Brain allopregnanolone induces marked scratching behaviour in diet-induced atopic dermatitis mouse model
| Autor: | Masanori Fujii, Erika Asano, Takanori Nakayama, Susumu Ohya, Takeshi Nabe, Sayaka Ohgami, Takahiro Toda |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male endocrine system Neuroactive steroid Eczema lcsh:Medicine chemical and pharmacologic phenomena Pregnanolone Pharmacology Article Dermatitis Atopic Atopy 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine immune system diseases medicine Animals lcsh:Science Multidisciplinary Behavior Animal business.industry Pruritus lcsh:R Allopregnanolone Brain hemic and immune systems Atopic dermatitis Scratching medicine.disease Grooming Diet Disease Models Animal 030104 developmental biology surgical procedures operative chemistry Systemic administration Itching lcsh:Q Serotonin medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-11 (2019) |
| ISSN: | 2045-2322 |
| Popis: | Allopregnanolone (ALLO) is a neurosteroid produced in the brain, but so far, no study has explored its link with itching. Herein, we used a diet-induced atopic dermatitis mouse model to examine whether exogenously administered and endogenously produced ALLO contribute to inducing scratching. Systemic administration of ALLO elicited robust scratching in the atopic dermatitis model, while it did not affect spontaneous and pruritogen-induced scratching in normal mice. ALLO caused scratching when administered intracisternally, but not when administered intrathecally or intradermally, suggesting the involvement of supraspinal mechanisms. Pharmacological analyses suggested that both γ-aminobutyric acid type A receptor activation and serotonin type 3 receptor inhibition were involved in ALLO-induced scratching. We next examined whether endogenously produced ALLO is involved in ethanol-induced scratching in atopic dermatitis mice, because ethanol administration increases ALLO in rodent brain. Acute ethanol administration increased brain ALLO levels, which coincided with increased scratching. Pre-treatment with finasteride, a synthetic ALLO inhibitor, suppressed ethanol-induced scratching and ALLO production in the brain. Collectively, our results demonstrated for the first time that ALLO administration caused marked scratching in atopic dermatitis mice, and ethanol-induced scratching may be mediated through endogenously produced brain ALLO. |
| Databáze: | OpenAIRE |
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