Astrocytes with TDP-43 inclusions exhibit reduced noradrenergic cAMP and Ca²⁺ signaling and dysregulated cell metabolism.

ABSTRACT: Most cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have cytoplasmic inclusions of TAR DNA-binding protein 43 (TDP-43) in neurons and non-neuronal cells, including astrocytes, which metabolically support neurons with nutrients. Neuronal metabolism largely depends on the activation of the noradrenergic system releasing noradrenaline. Activation of astroglial adrenergic receptors with noradrenaline triggers cAMP and Ca²⁺ signaling and augments aerobic glycolysis with production of lactate, an important neuronal energy fuel. Astrocytes with cytoplasmic TDP-43 inclusions can cause motor neuron death, however, whether astroglial metabolism and metabolic support of neurons is altered in astrocytes with TDP-43 inclusions, is unclear. We measured lipid dr

SUBMITTER: Velebit J 

PROVIDER: S-EPMC7138839 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature