Insulin and IGF receptor signalling in neural-stem-cell homeostasis

Abstract

Neural stem cells (NSCs) are found in two regions in the adult brain: the subgranular zone (SGZ) in the hippocampal dentate gyrus and the subventricular zone (SVZ) adjacent to the lateral ventricles. Similarly to other somatic stem cells, adult NSCs are found within specialized niches that are organized to facilitate NSC self-renewal. Alterations in stem-cell homeostasis can contribute to the consequences of neurodegenerative diseases, healthy ageing and tissue repair after damage. Insulin and the insulin-like growth factors (IGFs) function in stem-cell homeostasis across species. Studies in the mammalian central nervous system support essential roles for IGF and/or insulin signalling in NSC self-renewal, neurogenesis, cognition and sensory function through distinct ligand–receptor interactions. IGF-II is of particular interest as a result of its production by the choroid plexus and presence in cerebrospinal fluid (CSF). CSF regulates and supports the development, division and migration of cells in the adult brain and is required for NSC maintenance. In this Review, we discuss emerging data on the functions of IGF-II and IGF and/or insulin receptor signalling in the context of NSC regulation in the SVZ and SGZ. We also propose a model for IGF-II in which the choroid plexus is a major component of the NSC niche.

Compounds of the sphingomyelin-ceramide-glycosphingolipid pathways as secondary messenger molecules: new targets for novel therapies for fatty liver disease and insulin resistance

“…Dietary sea cucumber cerebroside (SCC) extracted from Acaudina molpadioides attenuated hepatic steatosis via inhibition of hepatic lipogenic gene expression and enzyme activity, and enhancement of triglyceride secretion from the liver (157,184,188). SCC inhibited hepatic lipogenic enzymes, including fatty acid synthase, malic enzyme (ME), and glucose-6-phosphatedehydrogenase (G6PDH).…”

Peripherally derived FGF21 promotes remyelination in the central nervous system

“…However, OPC proliferation increases in proximity to demyelinating lesions (17), which are often characterized by vascular barrier disruption (18). In addition, some of the cells in the CNS express peripheralhormone receptors, such as the insulin and mineralocorticoid receptors, which regulate neurogenesis in the adult CNS (19,20). Although the role of vascular barrier disruption in CNS regeneration has not yet been clarified, we hypothesized that vascular barrier disruption mediated by CNS injury induces the leakage of circulating factors into the CNS, resulting in remyelination.…”

Sirtuin-2 inhibition affects hippocampal functions and sodium butyrate ameliorates the reduction in novel object memory, cell proliferation, and neuroblast differentiation

“…In addition, Chen et al [14] found no effect of SIRT2 inhibition on brain injury such as amyotrophic lateral sclerosis and ischemic stroke. SIRT2 is closely related to AKT pathway in insulin as well as growth factor-responsive cells [15], and insulin receptor and growth factor receptors are highly expressed in the hippocampus [1617]. In contrast, HDAC inhibitors manipulate the epigenome and affects the expression of only 2% of mammalian genes [18].…”