Abstract:
:Accumulating evidence suggests that neuroinflammatory processes are implicated in the initiation and progression of amyotrophic lateral sclerosis (ALS). Previous reports have demonstrated an increase in microgliosis and astrogliosis in the lumbar spinal cord of SOD1G93A transgenic mice before the onset of symptoms, a neuroinflammatory response which correlated with disease progression. Importantly, early stage homeostatic microglia enhanced motor neuron survival, while pro-inflammatory microglia were toxic to motor neurons in the SOD1G93A mice. Recent studies from our group have demonstrated that cromolyn sodium, an FDA approved compound, exerts neuroprotective effects in mouse models of Alzheimer's disease by altering microglial cell activation. Here, we tested the neuroprotective and anti-inflammatory effects of cromolyn sodium in the SOD1G93A mouse model of ALS. Our results indicate that cromolyn sodium treatment significantly delayed the onset of neurological symptoms, and improved deficits in PaGE performance in both male and female mice, however, there was only an effect on survival in female mice. Furthermore, there was a significant increase in motor neuron survival in the lumbar spinal cord as well as a significant decrease in the denervation of the neuromuscular junction of the tibialis anterior muscle in cromolyn treated transgenic SOD1G93A mice. Lastly, cromolyn treatment decreased the expression of pro-inflammatory cytokines/chemokines in the lumbar spinal cord and plasma and decreased mast cell degranulation in the tibialis anterior muscle of transgenic SOD1G93A mice. Together, these findings suggest that cromolyn sodium provides neuroprotection in the SOD1G93A mice by decreasing the inflammatory response.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Granucci EJ,Griciuc A,Mueller KA,Mills AN,Le H,Dios AM,McGinty D,Pereira J,Elmaleh D,Berry JD,Paganoni S,Cudkowicz ME,Tanzi RE,Sadri-Vakili Gdoi
10.1038/s41598-019-53982-wsubject
Has Abstractpub_date
2019-11-27 00:00:00pages
17728issue
1issn
2045-2322pii
10.1038/s41598-019-53982-wjournal_volume
9pub_type
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