + currents as early as 1 h after plating, and, fast and slow inward currents become detectable after 1 week in culture ( 26 ) . Action potentials can also be evoked ( 26 ) .…”

Section: Introductionmentioning

confidence: 99%

“…Cultured SCMNs are also electrically active: They express outward K + currents as early as 1 h after plating, and, fast and slow inward currents become detectable after 1 week in culture ( 26 ) . Action potentials can also be evoked ( 26 ) . Calcium transients have been detected after 1 week of culture (Fig.…”

Section: Introductionmentioning

confidence: 99%

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Preparation of Adult Spinal Cord Motor Neuron Cultures Under Serum-Free Conditions

Montoya-Gacharna

Sutachán

Chan

et al. 2012

Neurotrophic Factors

Self Cite

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Spinal cord motor neuron cultures are an important tool for the study of mechanisms involved in motor neuron survival, degeneration and regeneration, volatile anesthetic-induced immobility, motor neuron disorders such as amyotrophic lateral sclerosis or spinal muscular atrophy as well as in spinal cord injury. Embryonic spinal cord motor neurons derived from rats have been successfully cultured; unfortunately, the culture of adult motor neurons has been problematic due to their short-term survival. Recently, by using a cocktail of target-derived factors, neurotrophins (brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor) and a permeable cyclic adenosine monophosphate analog, we have established a reproducible protocol for long-term cultures of healthy and functional adult motor neurons (Exp Neurol 220:303-315, 2009). Here, we now describe in detail the steps that we used for the optimization of the process of isolation and maintenance of adult rat ventral horn motor neurons in vitro.

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Effects of Neurotoxic or Pro-regenerative Agents on Motor and Sensory Neurite Outgrowth in Spinal Cord Organotypic Slices and DRG Explants in Culture

et al. 2021

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Muscle-conditioned media and cAMP promote survival and neurite outgrowth of adult spinal cord motor neurons

Cited by 22 publications

References 77 publications

Two familial ALS proteins function in prevention/repair of transcription-associated DNA damage

Two familial ALS proteins function in prevention/repair of transcription-associated DNA damage

Preparation of Adult Spinal Cord Motor Neuron Cultures Under Serum-Free Conditions

Effects of Neurotoxic or Pro-regenerative Agents on Motor and Sensory Neurite Outgrowth in Spinal Cord Organotypic Slices and DRG Explants in Culture

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