Stress alters murine hair growth, depending on substance P-mediated neurogenic inflammation and nerve growth factor (NGF), a key modulator of hair growth termination (catagen induction). Whether this is of any relevance in human hair follicles (HFs) is completely unclear. Therefore, we have investigated the effects of substance P, the central cutaneous prototypic stress-associated neuropeptide, on normal, growing human scalp HFs in organ culture. We show that these prominently expressed substance P receptor (NK1) at the gene and protein level. Organcultured HFs responded to substance P by premature catagen development, down-regulation of NK1, and up-regulation of neutral endopeptidase (degrades substance P). This was accompanied by mast cell degranulation in the HF connective tissue sheath , indicating neurogenic inflammation. Substance P down-regulated immunoreactivity for the growthpromoting NGF receptor (TrkA) , whereas it up-regulated NGF and its apoptosis-and catagen-promoting receptor (p75NTR). In addition , MHC class I and 2-microglobulin immunoreactivity were up-regulated and detected ectopically, indicating collapse of the HF immune privilege. In conclusion, we present a simplistic, but instructive, organ culture assay to demonstrate sensitivity of the human HF to key skin stress mediators. The data obtained therewith allow one to sketch the first evidence-based biological explanation for how stress may trigger or aggravate telogen effluvium and alopecia areata. (Am J Pathol
The peripheral nervous system comprises the autonomic and sensory (afferent) nervous systems. Major advances in our understanding of the autonomic and sensory transmission and function include the recognition of the phenotypic expression of a variety of transmitters and modulators that often coexist in individual neurons, the concept of co-transmission and chemical coding, the evidence for local effector functions of primary afferent nerves, and the discovery of plasticity of both the autonomic and the sensory nervous system during development, aging, diseases states, and inflammation. Co-transmission or plurichemical transmission, which indicates the release of more than one chemical messenger from the same neuron, enables autonomic and sensory neurons to exert a fine and highly regulated control of various functions such as circulation and immune response. The concept of chemical coding, in which the combination of transmitters/modulators is established, allows the identification of functional classes of neurons with their projections and targets. In addition to transmitters and modulators, autonomic and sensory neurons express multiple receptors, including G-proteincoupled and ion-gated receptors, further supporting the complexity of autonomic and sensory transmission and function. Autonomic neurons regulate the internal environment and maintain multiple homeostatic functions, and sensory neurons act as receptive structures that activate their targets in response to stimulation but also exert effector functions including the control of blood flow and vascular permeability, maintenance of mineralized tissue, and regulation of gene expression. Neurophysiology of painThe nociceptive system supports two sensory functions, pain and itch. Itch has often been regarded as a minor form of pain. Recently, it has been shown, however, that the pruritic system is supported by its own peripheral and central neuronal pathways which are closely associated, although antagonistic in some POMC processing in human melanocytes has been widely documented, and the a-MSH/MC1R/cAMP cascade has been implicated in the control of pigmentation. Only very recently, a role of b-endorphin, one cleavage product of b-LPH, has been demonstrated to influence melanocyte growth, dendricity and melanin biosynthesis via the m-opiate receptor. However, much earlier, it was shown that b-MSH, the other cleavage product of b-LPH, controls melanogenesis and melanin transfer in amphibians. To date, a specific receptor for b-MSH has not been identified. Earlier POMC processing has been found in melanosomes. Therefore, an MC1R-independent role of a-MSH was postulated and demonstrated in control of 6-tetrahydrobiopterin (6BH 4 )inhibited tyrosinase. Utilizing the depigmentation disorder vitiligo, we were now able to follow the fate of epidermal POMC processing in the presence of mM levels of hydrogen peroxide (H 2 O 2 ). In vitiligo epidermal PC2 and 7B2 protein expression is increased, whereas a-MSH, b-MSH and b-endorphin are significantly decreased. Analys...
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