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Cell Aug 2020Piloerection (goosebumps) requires concerted actions of the hair follicle, the arrector pili muscle (APM), and the sympathetic nerve, providing a model to study...
Piloerection (goosebumps) requires concerted actions of the hair follicle, the arrector pili muscle (APM), and the sympathetic nerve, providing a model to study interactions across epithelium, mesenchyme, and nerves. Here, we show that APMs and sympathetic nerves form a dual-component niche to modulate hair follicle stem cell (HFSC) activity. Sympathetic nerves form synapse-like structures with HFSCs and regulate HFSCs through norepinephrine, whereas APMs maintain sympathetic innervation to HFSCs. Without norepinephrine signaling, HFSCs enter deep quiescence by down-regulating the cell cycle and metabolism while up-regulating quiescence regulators Foxp1 and Fgf18. During development, HFSC progeny secretes Sonic Hedgehog (SHH) to direct the formation of this APM-sympathetic nerve niche, which in turn controls hair follicle regeneration in adults. Our results reveal a reciprocal interdependence between a regenerative tissue and its niche at different stages and demonstrate sympathetic nerves can modulate stem cells through synapse-like connections and neurotransmitters to couple tissue production with demands.
Topics: Accessory Nerve; Animals; Cell Cycle; Cold Temperature; Female; Fibroblast Growth Factors; Forkhead Transcription Factors; Gene Expression Profiling; Hair; Hair Follicle; Hedgehog Proteins; Humans; Male; Mice; Mice, Inbred C57BL; Norepinephrine; Piloerection; RNA-Seq; Receptors, Adrenergic, beta-2; Repressor Proteins; Signal Transduction; Smoothened Receptor; Stem Cell Niche; Stem Cells; Sympathetic Nervous System; Synapses
PubMed: 32679029
DOI: 10.1016/j.cell.2020.06.031 -
Nature Materials Apr 2024Microactuators provide controllable driving forces for precise positioning, manipulation and operation at the microscale. Development of microactuators using active...
Microactuators provide controllable driving forces for precise positioning, manipulation and operation at the microscale. Development of microactuators using active materials is often hampered by their fabrication complexity and limited motion at small scales. Here we report light-fuelled artificial goosebumps to actuate passive microstructures, inspired by the natural reaction of hair bristling (piloerection) on biological skin. We use light-responsive liquid crystal elastomers as the responsive artificial skin to move three-dimensionally printed passive polymer microstructures. When exposed to a programmable femtosecond laser, the liquid crystal elastomer skin generates localized artificial goosebumps, resulting in precise actuation of the surrounding microstructures. Such microactuation can tilt micro-mirrors for the controlled manipulation of light reflection and disassemble capillary-force-induced self-assembled microstructures globally and locally. We demonstrate the potential application of the proposed microactuation system for information storage. This methodology provides precise, localized and controllable manipulation of microstructures, opening new possibilities for the development of programmable micromachines.
PubMed: 38336868
DOI: 10.1038/s41563-024-01810-6 -
International Journal of... Sep 2022This paper provides an accessible review of the biological and psychological evidence to guide new and experienced researchers in the study of emotional piloerection in... (Review)
Review
This paper provides an accessible review of the biological and psychological evidence to guide new and experienced researchers in the study of emotional piloerection in humans. A limited number of studies have attempted to examine the physiological and emotional correlates of piloerection in humans. However, no review has attempted to collate this evidence to guide the field as it moves forward. We first discuss the mechanisms and function of non-emotional and emotional piloerection in humans and animals. We discuss the biological foundations of piloerection as a means to understand the similarities and differences between emotional and non-emotional piloerection. We then present a systematic qualitative review (k = 24) in which we examine the physiological correlates of emotional piloerection. The analysis revealed that indices of sympathetic activation are abundant, suggesting emotional piloerection occurs with increased (phasic) skin conductance and heart rate. Measures of parasympathetic activation are lacking and no definite conclusions can be drawn. Additionally, several studies examined self-reported emotional correlates, and these correlates are discussed in light of several possible theoretical explanations for emotional piloerection. Finally, we provide an overview of the methodological possibilities available for the study of piloerection and we highlight some pressing questions researchers may wish to answer in future studies.
Topics: Animals; Emotions; Heart Rate; Humans; Piloerection
PubMed: 35764195
DOI: 10.1016/j.ijpsycho.2022.06.010 -
International Journal of Molecular... Sep 2023Matricellular proteins are secreted extracellular proteins that bear no primary structural functions but play crucial roles in tissue remodeling during development,... (Review)
Review
Matricellular proteins are secreted extracellular proteins that bear no primary structural functions but play crucial roles in tissue remodeling during development, homeostasis, and aging. Despite their low expression after birth, matricellular proteins within skin compartments support the structural function of many extracellular matrix proteins, such as collagens. In this review, we summarize the function of matricellular proteins in skin stem cell niches that influence stem cells' fate and self-renewal ability. In the epidermal stem cell niche, fibulin 7 promotes epidermal stem cells' heterogeneity and fitness into old age, and the transforming growth factor-β-induced protein ig-h3 (TGFBI)-enhances epidermal stem cell growth and wound healing. In the hair follicle stem cell niche, matricellular proteins such as periostin, tenascin C, SPARC, fibulin 1, CCN2, and R-Spondin 2 and 3 modulate stem cell activity during the hair cycle and may stabilize arrector pili muscle attachment to the hair follicle during piloerections (goosebumps). In skin wound healing, matricellular proteins are upregulated, and their functions have been examined in various gain-and-loss-of-function studies. However, much remains unknown concerning whether these proteins modulate skin stem cell behavior, plasticity, or cell-cell communications during wound healing and aging, leaving a new avenue for future studies.
Topics: Skin Aging; Skin; Epidermis; Homeostasis
PubMed: 37762584
DOI: 10.3390/ijms241814274 -
Frontiers in Neuroscience 2020The volitional control of piloerection has been previously reported in a small subset of individuals. Although this ability may be useful to study the mechanism...
The volitional control of piloerection has been previously reported in a small subset of individuals. Although this ability may be useful to study the mechanism underlying piloerection, there is little existing research on this ability, neither objective evidence at a group-level, nor information about its stability under experimental constraints. The present study aimed to validate existing findings of voluntarily generated piloerection (VGP) and to examine its potential contribution to neuroscientific research based on objective evidence of this ability. In Study 1, to confirm the characteristics of VGP reported in previous studies and identify individuals with VGP capability, an online survey of VGP candidates was conducted. In Study 2, 18 VGP holders participated in a mail-based piloerection measurement experiment, and the nature of VGP was examined based on the objective data obtained by image-based analysis (GooseLab). Study 1 largely confirmed the characteristics of VGP reported in previous studies, and Study 2 demonstrated VGP at a group-level and provided information about the temporal characteristics of this ability, which supports the utility of VGP in neuroscientific research. For some participants, VGP appeared to be emotionally promoted, which suggests that VGP has some relationship with the emotional nature of involuntary piloerection. Although the studies did not tightly control the environment in which VGP was elicited, the findings nonetheless demonstrate the possible contribution of VGP to elucidating the mechanism of involuntary emotional piloerection and the neural basis of piloerection itself.
PubMed: 32581701
DOI: 10.3389/fnins.2020.00590 -
Behavioural Pharmacology Apr 2022Newly emerging synthetic cannabinoid compounds continue to be found in the designer drug market. They are often targeted as a 'legal high' alternative to traditional...
Newly emerging synthetic cannabinoid compounds continue to be found in the designer drug market. They are often targeted as a 'legal high' alternative to traditional cannabinoids via 'darknet' markets and their increased potency and efficacy are becoming a growing concern internationally. The purpose of this study was to determine whether 4-CN-CUMYL-BUTINACA, 4F-MDMB-BINACA, 5F-AEB, 5F-CUMYL-P7AICA and EMB-FUBINACA exhibited similar behavioral effects as Δ9-tetrahydrocannabinol (Δ9-THC). Locomotor activity was assessed in an open-field assay using Swiss-Webster mice. Male Sprague-Dawley rats were trained to discriminate between intraperitoneal injections of Δ9-THC (3 mg/kg) and vehicle. Following successful training, substitution tests for 4-CN-CUMYL-BUTINACA, 4F-MDMB-BINACA, 5F-AEB, 5F-CUMYL-P7AICA and EMB-FUBINACA were conducted. All of the test compounds decreased locomotor activity. 4-CN-CUMYL-BUTINACA (ED50 = 0.26 mg/kg), 4F-MDMB-BINACA (ED50 = 0.019 mg/kg), 5F-CUMYL-P7AICA (ED50 = 0.13 mg/kg) and EMB-FUBINACA (ED50 = 0.13 mg/kg) each fully substituted for the discriminative stimulus effects of the training dose of Δ9-THC, whereas 5F-AEB produced only a maximum of 67% drug-appropriate responding at 0.5 mg/kg. Higher doses produced piloerection, exophthalmos and convulsions. 4-CN-CUMYL-BUTINACA, 4F-MDMB-BINACA, 5F-CUMYL-P7AICA and EMB-FUBINACA are likely to produce similar subjective effects in humans as those produced by abused synthetic cannabinoids, and may therefore share similar abuse liability. In contrast, 5F-AEB may have a reduced abuse liability given its weaker THC-like discriminative stimulus effects but maybe more dangerous due to the adverse effects observed at doses needed to produce discriminative stimulus effects.
Topics: Animals; Cannabinoids; Dronabinol; Indazoles; Locomotion; Male; Mice; Rats; Rats, Sprague-Dawley
PubMed: 33595956
DOI: 10.1097/FBP.0000000000000618 -
Frontiers in Neurology 2019The human skin is a highly specialized organ for receiving sensory information but also to preserve the body's homeostasis. These functions are mediated by cutaneous... (Review)
Review
The human skin is a highly specialized organ for receiving sensory information but also to preserve the body's homeostasis. These functions are mediated by cutaneous small nerve fibers which display a complex anatomical architecture and are commonly classified into cutaneous A-beta, A-delta and C-fibers based on their diameter, myelinization, and velocity of conduction of action potentials. Knowledge on structure and function of these nerve fibers is relevant as they are selectively targeted by various autonomic neuropathies such as diabetic neuropathy or Parkinson's disease. Functional integrity of autonomic skin nerve fibers can be assessed by quantitative analysis of cutaneous responses to local pharmacological induction of axon reflex responses which result in dilation of cutaneous vessels, sweating, or piloerection depending on the agent used to stimulate this neurogenic response. Sensory fibers can be assessed using quantitative sensory test. Complementing these functional assessments, immunohistochemical staining of superficial skin biopsies allow analysis of structural integrity of cutaneous nerve fibers, a technique which has gained attention due to its capacity of detecting pathogenic depositions of alpha-synuclein in patients with Parkinson's disease. Here, we reviewed the current literature on the anatomy and functional pathways of the cutaneous autonomic nervous system as well as diagnostic techniques to assess its functional and structural integrity.
PubMed: 31551921
DOI: 10.3389/fneur.2019.00970 -
IBRO Neuroscience Reports Dec 2022Alcoholic neuropathy (AN), a debilitating condition that mainly affects chronic alcohol drinkers, is thought to cause lesions in the peripheral nervous system leading to...
Alcoholic neuropathy (AN), a debilitating condition that mainly affects chronic alcohol drinkers, is thought to cause lesions in the peripheral nervous system leading to sensory, autonomic, and motor dysfunctions. Despite many studies, the pathogenesis of these lesions is still not completely understood. We investigated few aspects on the development of alcohol-induced peripheral neuropathy, by assessing sensory, motor and autonomic functions, as well as stereological analysis of axonal fibers and myelin sheath of the sciatic nerve. Twelve male Wistar rats were divided into Control group and Alcohol group that was submitted to Two Bottle-Choice Paradigm of intermittent and voluntary alcohol solution intake (20%; v/v) during eight weeks. At the end of treatment, three different sensorium-motor tests were applied - Tactile Sensitivity, Thermal Sensitivity, and Functional Observational Battery (FOB). Quantitative morphometric analysis of sciatic nerve structures was performed by stereological method. Alcohol concentration in the blood was measured to analyze possible correlation between availability of alcohol in the blood and the magnitude of the peripheral nerve lesion. Our data showed a peripheral effect of chronic alcohol intake associated with hyperalgesia and a process of demyelination with a strong correlation with alcohol consumption. This process was associated with increased tactile sensitivity, with behavioral reflexes such as locomotor hyperactivity, changes in gait and balance, and autonomic reflexes such as piloerection.
PubMed: 36065406
DOI: 10.1016/j.ibneur.2022.08.004 -
Acta Medica (Hradec Kralove) 2022Organophosphorus compounds induce irreversible inhibition of acetylcholinesterase, which then produces clinically manifested muscarinic, nicotinic and central effects....
Organophosphorus compounds induce irreversible inhibition of acetylcholinesterase, which then produces clinically manifested muscarinic, nicotinic and central effects. The aim of the study was to analyse the clinical signs of acute paraoxon poisoning in rats and to determine the relationship between the intensity of signs of poisoning and the dose of paraoxon and/or the outcome of poisoning in rats. Animals were treated with either saline or atropine (10 mg/kg intramuscularly). The median subcutaneous lethal dose (LD50) of paraoxon was 0.33 mg/kg and protective ratio of atropine was 2.73. The presence and intensity of signs of poisoning in rats (dyspnoea, lacrimation, exophthalmos, fasciculations, tremor, ataxia, seizures, piloerection, stereotypic movements) were observed and recorded for 4 h after the injection of paraoxon. Intensity of these toxic phenomena was evaluated as: 0 - absent, 1 - mild/moderate, 2 - severe. Fasciculations, seizures and tremor were more intense at higher doses of paraoxon and in non-survivors. In unprotected rats piloerection occurred more often and was more intense at higher doses of paraoxon as well as in non-survivors. In atropine-protected rats, piloerection did not correlate with paraoxon dose or outcome of poisoning. The intensity of fasciculations and seizures were very strong prognostic parameters of the poisoning severity.
Topics: Acetylcholinesterase; Animals; Atropine; Fasciculation; Paraoxon; Rats; Seizures; Tremor
PubMed: 35793503
DOI: 10.14712/18059694.2022.10 -
Frontiers in Neurology 2022Late-onset epilepsy (LOE) has recently become a topic of intense research. Besides stroke, tumors, and dementia, autoimmune encephalitis (AE) has emerged as another...
INTRODUCTION
Late-onset epilepsy (LOE) has recently become a topic of intense research. Besides stroke, tumors, and dementia, autoimmune encephalitis (AE) has emerged as another possible cause of recurrent seizures in the elderly, and may account for a proportion of cases of LOE of unknown origin (LOEUO). This 24-h ambulatory electroencephalography (AEEG)-based study compared patients with LOEUO and AE to identify features suggestive of immune-mediated seizures in the elderly.
MATERIALS AND METHODS
We retrospectively reviewed 232 AEEG examinations performed in patients over 55 years with ≥6-month follow-up, and selected 21 subjects with AE and 25 subjects with LOEUO. Clinical charts and AEEG recordings were carefully analyzed.
RESULTS
Twenty-five patients with LOEUO (12 women, mean age at onset 67.9 years) and 21 AE subjects (8 women, mean age at onset 65.7 years) were enrolled. High-frequency seizures were reported in 20/21 AE and 7/25 LOEUO cases ( < 0.00001). Focal aware seizures were more common in AE (14/21 vs. 6/25, = 0.00058), whereas "isolated" focal-to-bilateral tonic-clonic seizures occurred in 5/25 patients with LOEUO only ( = 0.053). AE subjects reported ictal autonomic manifestations more frequently ( = 0.0033). Three-hundred-seventy and 24 seizures were recorded in 13/21 patients with AE and 3/25 patients with LOEUO, respectively ( = 0.0006). Interictal epileptiform discharges were observed in 70% of both groups, but their sleep activation was more common in AE ( = 0.06).
CONCLUSION
Our study shows that high-frequency focal seizures with autonomic manifestations should raise the suspicion of AE in the elderly with new-onset seizures. It also highlights the relevant contribution of AEEG, which might reduce the diagnostic delay and provide useful clues to recognize AE.
PubMed: 36034285
DOI: 10.3389/fneur.2022.924859