Aspects of the narcolepsy-cataplexy syndrome in O/E3-null mutant mice.

Orexins (hypocretins) are peptide neurotransmitters produced by a small group of neurons located exclusively in the lateral hypothalamus (LH). Orexins modulate arousal, and as a result, have profound effects on feeding behavior and the sleep-wake cycle. Loss of orexin producing neurons leads to a narcoleptic phenotype, characterized by sudden transitions from vigilance to rapid eye movement (REM) sleep (direct transition to REM, DREM) observed in electroencephalogram (EEG) and electromyogram (EMG) recordings. In this study, we demonstrate that mice lacking the basic helix-loop-helix transcription factor O/E3 (also known as ebf2) have a decrease in orexin-producing cells in the LH, in addition to a severely impaired orexinergic innervation of the pons. These changes in the orexinergic circuit of O/E3-null animals induce a narcoleptic phenotype, similar to the one arising in orexin-deficient and orexin-ataxin-3 mice. Taken together, our results suggest that O/E3 plays a central role during the establishment of a functional orexinergic circuit by controlling the expression of essential hypothalamic neurotransmitter and the correct development of the nerve fibers arising from the hypothalamus. This is the first report regarding the narcolepsy-cataplexy syndrome in O/E3-null mice, which adds the importance of transcription factors in the regulation of neural subpopulations that control the sleep-wake cycle.

Epidermal Langerhans cells in the terrestrial turtle, Kinosternum integrum.

In mammalian epidermis, Langerhans cells (LC) are the only antigen-presenting dendritic cells that possess the ectoenzyme adenosine triphosphase (ATPase) and constitutively express class II molecules encoded by the major histocompatibility complex. Recently, we demonstrated the presence of LC in chicken epidermis. The aim of the present study is to demonstrate the presence of LC-like cells in turtle Kinosternum integrum, epidermis by light and ultrastructural ATPase histochemistry. ATPase-positive dendritic cells were observed in epidermal sheets whose maximum mean number was 192 cells/mm2. Electron microscopy for ATPase stained sections showed an electrondense precipitate in the plasma membrane of dendritic clear cells located among basal and suprabasal keratinocytes, ultrastructurally similar to LC. In serial sections, some dendritic cells showed LC (Birbeck) granules. The present study demonstrates for the first time ATPase-positive dendritic cells, morphologically similar to LC, in reptilian epidermis.

Ia antigens are expressed on ATPase-positive dendritic cells in chicken epidermis.

Langerhans cells (LC) are antigen-presenting dendritic cells located in mammalian epidermis and in other stratified epithelia. We recently demonstrated the presence of Langerhans-like cells in the epidermis of the chicken using ultrastructural histochemistry for adenosine triphosphatase (ATPase). The aim of the present study was to test whether ATPase-positive dendritic cells also express class II histocompatibility molecules (Ia antigens) encoded by the major histocompatibility complex (MHC), using a double staining technique, in separated chicken epidermal sheets. We concluded that the epidermal dendritic cells observed are the LC of the chicken, based on their morphology and spatial distribution, but mainly on the complete overlap for ATPase reaction and Ia antigen expression, these being reliable markers for the identification of mammalian LC.