Perillyl alcohol reduces parasite sequestration and cerebrovascular dysfunction during experimental cerebral malaria.

Cerebral malaria (CM) is a severe immunovasculopathy which presents high mortality rate (15-20%), despite the availability of artemisinin-based therapy. More effective immunomodulatory and/or antiparasitic therapies are urgently needed. Experimental Cerebral Malaria (ECM) in mice is used to elucidate aspects involved in this pathology since manifests many of the neurological features of CM. In the present study, we evaluated the potential mechanisms involved in the protection afforded by perillyl alcohol (POH) in mouse strains susceptible to CM caused by Plasmodium berghei ANKA (PbA) infection through intranasal preventive treatment. Additionally, to evaluate the interaction of POH with the cerebral endothelium using an in vitro model of human brain endothelial cells (HBEC). Pharmacokinetic approaches demonstrated constant and prolonged levels of POH in the plasma and brain after a single intranasal dose. Treatment with POH effectively prevented vascular dysfunction. Furthermore, treatment with POH reduced the endothelial cell permeability and PbA s in the brain and spleen. Finally, POH treatment decreased the accumulation of macrophages and T and B cells in the spleen and downregulated the expression of endothelial adhesion molecules (ICAM-1, VCAM-1, and CD36) in the brain. POH is a potent monoterpene that prevents cerebrovascular dysfunction in vivo and in vitro, decreases parasite sequestration, and modulates different processes related to the activation, permeability, and integrity of the blood brain barrier (BBB), thereby preventing cerebral oedema and inflammatory infiltrates.

Ciliary melanin-concentrating hormone receptor 1 (MCHR1) is widely distributed in the murine CNS in a sex-independent manner.

Melanin-concentrating hormone (MCH) is a ubiquitous vertebrate neuropeptide predominantly synthesized by neurons of the diencephalon that can act through two G protein-coupled receptors, called MCHR1 and MCHR2. The expression of Mchr1 has been investigated in both rats and mice, but its synthesis remains poorly described. After identifying an antibody that detects MCHR1 with high specificity, we employed immunohistochemistry to map the distribution of MCHR1 in the CNS of rats and mice. Multiple neurochemical markers were also employed to characterize some of the neuronal populations that synthesize MCHR1. Our results show that MCHR1 is abundantly found in a subcellular structure called the primary cilium, which has been associated, among other functions, with the detection of free neurochemical messengers present in the extracellular space. Ciliary MCHR1 was found in a wide range of areas, including the olfactory bulb, cortical mantle, striatum, hippocampal formation, amygdala, midline thalamic nuclei, periventricular hypothalamic nuclei, midbrain areas, and in the spinal cord. No differences were observed between male and female mice, and interspecies differences were found in the caudate-putamen nucleus and the subgranular zone. Ciliary MCHR1 was found in close association with several neurochemical markers, including tyrosine hydroxylase, calretinin, kisspeptin, estrogen receptor, oxytocin, vasopressin, and corticotropin-releasing factor. Given the role of neuronal primary cilia in sensing free neurochemical messengers in the extracellular fluid, the widespread distribution of ciliary MCHR1, and the diverse neurochemical populations who synthesize MCHR1, our data indicate that nonsynaptic communication plays a prominent role in the normal function of the MCH system.

The role of co-neurotransmitters in sleep and wake regulation.

Sleep and wakefulness control in the mammalian brain requires the coordination of various discrete interconnected neurons. According to the most conventional sleep model, wake-promoting neurons (WPNs) and sleep-promoting neurons (SPNs) compete for network dominance, creating a systematic "switch" that results in either the sleep or awake state. WPNs and SPNs are ubiquitous in the brainstem and diencephalon, areas that together contain <1% of the neurons in the human brain. Interestingly, many of these WPNs and SPNs co-express and co-release various types of the neurotransmitters that often have opposing modulatory effects on the network. Co-transmission is often beneficial to structures with limited numbers of neurons because it provides increasing computational capability and flexibility. Moreover, co-transmission allows subcortical structures to bi-directionally control postsynaptic neurons, thus helping to orchestrate several complex physiological functions such as sleep. Here, we present an in-depth review of co-transmission in hypothalamic WPNs and SPNs and discuss its functional significance in the sleep-wake network.

Estrogen imprinting compromises male sexual behavior and affects the number of androgen-receptor-expressing hypothalamic neurons†.

Neonatal exposure to high-dose 17ß-estradiol (E2) affects the morphology and physiology of sex and accessory sex organs in the long term. In this study, we examined the effects of E2 imprinting on male sexual behavior, fertility, and the number of androgen receptor (AR)-expressing cells in the hypothalamus. E2-treated males showed copulatory behavior represented by mounts and/or intromissions, demonstrating the preservation of aspects of male behavior. They had slightly increased latency for first intromission and a reduced number of ejaculations, associated with a 50% reduction in the fertility index. AR expression in the hypothalamus was assessed by RT-PCR, western blotting, and immunohistochemistry. Treated rats had a significantly lower ventral prostate (VP) weight, demonstrating the efficacy of the treatment. The AR mRNA and protein content in the hypothalamus of E2-treated animals was reduced to the levels of females. AR-expressing cell counts in the ventromedial, anterior medial preoptic, paraventricular nuclei, and preoptic areas were different from control males, and similar to those of females. In conclusion, E2 imprinting resulted not only in ill-developed sexual organs, but also affected sexual behavior, resulting in a female-type hypothalamus, at least with respect to the abundance of AR mRNA and protein and the number of AR-expressing cells in important regions/tracts.

Dopamine: Functions, Signaling, and Association with Neurological Diseases.

The dopaminergic system plays important roles in neuromodulation, such as motor control, motivation, reward, cognitive function, maternal, and reproductive behaviors. Dopamine is a neurotransmitter, synthesized in both central nervous system and the periphery, that exerts its actions upon binding to G protein-coupled receptors. Dopamine receptors are widely expressed in the body and function in both the peripheral and the central nervous systems. Dopaminergic signaling pathways are crucial to the maintenance of physiological processes and an unbalanced activity may lead to dysfunctions that are related to neurodegenerative diseases. Unveiling the neurobiology and the molecular mechanisms that underlie these illnesses may contribute to the development of new therapies that could promote a better quality of life for patients worldwide. In this review, we summarize the aspects of dopamine as a catecholaminergic neurotransmitter and discuss dopamine signaling pathways elicited through dopamine receptor activation in normal brain function. Furthermore, we describe the potential involvement of these signaling pathways in evoking the onset and progression of some diseases in the nervous system, such as Parkinson's, Schizophrenia, Huntington's, Attention Deficit and Hyperactivity Disorder, and Addiction. A brief description of new dopaminergic drugs recently approved and under development treatments for these ailments is also provided.

Profound degeneration of wake-promoting neurons in Alzheimer's disease.

INTRODUCTION: Sleep-wake disturbances are a common and early feature in Alzheimer's disease (AD). The impact of early tau pathology in wake-promoting neurons (WPNs) remains unclear. METHODS: We performed stereology in postmortem brains from AD individuals and healthy controls to identify quantitative differences in morphological metrics in WPNs. Progressive supranuclear palsy (PSP) and corticobasal degeneration were included as disease-specific controls. RESULTS: The three nuclei studied accumulate considerable amounts of tau inclusions and showed a decrease in neurotransmitter-synthetizing neurons in AD, PSP, and corticobasal degeneration. However, substantial neuronal loss was exclusively found in AD. DISCUSSION: WPNs are extremely vulnerable to AD but not to 4 repeat tauopathies. Considering that WPNs are involved early in AD, such degeneration should be included in the models explaining sleep-wake disturbances in AD and considered when designing a clinical intervention. Sparing of WPNs in PSP, a condition featuring hyperinsomnia, suggest that interventions to suppress the arousal system may benefit patients with PSP.

Behavioral alterations and Fos protein immunoreactivity in brain regions of bile duct-ligated cirrhotic rats.

Hepatic encephalopathy (HE) encompasses a variety of neuropsychiatric symptoms, including anxiety and psychomotor dysfunction. Although HE is a frequent complication of liver cirrhosis, the neurobiological substrates responsible for its clinical manifestations are largely unclear. In the present study, male Wistar rats were bile duct-ligated (BDL), a procedure which induces liver cirrhosis, and on the 21st day after surgery tested in the elevated plus-maze (EPM) and in an open field for anxiety and locomotor activity measurements. Analysis of Fos protein immunoreactivity (Fos-ir) was used to better understand the neurobiological alterations present in BDL animals. Plasma levels of ammonia were quantified and histopathological analysis of the livers was performed. BDL rats showed a significant decrease in the percentage of entries and time spent in the open arms of the EPM, an anxiogenic effect. These animals also presented significant decreases in Fos-ir in the lateral septal nucleus and medial amygdalar nucleus. Their ammonia plasma levels were significantly higher when compared to the sham group and the diagnosis of cirrhosis was confirmed by histopathological analysis. These results indicate that the BDL model induces anxiogenic results, possibly related to changes in the activation of anxiety-mediating circuitries and to increases in ammonia plasma levels.

CRF type 1 receptors of the medial amygdala modulate inhibitory avoidance responses in the elevated T-maze.

Corticotropin-releasing factor (CRF) plays a critical role in the mediation of physiological and behavioral responses to stressors. In the present study, we investigated the role played by the CRF system within the medial amygdala (MeA) in the modulation of anxiety and fear-related responses. Male Wistar rats were bilaterally administered into the MeA with CRF (125 and 250 ng/0.2µl, experiment 1) or with the CRFR1 antagonist antalarmin (25 ng/0.2 µl, experiment 2) and 10 min later tested in the elevated T-maze (ETM) for inhibitory avoidance and escape measurements. In clinical terms, these responses have been respectively related to generalized anxiety and panic disorder. To further verify if the anxiogenic effects of CRF were mediated by CRFR1 activation, we also investigated the effects of the combined treatment with CRF (250 ng/0.2 µl) and antalarmin (25 ng/0.2 µl) (experiment 3). All animals were tested in an open field, immediately after the ETM, for locomotor activity assessment. Results showed that CRF, in the two doses administered, facilitated ETM avoidance, an anxiogenic response. Antalarmin significantly decreased avoidance latencies, an anxiolytic effect, and was able to counteract the anxiogenic effects of CRF. None of the compounds administered altered escape responses or locomotor activity measurements. These results suggest that CRF in the MeA exerts anxiogenic effects by activating type 1 receptors, which might be of relevance to the physiopathology of generalized anxiety disorder.

Navigating the complex terrain of motivated behavior: a bibliometric and neuroscientific perspective.

Over several decades, motivated behavior has emerged as a crucial study area within neuroscience. Understanding the neural substrates and mechanisms driving behaviors related to reward, addiction, and other motivation forms is pivotal for novel therapeutic interventions. This review provides a bibliometric analysis of the literature, highlighting the main trends, influential authors, and the potential future direction of the field. Utilizing a dataset comprised by 3,150 publications from the Web of Science and Scopus databases ("motivated behavior as query), we delve into key metrics like publication trends, keyword prevalence, author collaborations, citation impacts, and employed an unsupervised natural language processing technique - Latent Dirichlet Allocation - for topic modeling. From early investigations focusing on basic neural mechanism and behaviors in animal models to more recent studies exploring the complex interplay of neurobiological, psychological, and social factors in humans, the field had undergone a remarkable transformation. The last century has seen a proliferation of research dedicated to uncovering the intricacies of motivation, significantly enriching our understanding of its myriad implications for human behavior and mental health. This bibliometric analysis aims to offer comprehensive insights into this dynamic research area, highlighting the field's key contributions and potential future directions, thereby serving as a valuable resource for researchers, and hopefully give a more thorough understanding of the research area.

Kinin B1 receptor gene ablation affects hypothalamic CART productionb.

A role for the kinin B1 receptor in energy-homeostatic processes was implicated in previous studies; notably, the studies where kinin B1 receptor knockout mice (B1-/-) were shown to have impaired adiposity, impaired leptin and insulin production, lower feed efficiency, protection from liver steatosis and diet-induced obesity when fed a high fat diet (HFD). In particular, in a model where the B1 receptor is expressed exclusively in the adipose tissue, it rescues the plasma insulin concentration and the weight gain seen in wild type mice. Taking into consideration that leptin participates in the formation of hypothalamic nuclei, which modulate energy expenditure, and feeding behavior, we hypothesized that these brain regions could also be altered in B1-/- mice. We observed for the first time a difference in the gene expression pattern of cocaine and amphetamine related transcript (CART) in the (lateral hypothalamic area (LHA) resulting from the deletion of the kinin B1 receptor gene. The correlation between CART expression in the LHA and the thwarting of diet-induced obesity corroborates independent correlations between CART and obesity. Furthermore, it seems to indicate that the mechanism underlying the 'lean' phenotype of B1-/- mice does not stem solely from changes in peripheral tissues but may also receive contributions from changes in the hypothalamic machinery involved in energy homeostasis processes.

Anatomical organization of the melanin-concentrating hormone peptide family in the mammalian brain.

More than 20 years ago, melanin-concentrating hormone (MCH) and its peptide family members - neuropeptide EI (NEI) and neuropeptide GE (NGE) - were described in various species, including mammals (rodents, humans, and non-human primates). Since then, most studies have focused on the role of MCH as an orexigenic peptide, as well as on its participation in learning, spatial memory, neuroendocrine control, and sleep. It has been shown that MCH mRNA or the neuropeptide MCH are present in neurons of the prosencephalon, hypothalamus and brainstem. However, most of the neurons containing MCH/NEI are within the incerto-hypothalamic and lateral hypothalamic areas. In addition, the terminals of those neurons are distributed widely throughout the central nervous system. In this review, we will discuss the relationship between those territories and the roles played by MCH/NEI, as well as the importance of MCH receptor 1 in the respective terminal fields. Certain neurochemical features of MCH- and NEI-immunoreactive (MCH-ir and NEI-ir) neurons will also be discussed. The overarching theme is the anatomical organization of an inhibitory neuropeptide colocalized with an inhibitory neurotransmitter in integrative territories of the central nervous system, such as the IHy and LHA. Although these territories have connections to few brain regions, the regions to which they are connected are relevant, being responsible for the organization of motivated behaviors. All available information on this peptidergic system (anatomical, neurochemical, hodological, physiological, pharmacological and behavioral data) suggests that MCH is intimately involved in arousal and the initiation of motivated behaviors.

Distribution of growth hormone-responsive cells in the brain of rats and mice.

A growth hormone (GH) injection is able to induce the phosphorylated form of the signal transducer and activator of transcription 5 (pSTAT5) in a large number of cells throughout the mouse brain. The present study had the objective to map the distribution of GH-responsive cells in the brain of rats that received an intracerebroventricular injection of GH and compare it to the pattern found in mice. We observed that rats and mice exhibited a similar distribution of GH-induced pSTAT5 in the majority of areas of the telencephalon, hypothalamus and brainstem. However, rats exhibited a higher density of GH-responsive cells than mice in the horizontal limb of the diagonal band of Broca (HDB), supraoptic and suprachiasmatic nuclei, whereas mice displayed more GH-responsive cells than rats in the hippocampus, lateral hypothalamic area and dorsal motor nucleus of the vagus (DMX). Since both HDB and DMX contain acetylcholine-producing neurons, pSTAT5 was co-localized with choline acetyltransferase in GH-injected animals. We found that 50.0 ± 4.5% of cholinergic neurons in the rat HDB coexpressed GH-induced pSTAT5, whereas very few co-localizations were observed in the mouse HDB. In contrast, rats displayed fewer cholinergic neurons responsive to GH in the DMX at the level of the area postrema. In summary, pSTAT5 can be used as a marker of GH-responsive cells in the rat brain. Although rats and mice exhibit a relatively similar distribution of GH-responsive neurons, some species-specific differences exist, as exemplified for the responsiveness to GH in distinct populations of cholinergic neurons.

Fasting reduces the number of TRH immunoreactive neurons in the hypothalamic paraventricular nucleus of male rats, but not in mice.

During fasting or weight loss, the fall in leptin levels leads to suppression of thyrotropin-releasing hormone (TRH) expression in the paraventricular nucleus of the hypothalamus (PVH) and, consequently, inhibition of the hypothalamic-pituitary-thyroid (HPT) axis. However, differently than rats, just few PVHTRH neurons express the leptin receptor in mice. In the present study, male adult rats and mice were submitted to 48 -h fasting to evaluate the consequences on proTRH peptide expression at the PVH level. Additionally, the proTRH peptide expression was also assessed in the brains of leptin-deficient (Lepob/ob) mice. We observed that approximately 50 % of PVHTRH neurons of leptin-injected rats exhibited phosphorylation of the signal transducer and activator of transcription 3 (pSTAT3), a marker of leptin receptor activation. In contrast, very few PVHTRH neurons of leptin-injected mice exhibited pSTAT3. Rats submitted to 48 -h fasting showed a significant reduction in the number of PVHTRH immunoreactive neurons, as compared to fed rats. On the other hand, no changes in the number of PVHTRH immunoreactive neurons were observed between fasted and fed mice. Next, the number of TRH immunoreactive cells was determined in the PVH, dorsomedial nucleus of the hypothalamus and nucleus raphe pallidus of Lepob/ob and wild-type mice and no significant differences were observed, despite reduced plasma T4 levels in Lepob/ob mice. Taken together, these findings provide additional evidence of the important species-specific differences in the mechanisms used by fasting and/or leptin to regulate the HPT axis.

The ventral premammillary nucleus links fasting-induced changes in leptin levels and coordinated luteinizing hormone secretion.

Physiological conditions of low leptin levels like those observed during negative energy balance are usually characterized by the suppression of luteinizing hormone (LH) secretion and fertility. Leptin administration restores LH levels and reproductive function. Leptin action on LH secretion is thought to be mediated by the brain. However, the neuronal population that mediates this effect is still undefined. The hypothalamic ventral premammillary nucleus (PMV) neurons express a dense concentration of leptin receptors and project to brain areas related to reproductive control. Therefore, we hypothesized that the PMV is well located to mediate leptin action on LH secretion. To test our hypothesis, we performed bilateral excitotoxic lesions of the PMV in adult female rats. PMV-lesioned animals displayed a clear disruption of the estrous cycle, remaining in anestrus for 15-20 d. After apparent recovery of cyclicity, animals perfused in the afternoon of proestrus showed decreased Fos immunoreactivity in the anteroventral periventricular nucleus and in gonadotropin releasing hormone neurons. PMV-lesioned animals also displayed decreased estrogen and LH secretion on proestrus. Lesions caused no changes in mean food intake and body weight up to 7 weeks after surgery. We further tested the ability of leptin to induce LH secretion in PMV-lesioned fasted animals. We found that complete lesions of the PMV precluded leptin stimulation of LH secretion on fasting. Our findings demonstrate that the PMV is a key site linking changing levels of leptin and coordinated control of reproduction.

Differences between rats and mice in the leptin action on the paraventricular nucleus of the hypothalamus: Implications for the regulation of the hypothalamic-pituitary-thyroid axis.

Previous studies indicate that leptin regulates the hypothalamic-pituitary-thyroid (HPT) axis via direct and indirect mechanisms. The indirect mechanism involves leptin action in pro-opiomelanocortin (POMC)- and agouti-related peptide (AgRP)-expressing neurones. These cells innervate the paraventricular nucleus of the hypothalamus (PVH) where they modulate hypophysiotrophic thyrotrophin-releasing hormone (TRH)-producing neurones. The direct mechanism involves the expression of leptin receptor (LepR) in a subpopulation of PVH TRH neurones. However, to our knowledge, the existence of LepR in PVH TRH neurones of mice has not been clearly confirmed. Therefore, we investigated possible species-specific differences between rats and mice with respect to the mechanisms recruited by leptin to regulate the HPT axis. We observed that an acute leptin injection induced phosphorylated signal transducer and activator of transcription 3 (pSTAT3), a marker of leptin-responsive cells, in 46.2 ± 8.0% of PVH proTRH immunoreactive neurones in rats. By contrast, an insignificant number of proTRH positive neurones in the mouse PVH co-expressed leptin-induced pSTAT3 or LepR. Similarly, central leptin injection increased the percentage of PVH proTRH neurones containing cAMP response element-binding protein phosphorylation in rats, but not in mice. We investigated the innervation of AgRP and POMC axons in the PVH and observed that rats exhibited a denser POMC innervation in the PVH compared to mice, whereas rats and mice showed similar density of AgRP axons in the PVH. In conclusion, rats and mice exhibit important species-specific differences in the direct and indirect mechanisms used by leptin to regulate the HPT axis.

Regulation and neurochemical identity of melanin-concentrating hormone neurones in the preoptic area of lactating mice.

Neurones expressing the melanin-concentrating hormone (MCH) can be found in the medial preoptic area (mPOA) and ventral aspects of the periventricular preoptic nucleus of rats by mid-to-late lactation and this expression disappears after weaning. The transitory expression of MCH in the preoptic area suggests a role for these neurones in the control of the end of lactation. However, the neurochemical identity of mPOA MCH neurones and the regulatory factors that control the transient MCH expression remain largely unknown, especially in the mouse. In the present study, we showed that mice also present the transitory expression of MCH in the mPOA at late lactation. mPOA MCH cells did not colocalise significantly with markers of GABAergic (VGAT), glutamatergic (VGLUT2 and VGLUT3) or dopaminergic (tyrosine hydroxylase) neurones. mPOA MCH cells also did not express Kiss1 or oxytocin. By contrast, approximately 70% and 90% of mPOA MCH neurones colocalised with oestrogen receptor α and prolactin-induced phosphorylated signal transducer and activator of transcription 5 (STAT5), respectively. Finally, we demonstrated that the number of MCH neurones in the mPOA is significantly higher in females during the first lactation, compared to mice on the second lactation or pregnant mice during the first lactation or brain-specific STAT5 knockout mice during the first lactation. In summary, our findings indicate that MCH neurones in the mPOA of lactating mice are sensitive to oestrogens and prolactin. Thus, mPOA MCH expression is possibly influenced by hormonal variations. Furthermore, the STAT5 signalling pathway is likely involved in the regulation of MCH expression in the mPOA of lactating mice.

The Rat Mammary Gland as a Novel Site of Expression of Melanin-Concentrating Hormone Receptor 1 mRNA and Its Protein Immunoreactivity.

Lactation is a complex physiological process, depending on orchestrated central and peripheral events, including substantial brain plasticity. Among these events is a novel expression of pro-melanin-concentrating hormone (Pmch) mRNA in the rodent hypothalamus, such as the ventral part of the medial preoptic area (vmMPOA). This expression reaches its highest levels around postpartum day 19 (PPD19), when dams transition from lactation to the weaning period. The appearance of this lactation-related Pmch expression occurs simultaneously with the presence of one of the Pmch products, melanin-concentrating hormone (MCH), in the serum. Given the relevance of the MPOA to maternal physiology and the contemporaneity between Pmch expression in this structure and the weaning period, we hypothesized that MCH has a role in the termination of lactation, acting as a mediator between central and peripheral changes. To test this, we investigated the presence of the MCH receptor 1 (MCHR1) and its gene expression in the mammary gland of female rats in different stages of the reproductive cycle. To that end, in situ hybridization, RT-PCR, RT-qPCR, nucleotide sequencing, immunohistochemistry, and Western blotting were employed. Although Mchr1 expression was detected in the epidermis and dermis of both diestrus and lactating rats, parenchymal expression was exclusively found in the functional mammary gland of lactating rats. The expression of Mchr1 mRNA oscillated through the lactation period and reached its maximum in PPD19 dams. Presence of MCHR1 was confirmed with immunohistochemistry with preferential location of MCHR1 immunoreactive cells in the alveolar secretory cells. As was the case for gene expression, the MCHR1 protein levels were significantly higher in PPD19 than in other groups. Our data demonstrate the presence of an anatomical basis for the participation of MCH peptidergic system on the control of lactation through the mammary gland, suggesting that MCH could modulate a prolactation action in early postpartum days and the opposite role at the end of the lactation.

Forebrain projections to brainstem nuclei involved in the control of mandibular movements in rats.

Mandibular movements occur through the triggering of trigeminal motoneurons. Aberrant movements by orofacial muscles are characteristic of orofacial motor disorders, such as nocturnal bruxism (clenching or grinding of the dentition during sleep). Previous studies have suggested that autonomic changes occur during bruxism episodes. Although it is known that emotional responses increase jaw movement, the brain pathways linking forebrain limbic nuclei and the trigeminal motor nucleus remain unclear. Here we show that neurons in the lateral hypothalamic area, in the central nucleus of the amygdala, and in the parasubthalamic nucleus, project to the trigeminal motor nucleus or to reticular regions around the motor nucleus (Regio h) and in the mesencephalic trigeminal nucleus. We observed orexin co-expression in neurons projecting from the lateral hypothalamic area to the trigeminal motor nucleus. In the central nucleus of the amygdala, neurons projecting to the trigeminal motor nucleus are innervated by corticotrophin-releasing factor immunoreactive fibers. We also observed that the mesencephalic trigeminal nucleus receives dense innervation from orexin and corticotrophin-releasing factor immunoreactive fibers. Therefore, forebrain nuclei related to autonomic control and stress responses might influence the activity of trigeminal motor neurons and consequently play a role in the physiopathology of nocturnal bruxism.

The Melanin-Concentrating Hormone (MCH) System: A Tale of Two Peptides.

The melanin-concentrating hormone (MCH) system is a robust integrator of exogenous and endogenous information, modulating arousal and energy balance in mammals. Its predominant function in teleosts, however, is to concentrate melanin in the scales, contributing to the adaptive color change observed in several teleost species. These contrasting functions resulted from a gene duplication that occurred after the teleost divergence, which resulted in the generation of two MCH-coding genes in this clade, which acquired distinctive sequences, distribution, and functions, examined in detail here. We also describe the distribution of MCH immunoreactivity and gene expression in a large number of species, in an attempt to identify its core elements. While initially originated as a periventricular peptide, with an intimate relationship with the third ventricle, multiple events of lateral migration occurred during evolution, making the ventrolateral and dorsolateral hypothalamus the predominant sites of MCH in teleosts and mammals, respectively. Substantial differences between species can be identified, likely reflecting differences in habitat and behavior. This observation aligns well with the idea that MCH is a major integrator of internal and external information, ensuring an appropriate response to ensure the organism's homeostasis. New studies on the MCH system in species that have not yet been investigated will help us understand more precisely how these habitat changes are connected to the hypothalamic neurochemical circuits, paving the way to new intervention strategies that may be used with pharmacological purposes.

Nomenclature and Comparative Morphology of the Teneurin/TCAP/ADGRL Protein Families.

The teneurins are a family of glycosylated type II transmembrane proteins synthesized in several tissue from both vertebrate and invertebrate species. These proteins interact with the latrophilins, a group of adhesion G protein-coupled receptors. Both teneurins and latrophilins may have been acquired by choanoflagellates through horizontal gene transfer from a toxin-target system present in prokaryotes. Teneurins are highly conserved in eukaryotes, with four paralogs (TEN1, TEN2, TEN3, and TEN4) in most vertebrates playing a role in the normal neural development, axonal guiding, synapse formation and synaptic maintenance. In this review, we summarize the main findings concerning the distribution and morphology of the teneurins and latrophilins, both during development and in adult animals. We also briefly discuss the current knowledge in the distribution of the teneurin C-terminal associated protein (TCAP), a peptidergic sequence at the terminal portion of teneurins that may be independently processed and secreted. Through the analysis of anatomical data, we draw parallels to the evolution of those proteins and the increasing complexity of this system, which mirrors the increase in metazoan sensory complexity. This review underscores the need for further studies investigating the distribution of teneurins and latrophilins and the use of different animal models.