Hyperactivation of sympathetic nerves drives depletion of melanocyte stem cells

Abstract

Stress is an out of the norm state caused by emotional or physical insults. While chronic stress is considered harmful, acute stress is thought to cause transient and reversible changes essential for fight or flight. Stress has been anecdotally associated with hair greying, but scientific evidence linking the two is scant. Here, using mouse stress models, we found that acute stress leads to hair greying through rapid depletion of melanocyte stem cells (MeSCs). Combining adrenalectomy, denervation, chemogenetics, cell ablation, and MeSC-specific adrenergic receptor knockout, we found that stress-induced MeSC loss is independent of the immune attack or adrenal hormones. Instead, hair greying results from activation of the sympathetic nervous system that innervates the MeSC niche. Upon stress, sympathetic nerve activation leads to burst release of the neurotransmitter norepinephrine, which acts directly on MeSCs. Norepinephrine drives quiescent MeSCs to proliferate rapidly, followed by migration and differentiation, leading to their permanent depletion from the niche. Transient suppression of MeSC proliferation with topical application of cell cycle inhibitors rescues stress-induced hair greying. Our studies demonstrate that stress-induced neuronal activity can be an upstream trigger that forces stem cells out of quiescence, and suggest that acute stress stimuli can be more detrimental than anticipated by causing rapid and irreversible loss of somatic stem cells.

Neural innervation as a potential trigger of morphological color change and sexual dimorphism in cichlid fish

“…morphological color change) by triggering remodeling of the cytoskeleton 74 , apoptosis of chromatophores 74,75 , as well as proliferation of chromatophores and changes in pigment synthesis 76 . Very recently, increased neural signaling has been even linked to the depletion of melanocyte stem cell pools leading to hair greying in humans 77 , which supports an evolutionary conserved link between the nervous system and pigment cells.…”

Dietary <i>Eriodictyon angustifolium</i> Tea Supports Prevention of Hair Graying by Reducing DNA Damage in CD34+ Hair Follicular Keratinocyte Stem Cells

“…13) Furthermore, sterubin, luteolin, and HGK from EaT have the potential to promote regeneration of de novo pigmented black hair after skin wounding. 18) It has been reported that noradrenaline from sympathetic nerve terminals mediates the effect of stress on MSC. 19) Our results suggest that flavonoids from EaT contributed to maintaining the niche function of HFKSC against X-ray-induced damage, thus preventing X-ray-induced hair graying (Fig.…”

“…18) It has been reported that noradrenaline from sympathetic nerve terminals mediates the effect of stress on MSC. 19) Our results suggest that flavonoids from EaT contributed to maintaining the niche function of HFKSC against X-ray-induced damage, thus preventing X-ray-induced hair graying (Fig. 2).…”

On the Potential Role of the Neural Crest Cells in Integrating Pigmentation Into Behavioral and Physiological Syndromes

“…However, the potential implication of catecholamines and the sympatho-adrenal system in explaining why MbC associates to stress response deserves further attention, considering also the potential interactions with the hypothalamus-pituitary-adrenocortical system (e.g., the adrenal medulla may regulate hormone secretion by the adrenal cortex and vice versa: Gallo-Payet et al, 1987;Kvetnansky et al, 2009). The fact that catecholamines can induce color changes in vertebrates (Bagnara and Matsumoto, 2007;Zhang et al, 2020) increases the interest of investigating their role in linking coloration and stress response.…”