Sonic hedgehog pathway activation increases mitochondrial abundance and activity in hippocampal neurons

Abstract

Activation of the Sonic hedgehog signaling pathway affects multiple aspects of mitochondria in hippocampal neurons. It increases mitochondrial mass significantly, reduces fission, and promotes elongation. It also protects neurons against stress.

Hedgehog Signaling Modulates Glial Proteostasis and Lifespan

“…All molecular players described here are conserved; the vertebrate counterpart of Drosophila Hh, Shh, is also expressed in mouse adult neurons, and glial cells respond to this signal (Garcia et al, 2010;Farmer et al, 2016). Because the activation of Shh signaling protects against diverse neurotoxins such as Ab peptide in vitro, (Ab 1-42) (Yao et al, 2017), our study suggests that Hh signaling in glia may ameliorate age-related neurodegenerative diseases caused by aberrant protein aggregation as well as prolong healthspan and fitness.…”

“…Due to its role as a neuroprotective factor, it is hypothesized that Shh may be implicated in alleviating age-related neurodegenerative disease Yao et al, 2017). For instance, in cultured rat hippocampal neurons, Shh signaling confers protection against neurotoxins such as the amyloid beta peptide (Ab 1-42) (Yao et al, 2017). However, the mechanism by which Shh exerts its protective function in this experimental paradigm has not yet been elucidated.…”

Purine Biosynthesis Enzymes in Hippocampal Neurons

“…Cultures of hippocampal neurons were prepared from embryonic day 18 rat brains as described (Mattson et al 1989; Kaech and Banker 2006; Yao et al 2017). Dissociated neurons were plated at a density of ~100 cells/mm 2 .…”

Hedgehog Signalling Modulates Glial Proteostasis and Lifespan

“…All molecular players described here are conserved; the vertebrate counterpart of Drosophila Hh, Shh, is also expressed in mouse adult neurons and glial cells respond to this signal (Garcia et al, 2010, Farmer et al, 2016. Since the activation of Shh signalling protects against diverse neurotoxins such as amyloid beta peptide in vitro (Yao et al, 2017), our study suggests that Hh signaling in glia may ameliorate age-related neurodegenerative diseases caused by aberrant protein aggregation as well as prolong healthspan and fitness in mammals.…”

“…Due to its role as a neuroprotective factor, it is hypothesised that Shh may be implicated in alleviating age-related neurodegenerative disease Yao et al, 2017). For instance in cultured rat hippocampal neurons, Shh signalling confers protection against neurotoxins such as the Amyloid beta peptide (Ab 1-42; Yao et al, 2017). However the mechanism by which Shh exerts its protective function in a live organism has not been explored.…”