Edited by Luke O'NeillAlongside the rapid growth in aging populations worldwide, prevention and therapy for age-related memory decline and dementia are in great demand to maintain a long, healthy life. Here we found that iso-␣-acids, hop-derived bitter compounds in beer, enhance microglial phagocytosis and suppress inflammation via activation of the peroxisome proliferator-activated receptor ␥. In normal mice, oral administration of iso-␣-acids led to a significant increase both in CD11b and CD206 doublepositive anti-inflammatory type microglia (p < 0.05) and in microglial phagocytosis in the brain. In Alzheimer's model 5xFAD mice, oral administration of iso-␣-acids resulted in a 21% reduction in amyloid ␤ in the cerebral cortex as observed by immunohistochemical analysis, a significant reduction in inflammatory cytokines such as IL-1␤ and chemokines including macrophage inflammatory protein-1␣ in the cerebral cortex (p < 0.05) and a significant improvement in a novel object recognition test (p < 0.05), as compared with control-fed 5xFAD mice. The differences in iso-␣-acid-fed mice were due to the induction of microglia to an anti-inflammatory phenotype. The present study is the first to report that amyloid ␤ deposition and inflammation are suppressed in a mouse model of Alzheimer's disease by a single component, iso-␣-acids, via the regulation of microglial activation. The suppression of neuroinflammation and improvement in cognitive function suggests that iso-␣-acids contained in beer may be useful for the prevention of dementia.

The authors herein describe the morphologic and immunohistochemical features of normal Merkel cells as well as the clinicopathologic findings of Merkel cell carcinoma in cats. Merkel cells were characterized as vacuolated clear cells and were individually located in the epidermal basal layer of all regions examined. Clusters of Merkel cells were often observed adjacent to the sinus hair of the face and carpus. Immunohistochemically, Merkel cells were positive for cytokeratin (CK) 20, CK18, p63, neuron-specific enolase, synaptophysin, and protein gene product 9.5. Merkel cell carcinoma was detected as a solitary cutaneous mass in 3 aged cats (13 to 16 years old). On cytology, large lymphocyte-like cells were observed in all cases. Histologic examinations of surgically resected tumors revealed nests of round cells separated by various amounts of a fibrous stroma. Tumor cells were commonly immunopositive for CK20, CK18, p63, neuron-specific enolase, and synaptophysin, representing the characteristics of normal Merkel cells. 29 Merkel cells are located in the hair discs (Haarscheiben), hair follicles, interfollicular epidermis, and glabrous skin in humans. 20,21 However, a previous study reported that Merkel cells were absent in hair follicles in the body skin of mice and present only in the epidermal hair discs and whisker hair follicles.20 Most Merkel cells possess synaptic connections with the enlarged terminal endings of myelinated sensory nerve fibers. Neurotransmitters or neuromodulators are secreted from Merkel cells through exocytosis in response to mechanical stimuli to the skin, thereby suggesting a function of Merkel cells as a mechanoreceptor of tactile sensation. 10,12 Difficulties have been associated with identifying Merkel cells on routine hematoxylin and eosin (HE)-stained sections. 20Merkel cells express various neuropeptides and neuroendocrine markers, such as neuron-specific enolase (NSE), chromogranin A, synaptophysin, and protein gene product 9.5 (PGP9.5) in humans, making them identifiable by immunohistochemistry. 7,9,17,24 Cytokeratin (CK) 20 is assumed to be the most specific marker for Merkel cells in the skin of humans and mice. 5In humans, CK20-positive Merkel cells are distributed in the palms and hairy skin of embryos and fetuses and in the ventral midline of adults (the incision line of a routine autopsy). 14,20 To the best of our knowledge, the presence and distribution of CK20-positive Merkel cells have not yet been examined in normal cat skin.Merkel cell carcinoma is a rare cutaneous tumor showing both epithelial and neuroendocrine differentiation. Although Merkel cell carcinoma is considered to arise from Merkel cells, recent findings indicated that primitive epidermal stem cells or early B cells were the origin of Merkel cell carcinoma. 13,27,30 Only 3 cases of feline Merkel cell carcinoma have been reported to date and were diagnosed by examining biopsy samples. Two cases were accompanied by pulmonary and lymph node metastases showing malignant behaviors, 22,23 while the

Uteri from 50 four-toed hedgehogs ( Atelerix albiventris) with clinical signs of uterine disease were histopathologically examined. Sixteen animals (32%) were diagnosed with endometrial hyperplasia, 7 animals (14%) were diagnosed with endometrial polyp, and 27 animals (54%) were diagnosed with endometrial neoplasia. The mean ages of the animals with endometrial hyperplasia, polyp, and neoplasia were 28.7 months, 29.4 months, and 25.2 months, respectively. The neoplasms were classified into 7 endometrial mixed tumors, 12 endometrial stromal nodules, and 8 endometrial stromal sarcomas. However, the endometrial stromal nodules and endometrial stromal sarcomas often developed within or were contiguous with an endometrial polyp or mixed tumor. Interestingly, the stromal tumors and the stromal components of the endometrial polyp and mixed tumor displayed extraendometrial differentiation (eg, into adipocytes, granular cells, smooth muscle cells, and osteoid tissue). The endometrial stromal sarcomas exhibited severe cellular atypia and invaded subendometrial tissue. Immunohistochemical examinations demonstrated that the stromal cells of the hyperplastic lesions as well as the neoplastic lesions were positive for CD10, the progesterone receptor, and Wilms tumor 1. The four-toed hedgehog develops unique uterine neoplasms that are mainly composed of endometrial stromal cells and probably arise from endometrial polyps and/or mixed tumors.

A 10-year-old mixed breed dog was presented with a 0.8 cm diameter mass below the left eye region. The mass was surgically removed and processed for histopathological examination. Microscopically, tumor cells proliferated in small lobules, nests and cords, and the tumor parenchyma was separated by desmoplastic stroma. Majority of the tumor cells were periodic acid-Schiff (PAS)-positive, and the desmoplastic stroma was densely collagenous and mucinous. Immunohistochemical results showed that the tumor cells were diffusely positive for cytokeratin 15, cytokeratin 19 and CD 34, while cytokeratin 8 reactivity was limited to the tumor cells proliferating in cords. Few tumor cells were positive for nestin. Based on the histopathological findings, the tumor was diagnosed as desmoplastic tricholemmoma.

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