Receptor Mc1r Research Articles

Analysis of the Melanocortin Brain System of a Krushinsky–Molodkina Rats with Genetic Predisposition to Audiogenic Seizures

The study was conducted on 4-month-old male rats of the Krushinsky–Molodkina (KM) line, genetically predisposed to audiogenic seizures, and Wistar rats, which are not sensitive to the effects of sound. In KM rats, real-time PCR revealed an increase in the level of AgRP mRNA (4-fold, p0.05) and melanocortin receptors MC4R (2.4-fold, p0.05) in the hypothalamus vs. Wistar rats. No differences in the level of proopiomelanocortin mRNA were detected. The results of immunohistochemical analysis indicate an increased (p0.05) level of optical density of AgRP, MC3R and MC4R in the hypothalamic structures of KM rats vs. Wistar rats. In the dorsal hippocampus a statistically significant increase in the level of MC3R (by Western blotting) and MC4R (by immunohistochemistry) was also detected in KM rats vs. Wistar rats. The obtained results are discussed in connection with the revealed blocking dose-dependent effect of SHU9119, a non-selective MC3R/MC4R inhibitor, on seizure activity in KM rats.

Molecular and genetic characterization of sex-linked orange coat color in the domestic cat.

The Sex-linked orange mutation in domestic cats causes variegated patches of reddish/yellow hair and is a defining signature of random X-inactivation in female tortoiseshell and calico cats. Unlike the situation for most coat color genes, there is no apparent homolog for Sex-linked orange in other mammals. We show that the Sex-linked orange is caused by a 5 kb deletion that leads to ectopic and melanocyte-specific expression of the Rho GTPase Activating Protein 36 ( Arhgap36 ) gene. Single cell RNA-seq studies from fetal cat skin reveal that red/yellow hair color is caused by reduced expression of melanogenic genes that are normally activated by the Melanocortin 1 receptor (Mc1r)-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway, but the Mc1r gene and its ability to stimulate cAMP accumulation is intact. Instead, we show that increased expression of Arhgap36 in melanocytes leads to reduced levels of the PKA catalytic subunit (PKA C ); thus, Sex-linked orange is genetically and biochemically downstream of Mc1r . Our findings solve a comparative genomic conundrum, provide in vivo evidence for the ability of Arhgap36 to inhibit PKA, and reveal a molecular explanation for a charismatic color pattern with a rich genetic history.

Effects of Water Temperature on the Body Color and Expression of the Genes Related to Body Color Regulation in the Goldfish.

Melanin-concentrating hormone (MCH), melanocyte-stimulating hormone (MSH), and somatolactin (SL) in the hypothalamus-pituitary axis are associated with body color regulation in teleost fish. Although these hormones' production and secretion respond well to light environments, such as background color, little is known about the effects of different water temperatures. We investigated the effects of water temperature, 10°C, 20°C, and 30°C, on body color and the expression of these genes and corresponding receptor genes in goldfish. The body color in white background (WBG) becomes paler at the higher water temperature, although no difference was observed in black background (BBG). Brain mRNA contents of proMCH genes (pmch1 and pmch2) increased at 30°C and 20°C compared to 10°C in WBG, respectively. Apparent effects of background color and temperature on the pituitary mRNA contents of a POMC gene (pomc) were not observed. The pituitary mRNA contents of the SLα gene were almost double those on a WBG at any temperature, while those of the SLβ gene (slb) at 30°C tended to be higher than those at 10°C and 20°C on WBG and BBG. The scale mRNA contents of the MCH receptor gene (mchr2) in WBG were higher than those in BBG at 30°C. The highest scale mRNA contents of MSH receptor (mc1r and mc5r) on BBG were observed at 20°C, while the lowest respective mRNA levels were observed at 30°C on WBG. These results highlight the importance of temperature for the endocrinological regulation of body color, and darker background color may stabilize those endocrine functions.

Evaluation of Ex Vivo Adrenocorticotropic Hormone Responsiveness of Human Fetal Testis.

Testicular adrenal rest tumors (TARTs), commonly occurring in males with congenital adrenal hyperplasia, may arise from chronic stimulation of adrenocorticotropic hormone (ACTH)-sensitive cells in the testes. It is not yet established whether the human fetal testis (HFT) is responsive to ACTH. To investigate this, we cultured HFT tissue with and without ACTH for up to 5 days, and quantified adrenal steroid hormones and expression of adrenal steroidogenic enzymes. Fetal testis and adrenal tissue produced high levels of testosterone and cortisol, respectively, indicating viability. In contrast to fetal adrenal tissues, the expression of ACTH receptor MC2R was either absent or expressed at extremely low levels in ex vivo HFT tissue and no clear response to ACTH in gene expression or steroid hormone production was observed. Altogether, this study suggests that the HFT is unresponsive to ACTH, which would indicate that a TART does not arise from fetal testicular cells chronically exposed to ACTH in utero.

Genetic architectures of postmating isolation and morphology of two highly diverged rockfishes (genus Sebastes).

Postmating isolation is thought to be an important driver of the late stages of speciation. However, relatively little is empirically known about the process compared with other isolating mechanisms that drive the early stages of speciation, especially in non-model organisms. We characterized the genetic architecture of postmating isolation between 2 rockfishes, Sebastes schlegelii and S. trivittatus, whose reproductive isolation is complete. We examined transmission ratio distortion (TRD) patterns of genetic markers in 2 reciprocal backcross populations. Markers showing either of the 2 types of TRD was widespread across the genome, with some of the distorted markers forming extensive clusters around the recombination coldspots. These suggest that the postmating isolation effectively prevents gene flow across the genome and the recombination landscape contributes to the genetic architecture. Comparisons between 2 backcross families and 2 developmental stages showed little similarity in the distorted markers, suggesting asymmetry and stage specificity of the isolation. This may be due to hybrid incompatibility involving maternal factors or extrinsic selection. The lack of sex-ratio distortion in the mapping families suggested that Haldane's rule in terms of hybrid inviability does not hold. Additionally, quantitative trait loci (QTL) mapping detected significant QTLs for sex and the morphological traits relevant to speciation and convergence of rockfishes, including body coloration. Genes in the melanocortin system, including agouti-signaling protein 1 (asip1) and melanocortin 1 receptor (mc1r), might underlie the horizontal and vertical color patterns on the body, respectively. These findings constitute an essential step toward a comprehensive understanding of speciation and morphological diversification of rockfishes.

Effect of the renin-angiotensin system on the exacerbation of adrenal glucocorticoid steroidogenesis in diabetic mice: Role of angiotensin-II type 2 receptor.

Prior investigation shows an increase in the activity of both hypothalamus-pituitary-adrenal (HPA) axis and the renin-angiotensin system (RAS) in diabetic patients. Moreover, activation of angiotensin-II type 1 receptor (AT1) has been associated with adrenal steroidogenesis. This study investigates the role of RAS on the overproduction of corticosterone in diabetic mice. Diabetes was induced by intravenous injection of alloxan into fasted Swiss-webster mice. Captopril (angiotensin-converting enzyme inhibitor), Olmesartan (AT1 receptor antagonist), CGP42112A (AT2 receptor agonist) or PD123319 (AT2 receptor antagonist) were administered daily for 14 consecutive days, starting 7 days post-alloxan. Plasma corticosterone was evaluated by ELISA, while adrenal gland expressions of AT1 receptor, AT2 receptor, adrenocorticotropic hormone receptor MC2R, pro-steroidogenic enzymes steroidogenic acute regulatory protein (StAR), and 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) were assessed using immunohistochemistry or western blot. Diabetic mice showed adrenal gland overexpression of AT1 receptor, MC2R, StAR, and 11βHSD1 without altering AT2 receptor levels, all of which were sensitive to Captopril or Olmesartan treatment. In addition, PD123319 blocked the ability of Olmesartan to reduce plasma corticosterone levels in diabetic mice. Furthermore, CGP42112A significantly decreased circulating corticosterone levels in diabetic mice, without altering the overexpression of MC2R and StAR in the adrenal glands. Our findings revealed that inhibition of both angiotensin synthesis and AT1 receptor activity reduced the high production of corticosterone in diabetic mice via the reduction of MC2R signaling expression in the adrenal gland. Furthermore, the protective effect of Olmesartan on the overproduction of corticosterone by adrenals in diabetic mice depends on both AT1 receptor blockade and AT2 receptor activation.

Enhanced Anti-Melanogenic Effect of Adlay Bran Fermented with Lactobacillus brevis MJM60390

Fermentation is a traditional technique used to increase nutrients, flavonoids, vitamins, minerals, and the flavor of raw materials. In this study, adlay bran was fermented by Lactobacillus brevis MJM60390 (FAB), and the anti-melanogenic effect was investigated. The results demonstrated that FAB significantly suppressed melanin accumulation in mouse melanogenic B16F10 cells, and the activity was higher than non-fermented adlay bran (NFAB). The molecular mechanism study showed that FAB inhibited melanin synthesis by suppressing the gene expression of melanocortin 1 receptor (Mc1r), melanocyte-inducing transcription factor (Mitf), tyrosinase (Tyr), tyrosinase-related protein-1 (Trp-1), and tyrosinase-related protein-2 (Trp-2) genes. Western blotting analysis showed that FAB strongly decreased the expression of Tyr, Trp-1, and Trp-2 compared to NFAB. Furthermore, phenolic compounds such as gallic acid, p-coumaric acid, ferulic acid, and sinapic acid, which are known for their anti-melanogenic effects, were significantly increased in FAB compared with NFAB. These findings suggest that FAB holds great potential as an anti-melanogenic agent and can be used for the development of whitening cosmetics.

Natural Killer cells demonstrate distinct eQTL and transcriptome-wide disease associations, highlighting their role in autoimmunity

Natural Killer cells are innate lymphocytes with central roles in immunosurveillance and are implicated in autoimmune pathogenesis. The degree to which regulatory variants affect Natural Killer cell gene expression is poorly understood. Here we perform expression quantitative trait locus mapping of negatively selected Natural Killer cells from a population of healthy Europeans (n = 245). We find a significant subset of genes demonstrate expression quantitative trait loci specific to Natural Killer cells and these are highly informative of human disease, in particular autoimmunity. A Natural Killer cell transcriptome-wide association study across five common autoimmune diseases identifies further novel associations at 27 genes. In addition to these cis observations, we find novel master-regulatory regions impacting expression of trans gene networks at regions including 19q13.4, the Killer cell Immunoglobulin-like Receptor region, GNLY, MC1R and UVSSA. Our findings provide new insights into the unique biology of Natural Killer cells, demonstrating markedly different expression quantitative trait loci from other immune cells, with implications for disease mechanisms.

Role of the Melanocortin System in the Central Regulation of Cardiovascular Functions.

Increasing evidence indicates that the melanocortin system is not only a central player in energy homeostasis, food intake and glucose level regulation, but also in the modulation of cardiovascular functions, such as blood pressure and heart rate. The melanocortins, and in particular α- and γ-MSH, have been shown to exert their cardiovascular activity both at the central nervous system level and in the periphery (e.g., in the adrenal gland), binding their receptors MC3R and MC4R and influencing the activity of the sympathetic nervous system. In addition, some studies have shown that the activation of MC3R and MC4R by their endogenous ligands is able to improve the outcome of cardiovascular diseases, such as myocardial and cerebral ischemia. In this brief review, we will discuss the current knowledge of how the melanocortin system influences essential cardiovascular functions, such as blood pressure and heart rate, and its protective role in ischemic events, with a particular focus on the central regulation of such mechanisms.

Enhanced growth without accelerated puberty in fish: A role for the melanocortin system

In two swordtail species of the genus Xiphophorus, onset of puberty in males and females, fecundity in females, and adult size in males are modulated by sequence polymorphism and gene copy-number variation at the P locus affecting the type 4 melanocortin hormone receptor (Mc4r). The involvement of Mc4r in regulating the onset of puberty outside the genus Xiphophorus remains unclear. In this study we used a transgenic line overexpressing asip1 (asip1-Tg), an endogenous antagonist of both type 1 melanocortin hormone receptor (Mc1r) and Mc4r, to investigate the relevance of the melanocortin system on the onset of puberty and adult reproductive performance in zebrafish (Danio rerio). Comparison of growth, puberty and reproductive performance between wild-type (WT) and asip1-Tg zebrafish revealed that a decreased activity of the melanocortin system did not change the timing of puberty but significantly delayed early growth of transgenic animals. Hatching time was postponed in asip1-Tg fish and they were significantly smaller than their WT siblings at 75 dpf, despite showing enhanced linear growth after having completed puberty. asip1-Tg females produced 1.38 times more eggs but spawned less frequently, and their eggs had showed a 0.89-fold smaller diameter but a 1.04-fold increase in larvae body length at hatching. Therefore, we demonstrate that asip-tg zebrafish do not reach puberty earlier than WT counterparts as it could be expected considering the enhanced length and weight growth during early adulthood. This is so because the effects of transgene on growth are noticeable after a threshold length, when puberty has already been reached. Data show that the inhibition of melanocortin system via asip overexpression is an excellent strategy to promote growth, in absence of obesity, by enhancing food efficiency but without accelerating puberty timing. Data here presented provides a deeper characterization of the phenotype induced by the decreased activity of the melanocortin system in fish thus providing an excellent strategy for future aquaculture especially because U.S. Food and Drug Association has recently approved transgenic fish trading.

Activation of the Melanocortin-1 Receptor by NDP-MSH Attenuates Oxidative Stress and Neuronal Apoptosis through PI3K/Akt/Nrf2 Pathway after Intracerebral Hemorrhage in Mice.

Oxidative stress and neuronal apoptosis play crucial roles in secondary brain injury (SBI) after intracerebral hemorrhage (ICH). Recently, Nle4-D-Phe7-α-melanocyte-stimulating hormone (NDP-MSH), a synthetic agonist of the melanocortin-1 receptor (Mc1r), has been proved to inhibit neuroinflammatory in several diseases. This study is aimed at exploring if NDP-MSH could reduce oxidative stress and neuronal apoptosis following ICH, as well as the potential mechanism. A mouse ICH model was induced by autologous blood injection. NDP-MSH was intraperitoneally injected at 1 h after ICH. Mc1r siRNA and PI3K inhibitor LY294002 were administrated to inhibit the expression of Mc1r and phosphorylation of PI3K, respectively. Neurological test, brain water content, enzyme-linked immunosorbent assay (ELISA), terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), immunofluorescence, and Western blot analysis were utilized in this study. The results exhibited that Mc1r was mainly expressed in neurons, and its level in the ipsilateral hemisphere was significantly elevated after ICH. NDP-MSH treatment significantly attenuated the neurological deficits and brain water content 24 hours after ICH, which was accompanied by the inhibition of oxidative stress and neuronal apoptosis. The administration of NDP-MSH after ICH significantly promoted the expression of Mc1r, p-PI3K, p-Akt, and p-Nrf2, followed by an increase of Bcl-2 and reduction of cleaved caspase-3. Conversely, downregulating the expression of Mc1r and phosphorylation of PI3K aggravated the neurological deficits and brain edema at 24 hours after ICH, meanwhile, the effect of NDP-MSH on the expression of Mc1r, p-PI3K, p-Akt, p-Nrf2, Bcl-2, and cleaved caspase 3 was also abolished. In conclusion, our data suggest that the activation of Mc1r by NDP-MSH ameliorates oxidative stress and neuronal apoptosis through the PI3K/Akt/Nrf2 signaling pathway after ICH in mice.

Sex-dependent alterations of dopamine receptor and glucose transporter density in rat hypothalamus under long-term clozapine and haloperidol medication.

ObjectiveSex‐dependent disturbances of peripheral glucose metabolism are known complications of antipsychotic drug treatment. The influence of long‐term clozapine and haloperidol medication on hypothalamus, maintaining aspects of internal body homeostasis, has not yet been completely clarified.MethodsAfter puberty, male and female Sprague Dawley rats were fed orally with ground pellets containing haloperidol (1 mg/kgBW/day) or clozapine (20 mg/kgBW/day) for 12 weeks. The hypothalamic protein expression of dopamine receptors D2R and D4R, melanocortin receptor MC4R, and glucose transporters Glut1 and Glut3 was examined. Glucose, glycogen, lactate, and pyruvate levels were determined, also malondialdehyde equivalents as markers of oxidative stress.ResultsD2R expression was increased in the male haloperidol and clozapine group but decreased in females medicated with clozapine. D4R expression was upregulated under clozapine medication. While females showed increased Glut1, Glut3 was elevated in both male and female clozapine‐medicated animals. We found no changes of hypothalamic malondialdehyde, glycogen, and MC4R. Hypothalamic lactate was elevated in the female clozapine group.ConclusionClozapine sex‐dependently affects the expression of D2R, Glut1, and Glut3. The upregulation of the glucose transporters indicates glucose deprivation in the endothelial cells and consequently in astrocytes and neurons. Increased hypothalamic lactate in females under clozapine points to enhanced glycolysis with a higher glucose demand to produce the required energy. Haloperidol did not change the expression of the glucose transporters and upregulated D2R only in males.

Species and genetic diversity of Bandicota (Murinae, Rodentia) from Myanmar based on mitochondrial and nuclear gene sequences

Bandicoot rats (genus Bandicota), widely known as rodent pests, are abundant and widespread throughout the continental part of the Indo-Malayan realm. However, their evolutionary history is not yet well understood. The molecular phylogenetic relationships of the three bandicoot rat species, Bandicota bengalensis, Bandicota indica, and Bandicota savilei, were assessed based on the gene sequences of the specimens collected from Myanmar, where all three species occur along with database sequences. Early divergence of B. savilei (1.5–1.7 million years ago) was inferred from the mitochondrial cytochrome b (Cytb) gene and the nuclear interphotoreceptor retinoid-binding protein (Irbp), and melanocortin 1 receptor (Mc1r) gene sequences. The Cytb lineage of B. bengalensis from Sri Lanka was distinct from the monophyletic lineage of the continental lineages of B. bengalensis and B. indica. This can be explained by the preservation of ancient mitochondrial DNA (mtDNA) in the insular population owing to female philopatry and male dispersal, given that no substantial intraspecies geographic subdivision was observed in the nuclear markers. The paraphyletic relationship of B. bengalensis with B. indica may be explained by introgression of the mtDNA from B. bengalensis to B. indica, but further investigation is required to confirm this. B. bengalensis Cytb sequences from a wide area of Myanmar had limited nucleotide diversity (π = 0.00079), implying that the genetic diversity of B. bengalensis in Myanmar was acquired through Holocene human activities.

Local secretion of stress hormones increases in alopecia areata lesions after treatment with UVA-1 phototherapy.

Alopecia areata (AA) is an autoimmune disease of the hair follicle. Keratinocytes of the hair follicle generate an immunosuppressive environment by the local secretion of hormones of the hypothalamic-pituitary-adrenal axis of the skin (skin HPA analog). Our objective was to measure the local production of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and α-melanocyte-stimulating hormone (α-MSH) in the scalp tissue of patients with AA before and after ultraviolet A1 (UVA-1) phototherapy to determine their role in the pathogenesis of AA and the effect of UVA-1 on the AA hormonal environment. This was a retrospective and descriptive study of skin samples from 22 patients with AA before and after UVA-1 treatment. We compared the changes in the local hormonal environment by measuring CRH, ACTH, type 2 melanocortin receptor (ACTH receptor) and α-MSH with immunohistochemical stains. The positivity of MSH was significantly higher (P=.037) in the post-treatment samples compared with the baseline value. ACTH was significantly higher in intensity (P=.032) in the post-treatment samples compared with the initial value. CRH was significantly higher in intensity (P=.013) in baseline samples compared with the final biopsies. The positivity of the ACTH receptor MC2R was not different between the two groups (P=.626). In AA, an interruption in the signalling of CRH could decrease the local concentration of ACTH and MSH, and consequently, the immunosuppressive effect of these hormones. This phenomenon is normalized in the skin treated with UVA-1. A defective signalling system in the cutaneous HPA axis may be involved in the pathogenesis of AA.

MicroRNA-206 Regulation of Skin Pigmentation in Koi Carp (Cyprinus carpio L.).

MicroRNAs (miRNAs) are ∼22 nucleotide non-coding RNA molecules that act as crucial roles in plenty of biological processes. However, the molecular and cellular mechanisms of miRNAs to regulate skin color differentiation and pigmentation in fish have not been fully understood. Herein, we revealed that miR-206, a skin-enriched miRNA, regulates melanocortin 1 receptor (Mc1r, a key regulator of melanogenesis) expression by binding to its 3'-untranslated (UTR) region through bioinformatics and luciferase reporter assay in koi carp (Cyprinus carpio L.). The analysis of spatial and temporal expression patterns suggested that miR-206 is a potential regulator in the skin pigmentation process. Then, we silenced it in vivo with an antagomir method. The result showed a substantial increase of Mc1r mRNA expression and protein level, and also its downstream genes: tyrosinase (Tyr) and dopachrome tautomerase (Dct) that encoding key enzymes involved in melanin synthesis. Moreover, we constructed the miRNA-206 sponge lentivirus vector to transfect koi carp melanocytes in vitro, further checked the functions of melanocytes using Cck-8 and Transwell assays. As a result, inhibition of miR-206 significantly up-regulated Mc1r mRNA expression and protein level and accelerated the melanocyte proliferation and migration ability compared with the scrambled-sequence negative control group (miR-NC). Overall, these findings provide the evidence that miR-206 plays a regulatory role in the skin color pigmentation through targeting the Mc1r gene and would facilitate understanding the molecular regulatory mechanisms underlying miRNA-mediated skin color pigmentation in koi carp.

Effects of background adaptation on the skin color of Malaysian red tilapia

The effects of changes in background color, between white and black, on the apparent body color, the skin L*, a* and b* values, the MSH levels in the serum and the melanin-concentrating hormone (mch), proopiomelanocortin (pomc), melanocortin 1 receptor (mc1r) and tyrosinase (tyr) gene mRNA expressions of Malaysia red tilapia were investigated. After rearing in black (B) or white (W) background tanks for 27 days, the rest fishes were transferred to the same (WW and BB) or opposite (WB and BW) background tanks for another 27 days. The apparent body color of fish was paler in white background and darker in black background, and the body color was reversibly variable in response to transfer to the opposite background color. Correspondingly, the L* and b* values were higher and a* values were lower in white background groups than that in black background groups in the skin of fish (P < .05). The expression of mch gene mRNA in the brain were higher in W fish than in B fish (P < .05). In contrast, the pomc mRNA levels were higher in B group than that in W group in the pituitary of fish (P < .05). However, the MSH levels in the serum of fish were not significantly different between W and B group (P > .05) and peaked in WW group (P < .05). Interestingly, the expressions of pomc in pituitary, mc1r and tyr in dorsal skin of fish on day 27 were higher than that on day 54 (P < .05). The mc1r mRNA expressions in the skin of W and B fish were not significantly different (P > .05). However, BB fish showed significantly higher skin mc1r mRNA expressions than WW and BW fish (P < .05). The tyr mRNA in the ventral skin of red tilapia was highest in B group. And the expression of tyr mRNA in BB group was higher than that in BW, WW and WB groups in the skin of fish (P < .05). Present results will facilitate understanding the mechanism of fish skin color determination.

NDP-MSH binding melanocortin-1 receptor ameliorates neuroinflammation and BBB disruption through CREB/Nr4a1/NF-\u03baB pathway after intracerebral hemorrhage in mice

BackgroundNeuroinflammation and blood-brain barrier (BBB) disruption are two vital mechanisms of secondary brain injury following intracerebral hemorrhage (ICH). Recently, melanocortin-1 receptor (Mc1r) activation by Nle4-D-Phe7-α-MSH (NDP-MSH) was shown to play a neuroprotective role in an experimental autoimmune encephalomyelitis (EAE) mouse model. This study aimed to investigate whether NDP-MSH could alleviate neuroinflammation and BBB disruption after experimental ICH, as well as the potential mechanisms of its neuroprotective roles.MethodsTwo hundred and eighteen male C57BL/6 mice were subjected to autologous blood-injection ICH model. NDP-MSH, an agonist of Mc1r, was administered intraperitoneally injected at 1 h after ICH insult. To further explore the related protective mechanisms, Mc1r small interfering RNA (Mc1r siRNA) and nuclear receptor subfamily 4 group A member 1 (Nr4a1) siRNA were administered via intracerebroventricular (i.c.v) injection before ICH induction. Neurological test, BBB permeability, brain water content, immunofluorescence staining, and Western blot analysis were implemented.ResultsThe Expression of Mc1r was significantly increased after ICH. Mc1r was mainly expressed in microglia, astrocytes, and endothelial cells following ICH. Treatment with NDP-MSH remarkably improved neurological function and reduced BBB disruption, brain water content, and the number of microglia in the peri-hematoma tissue after ICH. Meanwhile, the administration of NDP-MSH significantly reduced the expression of p-NF-κB p65, IL-1β, TNF-α, and MMP-9 and increased the expression of p-CREB, Nr4a1, ZO-1, occludin, and Lama5. Inversely, the knockdown of Mc1r or Nr4a1 abolished the neuroprotective effects of NDP-MSH.ConclusionsTaken together, NDP-MSH binding Mc1r attenuated neuroinflammation and BBB disruption and improved neurological deficits, at least in part through CREB/Nr4a1/NF-κB pathway after ICH.

Mc1r genotype and plumage colouration in highly polymorphic jackal buzzards, Buteo rufofuscus

Evolution is driven by natural selection acting on variable phenotypic traits. Understanding the molecular basis of those traits is crucial for elucidating the mechanisms of natural selection. The southern African jackal buzzard (Buteo rufofuscus) displays extreme plumage colour polymorphism, with colouration on the chest varying from dark black to pale white. In a number of birds and other vertebrates, genetic variation at the melanocortin-1 receptor (Mc1r) gene is associated with melanin-based colour variation. Here, the Mc1r gene was sequenced from 12 jackal buzzard individuals displaying three distinct colour morphs (dark, intermediate and pale). A single nucleotide change was found, which although it resulted in an amino acid change, was shared by all jackal buzzards irrespective of colour morph. Although the Mc1r has played an important role in colour polymorphism in other species, in this study no association between Mc1r genotype and plumage polymorphism in jackal buzzards was found.

Molecular Characterization of Species of the Subgenus Mus from Myanmar.

The species composition and genetic diversity of the subgenus Mus in Myanmar are not yet fully understood. In this study, mice were trapped in rural areas near the Ayeyarwady River basin, spanning five Myanmar cities from north to south: Mandalay, Bagan, Magway, Pyay, and Yangon. Mitochondrial cytochrome b (Cytb) and nuclear melanocortin 1 receptor (Mc1r) gene sequences were determined for mice sampled and revealed a widespread occurrence of Mus nitidulus in central Myanmar in addition to its previously known occurrence in the Yangon district of southern Myanmar. Analyses of Cytb revealed two haplogroups with a genetic distance of 2.0%, suggestive of divergence several hundred thousand years ago. Mus caroli and M. musculus were confined to Yangon and Mandalay/Bagan/Magway, respectively. Mice collected from a locality on the eastern side of the Ayeyarwady River in Pyay were identified using Cytb and Mc1r sequences as M. fragilicauda, which was previously identified only in Laos and Thailand. The species M. booduga and M. cervicolor previously predicted to be common in the study area were not found. These findings elucidate the species and genetic diversity of the subgenus Mus in the Indo-Malayan Region.

Leathesia difformis Extract Inhibits α-MSH-Induced Melanogenesis in B16F10 Cells via Down-Regulation of CREB Signaling Pathway.

Leathesia difformis (L.) Areschoug (L. difformis) is a species of littoral brown algae of the class Phaeophyceae. Only a few studies on the apoptotic, antiviral, and antioxidant properties of L. difformis have been reported, and its inhibitory effect on melanin synthesis has not been studied. The aim of this study was to investigate the anti-melanogenic effect of L. difformis extract on α-melanocyte-stimulating hormone (α-MSH)-induced B16F10 melanocytes and its mechanism of action. L. difformis was extracted using 80% ethanol (LDE) and then fractioned between ethyl acetate (LDE-EA) and water (LDE-A). Our data demonstrated that LDE-EA significantly inhibited melanin level and cellular tyrosinase activity in α-MSH-stimulated B16 cells. In addition, the expression of genes associated with melanin synthesis, such as microphthalmia-associated transcription factor (Mitf), tyrosinase (Tyr), tyrosinase-related protein-1 (Trp-1), dopachrome tautomerase (Dct), and melanocortin 1 receptor (Mc1r) was down-regulated by LDE-EA treatment. Moreover, LDE-EA decreased p-CREB levels, which suggests that the inhibition of the cAMP/PKA/CREB pathways may be involved in the anti-melanogenic effect of LDE-EA. Thus, this study revealed that LDE-EA is an effective inhibitor of hyperpigmentation through inhibition of CREB pathways and may be considered as a potential therapeutic agent for hyperpigmentation disorders.