The Biology and Genomics of Human Hair Follicles: A Focus on Androgenetic Alopecia.

Androgenetic alopecia is a highly prevalent condition mainly affecting men. This complex trait is related to aging and genetics; however, multiple other factors, for example, lifestyle, are also involved. Despite its prevalence, the underlying biology of androgenetic alopecia remains elusive, and thus advances in its treatment have been hindered. Herein, we review the functional anatomy of hair follicles and the cell signaling events that play a role in follicle cycling. We also discuss the pathology of androgenetic alopecia and the known molecular mechanisms underlying this condition. Additionally, we describe studies comparing the transcriptional differences in hair follicles between balding and non-balding scalp regions. Given the genetic contribution, we also discuss the most significant risk variants found to be associated with androgenetic alopecia. A more comprehensive understanding of this pathology may be generated through using multi-omics approaches.

Potential effects of cannabidiol as a wake-promoting agent.

Over the last decades, the scientific interest in chemistry and pharmacology of cannabinoids has increased. Most attention has focused on ∆(9)-tetrahydrocannabinol (∆(9)-THC) as it is the psychoactive constituent of Cannabis sativa (C. sativa). However, in previous years, the focus of interest in the second plant constituent with non-psychotropic properties, cannabidiol (CBD) has been enhanced. Recently, several groups have investigated the pharmacological properties of CBD with significant findings; furthermore, this compound has raised promising pharmacological properties as a wake-inducing drug. In the current review, we will provide experimental evidence regarding the potential role of CBD as a wake-inducing drug.

Characterization of Mitogen-Activated Protein Kinase Expression in Nucleus Accumbens and Hippocampus of Rats Subjected to Food Selection in the Cafeteria Diet Protocol.

Obesity is a world-wide health problem that requires different experimental perspectives to understand the onset of this disease, including the neurobiological basis of food selection. From a molecular perspective, obesity has been related with activity of several endogenous molecules, including the mitogenactivated protein kinases (MAP-K). The aim of this study was to characterize MAP-K expression in hedonic and learning and memory brain-associated areas such as nucleus accumbens (AcbC) and hippocampus (HIPP) after food selection. We show that animals fed with cafeteria diet during 14 days displayed an increase in p38 MAP-K activity in AcbC if chose cheese. Conversely, a diminution was observed in animals that preferred chocolate in AcbC. Also, a decrease of p38 MAP-K phosphorylation was found in HIPP in rats that selected either cheese or chocolate. Our data demonstrate a putative role of MAP-K expression in food selection. These findings advance our understanding of neuromolecular basis engaged in obesity.

Sleep and neurochemical modulation by the nuclear peroxisome proliferator-activated receptor α (PPAR-α) in rat.

The peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear protein that plays an essential role in diverse neurobiological processes. However, the role of PPARα on the sleep modulation is unknown. Here, rats treated with an intrahypothalamic injection of Wy14643 (10µg/1µL; PPARα agonist) enhanced wakefulness and decreased slow wave sleep and rapid eye movement sleep whereas MK-886 (10µg/1µL; PPARα antagonist) promoted opposite effects. Moreover, Wy14643 increased dopamine, norepinephrine, serotonin, and adenosine contents collected from nucleus accumbens. The levels of these neurochemicals were diminished after MK-886 treatment. The current findings suggest that PPARα may participate in the sleep and neurochemical modulation.

Intrahypothalamic Administration of Modafinil Increases Expression of MAP-Kinase in Hypothalamus and Pons in Rats.

Modafinil (MOD) it has to be considered as a wake-inducing drug to treat sleep disorders such as excessive sleepiness in narcolepsy, shift-work disorder, and obstructive/sleep apnea syndrome. Current evidence suggests that MOD induces waking involving the dopamine D1 receptor. However, little is known regarding the molecular elements linked in the wake-promoting actions of MOD. Since the D1 receptor activates the mitogen-activated protein kinase (MAP-K) cascade, it raises the interesting possibility that effects of MOD would depend upon the activation of MAP-K. Here we tested the expression of MAP-K in hypothalamus as well as pons after the microinjection of MOD (10 or 20 µg/1 µL) in rats into anterior hypothalamus, a wake-inducing brain area. Intrahypothalamic injections of MOD promoted MAP-K phosphorylation in hypothalamus and pons. Taken together, these results suggest that the wake-inducing compound MOD promotes the MAP-K phosphorylation.

Brain molecules and appetite: the case of oleoylethanolamide.

The neurobiological mechanisms of feeding involve the activity of several brain areas as well as the engagement of endogenous compounds such as ghrelin, melanin-concentrating hormone, orexin, neuropeptide Y, leptin, vasoactive intestinal peptide, cholecystokinin, among others. Furthermore, the family of food-intake modulators has been enlarged due to the inclusion of lipids such as N-arachidonoylethanolamide (anandamide), as well as oleoylethanolamide (OEA). In this regard, the food-intake suppressing properties of OEA have been described since pharmacological administration of this compound induces anorexia. It has been suggested that satiety induced by OEA may be through the activation of peroxisome proliferator-activated receptor-α (PPAR-α), a ligand-activated transcription factor that modulates several pathways of lipid metabolism. The mechanism of action of OEA remains unknown, it has been suggested that the ingestion of dietary fat stimulates epithelial cells of the small intestine and promotes the synthesis and release of OEA. Upon its release, this lipid acts within the gut engaging sensory fibers of the vagus nerve to diminish food-intake. Here, recent advances in our understanding of the neurobiological role of OEA in modulation of feeding will be reviewed. Also, we highlight the emerging molecular mechanism of anorexia induced by OEA.

Basic sleep mechanisms: an integrative review.

Regulation of the sleep-waking cycle is complex and involves diverse brain circuits and molecules. On one hand, an interplay among many neuroanatomical and neurochemical systems including acetylcholine, dopamine, noradrenaline, serotonin, histamine, and hypocretin has been shown to control the waking state. On the other hand the sleep-onset is governed by the activity of sleep-promoting neurons placed in the anterior hypothalamus that utilize GABA to inhibit wake-promoting regions. Moreover, brainstem regions inhibited during wakefulness (W) and slow wave sleeps (SWS) become active during rapid eye movement (REM) sleep. Further complexity has been introduced by the recognition of sleep-promoting molecules that accumulate in the brain in prolonged W as well as the physiological role of gene expression during sleep. The sleep-wake cycle is currently undergoing intense research with many new findings leading to new paradigms concerning sleep regulation, brain organization and sleep function. This review provides a broader understanding of our present knowledge in the field of sleep research.