Neuropeptide Network of Polycystic Ovary Syndrome - A Review.

BACKGROUND: Polycystic Ovary Syndrome (PCOS), the ubiquitous reproductive disorder, has been documented as highly prevalent (6-9%) in India. 10% of women globally are predicted to have the disease. The highly mutable endocrinopathy, with differential clinical criteria for each diagnosis of PCOS, can mask the severity of the syndrome by influencing the incidence and occurrence of PCOS. AREA COVERED: When there is a solid theoretical hypothesis between the neuroendocrine origin and ovarian origin of PCOS, recent evidence supports the neuroendocrine derivation of the pathology. It is considered of neuroendocrine basis - as it controls the ovarian axis and acts as a delicate target because it possesses receptors for various gonadal hormones, neurotransmitters & neuropeptides. Can these neuroendocrine alterations, variations in central brain circuits, and neuropeptide dysregulation be the tie that would link the pathophysiology of the disorder, the occurrence of all the 1˚ and 2˚ symptoms like polycystic ovaries, hyperandrogenism, obesity, insulin resistance, etc., in PCOS? CONCLUSION: This review anticipates providing a comprehensive overview of how neuropeptides such as Kisspeptin, Neurokinin B, Dynorphin A, ß-Endorphin, Nesfatin, Neuropeptide Y, Phoenixin, Leptin, Ghrelin, Orexin, and Neudesin influence PCOS, the understanding of which may help to establish potential drug candidates against precise targets in these central circuits.

The adipose tissue melanocortin 3 receptor is targeted by ghrelin and leptin and may be a therapeutic target in obesity.

OBJECTIVE: Obesity is linked to perturbations in energy balance mechanisms, including ghrelin and leptin actions at the hypothalamic circuitry of neuropeptide Y (NPY) and melanocortin. However, information about the regulation of this system in the periphery is still scarce. Our objective was to study the regulation of the NPY/melanocortin system in the adipose tissue (AT) and evaluate its therapeutic potential for obesity and type 2 diabetes. METHODS: The expression of the NPY/melanocortin receptors' levels was assessed in the visceral AT of individuals with obesity and altered metabolism. Protein levels of these receptors were evaluated in cultured adipocytes incubated with ghrelin (30 and 100 ng/mL) and leptin (1 and 10 nM) and in the AT of an animal model with a mutation in the leptin receptor (ZSF1 rat), to understand their regulation by leptin and ghrelin. The vertical sleeve gastrectomy animal model was used to evaluate the putative therapeutic potential of the NPY/melanocortin system. RESULTS: In this study, we unravelled that leptin (1 nM and 10 nM) selectively reduced the levels of NPY5R and MC3R but no other NPYR/MCRs in cultured adipocytes. In turn, acylated ghrelin (100 ng/mL) significantly increased NPY1R, but the inhibition of its receptor also abrogates MC3R levels. However, in the Lepr-deficient ZSF1 rat, both NPY5R and MC3R levels were reduced, along with other NPYRs and MCRs, suggesting that leptin resistance negatively affects NPY and melanocortin signalling. In human adipose tissue, we found a downregulation of genes encoding the NPY and melanocortin receptors in the visceral AT of individuals with obesity and insulin resistance, being correlated with genes regulating metabolic activity. Additionally, diabetic obese rats submitted to vertical sleeve gastrectomy showed increased levels of NPY, melanocortin, ghrelin, and leptin receptors in the AT, including MC3R, suggesting it may constitute a therapeutic target in obesity. CONCLUSIONS: Our results suggest that the AT NPY/melanocortin system, particularly the MC3R, may be involved in the neuroendocrine regulation of adipocyte metabolism. Altogether, our work shows MC3R is under the control of the ghrelin/leptin duo, is reduced in patients with obesity and prediabetes, and may constitute a therapeutic target in obesity.

Intrathecal administration of MCRT produced potent antinociception in chronic inflammatory pain models via µ-δ heterodimer with limited side effects.

An important goal in the opioid field is to discover effective analgesic drugs with minimal side effects. MCRT demonstrated potent antinociceptive effects with limited side effects, making it a promising candidate. However, its pharmacological properties and how it minimizes side effects remain unknown. Various mouse pain and opioid side effect models were used to evaluate the antinociceptive properties and safety at the spinal level. The targets of MCRT were identified through cAMP measurement, isolated tissue assays, and pharmacological experiments. Immunofluorescence was employed to visualize protein expression. MCRT displayed distinct antinociceptive effects between acute and chronic inflammatory pain models due to its multifunctional properties at the µ opioid receptor (MOR), µ-δ heterodimer (MDOR), and neuropeptide FF receptor 2 (NPFFR2). Activation of NPFFR2 reduced MOR-mediated antinociception, leading to bell-shaped response curves in acute pain models. However, activation of MDOR produced more effective antinociception in chronic inflammatory pain models. MCRT showed limited tolerance and opioid-induced hyperalgesia in both acute and chronic pain models and did not develop cross-tolerance to morphine. Additionally, MCRT did not exhibit addictive properties, gastrointestinal inhibition, and effects on motor coordination. Mechanistically, peripheral chronic inflammation or repeated administration of morphine and MCRT induced an increase in MDOR in the spinal cord. Chronic administration of MCRT had no apparent effect on microglial activation in the spinal cord. These findings suggest that MCRT is a versatile compound that provides potent antinociception with minimal opioid-related side effects. MDOR could be a promising target for managing chronic inflammatory pain and addressing the opioid crisis.

Effects of dietary indispensable amino acid deficiencies on feed intake in stomachless fish.

Evidence suggests that fish are more tolerant than mammals to imbalanced dietary amino acid profiles. However, the behavioral and physiological responses of fish to individual deficiencies in dietary indispensable amino acids (IDAA) remain unclear. This study examined how stomachless fish respond to diets deficient in limiting IDAA (lysine, methionine, and threonine), using Zebrafish (Danio rerio) as a model. The response to deficient diets was assessed based on; 1) growth performance and feeding efficiency; 2) feed intake; 3) expression of appetite-regulating hormones and nutrient-sensing receptors; and 4) muscle postprandial free amino acid (FAA) levels. There were 6 treatments, each with 3 replicate tanks. A semi-purified diet was formulated for each group. The CG diet was based on casein and gelatin, while the FAA50 diet had 50 % of dietary protein supplied with crystalline amino acids. Both were formulated to contain matching, balanced amino acid profiles. The remaining diets were formulated the same as the FAA50 diet, with minor adjustments to create deficiencies in selected IDAA. The (-) Lys, (-) Met, and (-) Thr diets had lysine, methionine, and threonine withheld from the FAA mix, respectively, and the Def diet was deficient in all three. The juvenile Zebrafish were fed to satiation 3 times daily from 21 to 50 days-post-hatch. Results showed that 50 % replacement of dietary protein with crystalline amino acids significantly reduced growth of juvenile Zebrafish. There were no significant differences in growth between the FAA50 group and groups that received deficient diets. The deficiency of singular IDAA did not induce significant changes in feed intake; however, the combined deficiency in the Def diet caused a significant increase in feed intake. This increased feed intake led to decreased feeding efficiency. A significant decrease in feeding efficiency was also observed in the (-) Lys group. There was an observed upregulation of neuropeptide Y (NPY), an orexigenic hormone, in the Def group. Overall, results from this study suggest stomachless fish increase feed intake when challenged with IDAA-deficient diets, and the regulation of NPY might play a role in this response.

Effects of exogenous ghrelin treatment on oxidative stress, inflammation and histological parameters in a fat-fed streptozotocin rat model.

In this study, the anti-inflammatory, antioxidative, and protective effects of ghrelin were investigated in a fat-fed streptozotocin (STZ) rat model and compared with metformin, diabetes and the healthy control groups. Histopathological evaluations were performed on H&E-stained pancreas and brain sections. Biochemical parameters were investigated by enzyme-linked immunosorbent assay. Blood glucose levels were significantly decreased with ghrelin or metformin treatments than the diabetes group. STZ administration increased brain, renal and pancreatic IL-1ß, TNF-α and MDA while decreasing GPX, CAT, SOD, and NGF levels. Ghrelin increased renal GPX, CAT, NGF pancreatic GPX, SOD, CAT, NGF and brain SOD, NGF while it decreased renal, pancreatic and brain IL-1ß, TNF-α and MDA levels. Ghrelin reduced neuronal loss and degeneration in the cerebral cortex and hippocampus and greatly ameliorated diabetes-related damage in pancreas. In conclusion, the data suggested that ghrelin is an effective candidate as a protectant for reducing the adverse effects of diabetes.

Vasopressin differentially modulates the excitability of rat olfactory bulb neuron subtypes.

Vasopressin (VP) plays a crucial role in social memory even at the level of the olfactory bulb (OB), where OB VP cells are activated during social interactions. However, it remains unclear how VP modulates olfactory processing to enable enhanced discrimination of very similar odors, e.g., rat body odors. Thus far, it has been shown that VP reduces firing rates in mitral cells (MCs) during odor presentation in vivo and decreases the amplitudes of olfactory nerve-evoked excitatory postsynaptic potentials (ON-evoked EPSPs) in external tufted cells in vitro. We performed whole-cell patch-clamp recordings and population Ca2+ imaging on acute rat OB slices. We recorded ON-evoked EPSPs as well as spontaneous inhibitory postsynaptic currents (IPSCs) from two types of projection neurons: middle tufted cells (mTCs) and MCs. VP bath application reduced the amplitudes of ON-evoked EPSPs and the frequencies of spontaneous IPSCs in mTCs but did not change those in MCs. Therefore, we analyzed ON-evoked EPSPs in inhibitory interneurons, i.e., periglomerular cells (PGCs) and granule cells (GCs), to search for the origin of increased inhibition in mTCs. However, VP did not increase the amplitudes of evoked EPSPs in either type of interneurons. We next performed two-photon population Ca2+ imaging in the glomerular layer and the superficial GC layer of responses to stronger ON stimulation than during patch-clamp experiments that should evoke action potentials in the measured cells. We observed that VP application increased ON-evoked Ca2+ influx in juxtaglomerular cells and GC somata. Thus, our findings indicate inhibition by VP on projection neurons via strong ON input-mediated inhibitory interneuron activity. This neural modulation could improve representation of odors, hence, better discriminability of similar odors, e.g., conspecific body odors.

The complex neurochemistry of the cockroach antennal heart.

The innervation of the antennal heart of the cockroach Periplaneta americana was studied with immunocytochemical techniques on both the light and electron microscopic levels. The antennal heart is innervated by two efferent systems, both using one biogenic amine in combination with neuropeptides. In one, we found co-localization of serotonin with proctolin and allatostatin. These fibers most likely originate from paired neurons located in the suboesophageal ganglion. In the second system, we found octopamine co-localized with the short neuropeptide F. The source of this second system is dorsal unpaired median (DUM) neurons, also located in the suboesophageal ganglion. The possible effects of these neuromediators on different targets are discussed.

Tear neuropeptide Y as a non-invasive marker of peripheral microvascular complications in type 1 diabetes.

AIMS: To investigate tear neuropeptide Y (NPY) and substance P concentrations in individuals with type 1 diabetes, comparing those with and without both diabetic retinopathy (DR) and peripheral neuropathy. METHODS: This cross-sectional study involved 41 participants with type 1 diabetes and none to moderate DR, and 22 healthy controls. Assessments included clinical ocular surface parameters, quantification of corneal nerve attributes (based on in vivo confocal microscopy imaging), DR grading, and evaluation for small and large fibre neuropathy. Concentrations of NPY and substance P in tear samples were measured using enzyme-linked immunosorbent assay. RESULTS: Mean (± standard deviation) tear NPY concentrations in participants with type 1 diabetes and length-dependent small fibre neuropathy (SFN) was lower than in controls (10.84 ± 4.10 ng/mL vs 14.72 ± 3.12 ng/mL; p=0.004), but not significantly different from type 1 diabetes participants without SFN (13.39 ± 4.66 ng/mL; p=0.11). Tear NPY levels were lower in individuals with type 1 diabetes and mild/moderate non-proliferative DR (10.44 ± 3.46 ng/mL) compared to none/minimal DR (13.79 ± 4.76 ng/mL; p=0.0005) and controls. In separate linear regression models, both the presence of SFN (ß = -0.75, p=0.02) and the presence of mild/moderate DR (ß = -0.84, p=0.009) were significantly associated with tear NPY levels relative to controls, after adjusting for participant age, sex, and dry eye disease. There were no inter-group differences for tear substance P concentrations. CONCLUSIONS: Tear NPY has potential utility as an indicator of peripheral microvascular complications associated with type 1 diabetes.

Anthropogenic electromagnetic radiation alters the transcription levels of the genes encoding the SIFamide and myoinhibitory peptide and their receptors in Ixodes ricinus synganglion.

The research of the influences of man-made electromagnetic fields on tick physiology has been very sparse and long neglected since the pioneer studies published in 1996 and 2000. Once multiple behavioral tests confirmed an attraction and possible perception of electromagnetic fields in ticks, a new interest in this topic erupted in recent years. In this study, qRT-PCR is utilized to determine the changes in the mRNA transcript levels of neuropeptides SIFamide and myoinhibitory peptide (mip and sifa) and their representative receptors (mip-r1 and sifa-r1) in the synganglia of the tick Ixodes ricinus irradiated by 900 MHz radiofrequency electromagnetic field. It was determined that 40 V/m intensity has a significant suppressory effect on the transcript levels of all genes after at least 60 minutes of constant exposure in both sexes. Commonly occurring intensity of radiation in urban areas (2 V/m) produced an elevation in mRNA levels after various timespans in every gene. A significant decrease of transcript abundances was detected in females after one hour of exposure to 2 V/m. Results of this study widen the knowledge of EMF-induced alterations in the neurophysiology of I. ricinus, the most commonly distributed hard tick in Europe.

Late maternal separation provides resilience to chronic variable stress-induced anxiety- and depressive-like behaviours in male but not female mice.

Maternal separation can have long-lasting effects on an individual's susceptibility to stress later in life. Maternal separation during the postnatal period is a commonly used paradigm in rodents to investigate the effects of early life stress on neurobehavioural changes and stress responsiveness. However, maternal separation during stress hyporesponsive and responsive periods of postnatal development may differ in its effects on stress resilience. Therefore, we hypothesised that late maternal separation (LMS) from postnatal day 10 to 21 in mice may have different effect on resilience than early maternal separation during the first week of postnatal life. Our results suggested that male LMS mice are more resilient to chronic variable stress (CVS)-induced anxiety and depressive-like behaviour as confirmed by the open field, light-dark field, elevated plus maze, sucrose preference and tail suspension tests. In contrast, female LMS mice were equally resilient as non-LMS female mice. We found increased expression of NPY, NPY1R, NPY2R, NPFFR1, and NPFFR2 in the hypothalamus of male LMS mice whereas the opposite effect was observed in the hippocampus. LMS in male and female mice did not affect circulating corticosterone levels in response to psychological or physiological stressors. Thus, LMS renders male mice resilient to CVS-induced neurobehavioural disorders in adulthood.

Sexual dimorphism exists in the effects of late maternal separation (LMS)LMS provides resilience to stress-induced anxiety and depression in male miceLMS upregulates NPY and NPVF system in the hypothalamus of male miceNo effect of LMS on stress-induced corticosterone levels.

Neuromodulator-induced temperature robustness in a motor pattern: a comparative study between two decapod crustaceans.

While temperature fluctuations pose significant challenges to the nervous system, many vital neuronal systems in poikilothermic animals function over a broad temperature range. Using the gastric mill pattern generator in the Jonah crab, we previously demonstrated that temperature-induced increases in leak conductance disrupt neuronal function and that neuropeptide modulation provides thermal protection. Here, we show that neuropeptide modulation also increases temperature robustness in Dungeness and green crabs. As in Jonah crabs, higher temperatures increased leak conductance in both species' pattern-generating lateral gastric neuron and terminated rhythmic gastric mill activity. Likewise, increasing descending modulatory projection neuron activity or neuropeptide transmitter application rescued rhythms at elevated temperatures. However, decreasing input resistance using dynamic clamp only restored the rhythm in half of the experiments. Thus, neuropeptide modulation increased temperature robustness in both species, demonstrating that neuropeptide-mediated temperature compensation is not limited to one species, although the underlying cellular compensation mechanisms may be distinct.

Expression and localization of the neuropeptide Y-Y4 receptor in the chick spleen: mRNA upregulation by high ambient temperature.

High ambient temperatures (HT) can increase diencephalic neuropeptide Y (NPY) expression, and central injection of NPY attenuates heat stress responses while inducing an antioxidative state in the chick spleen. However, there is a lack of knowledge about NPY receptor expression, and its regulation by HT, in the chick spleen. In the current study, male chicks were used to measure the expression of NPY receptors in the spleen and other immune organs under acute (30 vs. 40 ± 1°C for 3 h) or chronic (30 vs. 40 ± 1°C for 3 h/day for 3 days) exposure to HT and in response to central injection of NPY (47 pmol, 188 pmol, or 1 nmol). We found that NPY-Y4 receptor mRNA was expressed in the spleen, but not in other immune organs studied. Immunofluorescence staining revealed that NPY-Y4 receptors were localized in the splenic pulp. Furthermore, NPY-Y4 receptor mRNA increased in the chick spleen under both acute and chronic exposure to HT. Central NPY at two dose levels (47 and 188 pmol) and a higher dose (1 nmol) did not increase splenic NPY-Y4 receptor mRNA expression or splenic epinephrine under HT (35 ± 1°C), and significantly increased 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations under HT (40 ± 1°C). In conclusion, increased expression of NPY-Y4 receptor mRNA in the spleen under HT suggest that Y4 receptor may play physiological roles in response to HT in male chicks.

Distinct Neuromodulatory Effects of Endogenous Orexin and Dynorphin Corelease on Projection-Defined Ventral Tegmental Dopamine Neurons.

Dopamine (DA) neurons in the ventral tegmental area (VTA) respond to motivationally relevant cues, and circuit-specific signaling drives different aspects of motivated behavior. Orexin (ox; also known as hypocretin) and dynorphin (dyn) are coexpressed lateral hypothalamic (LH) neuropeptides that project to the VTA. These peptides have opposing effects on the firing activity of VTADA neurons via orexin 1 (Ox1R) or kappa opioid (KOR) receptors. Given that Ox1R activation increases VTADA firing, and KOR decreases firing, it is unclear how the coreleased peptides contribute to the net activity of DA neurons. We tested if optical stimulation of LHox/dyn neuromodulates VTADA neuronal activity via peptide release and if the effects of optically driven LHox/dyn release segregate based on VTADA projection targets including the basolateral amygdala (BLA) or the lateral or medial shell of the nucleus accumbens (lAcbSh, mAchSh). Using a combination of circuit tracing, optogenetics, and patch-clamp electrophysiology in male and female orexincre mice, we showed a diverse response of LHox/dyn optical stimulation on VTADA neuronal firing, which is not mediated by fast transmitter release and is blocked by antagonists to KOR and Ox1R signaling. Additionally, where optical stimulation of LHox/dyn inputs in the VTA inhibited firing of the majority of BLA-projecting VTADA neurons, optical stimulation of LHox/dyn inputs in the VTA bidirectionally affects firing of either lAcbSh- or mAchSh-projecting VTADA neurons. These findings indicate that LHox/dyn corelease may influence the output of the VTA by balancing ensembles of neurons within each population which contribute to different aspects of reward seeking.

Discovery of a neuropeptide that acts as an autotomy-promoting factor.

One of the most remarkable adaptations to survive attacks from predators is to detach an appendage-a process known as autotomy. This occurs in a variety of animals, including lizards (tail), crabs (legs), and starfish (arms). There has been extensive investigation of the evolution, ecology, and biomechanical impact of autotomy,1,2,3 but little is known about neural mechanisms controlling autotomy in animals. However, evidence for the existence of a peptide that acts as an autotomy-promoting factor in starfish has been reported.4 While investigating in vivo effects of a sulfakinin/cholecystokinin-type neuropeptide (ArSK/CCK1) in the starfish Asterias rubens,5,6 we observed that this peptide triggered arm autotomy in some animals. Furthermore, when injection of ArSK/CCK1 was combined with mechanical clamping of an arm, autotomy of the clamped arm occurred in 85% of animals tested, with 46% also autotomizing one or more other arms. In contrast, no autotomy was observed in clamped animals that were injected with water (control). To examine the physiological relevance of these findings, we analyzed expression of ArSK/CCK1 in the autotomy plane, a specialized region at the base of the arms in A. rubens.7,8 In accordance with its in vivo effects, nerve fibers expressing ArSK/CCK1 were revealed in the tourniquet muscle, a band of muscle that mediates constriction of the arm during and after autotomy. We conclude that ArSK/CCK1 acts as an autotomy-promoting factor in starfish and as such it is the first neuropeptide to be identified as a regulator of autotomy in animals.

Isolation and characterization of NGFFYamide neuropeptide from Patiria pectinifera pyloric caeca extract.

Neuropeptides are small molecules that mediate intercellular signaling and regulate physiological processes. Starfish possess various myoactive neuropeptides, including starfish myorelaxant peptide (SMP) and a calcitonin-type peptide with apical muscle relaxing properties. In this study, we report the purification of a neuropeptide from starfish (Patiria pectinifera) pyloric caeca extract using high-performance liquid chromatography (HPLC) and an in vitro bioassay to screen for fractions and peptides with relaxing effects on P. pectinifera apical muscle preparations. A series of HPLC steps using reversed-phase and cation-exchange columns yielded a purified peptide with muscle-relaxing effects. The purified peptide's structure was determined by LC-MS and Edman degradation, revealing a pentapeptide with an amidated C-terminus (NGFFYamide) and a molecular mass of 646.2930 Da. This is the first report of NGFFYamide purification from P. pectinifera through biochemical methods. The nucleotide sequence encoding the NGFFYamide precursor was determined, showing the presence of a conserved neurophysin domain in the C-terminal region. RT-qPCR results confirmed high expression in radial nerves cord, consistent with previous findings on NG peptides in echinoderms. In vitro pharmacological studies on muscle preparations from P. pectinifera and Asterias amurensis revealed differential relaxing activity of NGFFYamide on apical muscles, while its effects on tube foot preparations were similar in both species. NGFFYamide also induced potent contraction in P. pectinifera cardiac stomach. Comparison of three NG peptides (NGFFYamide, NGFFFamide, and NGIWYamide) on P. pectinifera cardiac stomach revealed varying potency, suggesting class-specific receptor interactions. Tachyphylaxis was observed in P. pectinifera apical muscle but not in A. amurensis, warranting further investigation. Based on these results, it is plausible that NGFFYamide could be involved in regulating locomotion and feeding behavior in P. pectinifera, consistent with findings in Asterias rubens.

Neuropeptide Y receptor activation preserves inner retinal integrity through PI3K/Akt signaling in a glaucoma mouse model.

Neuropeptide Y (NPY), an endogenous peptide composed of 36 amino acids, has been investigated as a potential therapeutic agent for neurodegenerative diseases due to its neuroprotective attributes. This study investigated the neuroprotective effects of NPY in a mouse model of glaucoma characterized by elevated intraocular pressure (IOP) and progressive retinal ganglion cell degeneration. Elevated IOP in mice was induced through intracameral microbead injections, accompanied by intravitreal administration of NPY peptide. The results demonstrated that NPY treatment preserved both the structural and functional integrity of the inner retina and mitigated axonal damage and degenerative changes in the optic nerve under high IOP conditions. Further, NPY treatment effectively reduced inflammatory glial cell activation, as evidenced by decreased expression of glial fibrillary acidic protein and Iba-1. Notably, endogenous NPY expression and its receptors (NPY-Y1R and NPY-Y4R) levels were negatively affected in the retina under elevated IOP conditions. NPY treatment restored these changes to a significant extent. Molecular analysis revealed that NPY mediates its protective effects through the mitogen-activated protein kinase (MAPK) and PI3K/Akt signaling pathways. These findings highlight the therapeutic potential of NPY in glaucoma treatment, underscoring its capacity to preserve retinal health, modulate receptor expression under stress, reduce neuroinflammation, and impart protection against axonal impairment.

Functional expression and characterization of CAPA receptor in the digestive tract and life stages of Drosophila suzukii, and differential activities with insect PRXamide peptides.

Spotted-wing drosophila, Drosophila suzukii (Matsumura), is an invasive vinegar fly that is a major threat to the small fruits industries globally. Insect capa genes encode multiple neuropeptides, including CAPA-periviscerokinin (CAPA-PVK) peptides, that are specifically known to cause diuresis or anti-diuresis in various organisms. Here we identified and characterized a corresponding G protein-coupled receptor (GPCR) of the D. suzukii CAPA-PVK peptides: CAPA receptor (CAPA-R). To better characterize the behavior of D. suzukii CAPA-R, we used insect cell-based functional expression assays to evaluate responses of CAPA-R against D. suzukii CAPA-PVKs, CAPA-PVKs from five species in Insecta, one species from Mollusca, modified CAPA-PVK peptides, and some PRXamide family peptides: pyrokinin (PK), diapause hormone (DH), and ecdysis-triggering hormone (ETH). Functional studies revealed that the D. suzukii CAPA-R is strongly activated by both of its own natural D. suzukii CAPA-PVKs, and interestingly, it was strongly activated by other CAPA-PVK peptides from Frankliniella occidentallis (Thysanoptera), Solenopsis invicta (Hymenoptera), Helicoverpa zea (Lepidoptera) and Plutella xylostella (Lepidoptera). However, D. suzukii CAPA-R was not activated by Mollusca CAPA-PVK or the other PRXamide peptides. Gene expression analyses showed that the CAPA-R was highly expressed in the Malpighian tubules and moderately in hindgut compared to other digestive organs or the rest of body, supporting diuretic/antidiuretic functionality. When compared across life stages of D. suzukii, expression of CAPA-R was approximately 1.5x greater in the third instar than the other stages and minimally detected in the eggs, 4-day old pupae and 3-day old adults. Our results functionally characterized the D. suzukii CAPA-R and a few short peptides were identified as potential biological targets to exploit the CAPA-R for D. suzukii management.

Insect-derived extracts and peptides in neuroprotection.

Throughout history, various cultures have recognized the significance of insects and have integrated them into traditional medicinal practices. In addition to medicines, insects are garnering attention as a sustainable and nutritious dietary alternative. Although edible insects have long been recognized as food sources in many Asian cultures, recent scientific studies have highlighted their potential therapeutic benefits, particularly in the field of neuroprotection. This review explores insect-derived extracts and peptides, elucidating their neuroprotective potential. This review highlights the potential use of insects as a source of neuroprotective agents. Advancements in neuroprotection may find a key ally in insects as our understanding of the symbiotic relationship between insects and human health becomes more profound.

Allatotropin (AT) related peptides L-ATRP and D2-ATRP diastereomers activate an endogenous receptor and suppress heart rate in the Pacific abalone Haliotis discus hannai.

Allatotropin (AT) has been identified in many insects and plays important roles in the regulation of their intestinal contraction, heart rate, ion transport, and digestive enzyme secretion. However, information on AT-related bioinformatics in other animal phyla is scarce. In this study, we cloned a full-length cDNA encoding the AT-related peptide receptor (ATRPR) of the abalone Haliotis discus hannai (Hdh) and further characterized Hdh-ATRPR with its potential ligands, Hdh-ATRPs. In luciferase reporter and Ca2+ mobilization assays, Hdh-ATRPs, including a D-type Phe at the second amino acid position, Hdh-D2-ATRP, activated Hdh-ATRPR in a dose-dependent manner, whereas all-L-type Hdh-ATRP was a more potent ligand than Hdh-D2-ATRP. Furthermore, Hdh-ATRPs induced ERK1/2 phosphorylation in Hdh-ATRPR-expressing HEK293 cells, which was dose-dependently abolished by the PKC inhibitor Gö6983. The heart rate decreased significantly within 10 min when Hdh-D2-ATRP was injected into the adduct muscle sinus of abalone (0.2 or 1.0 µg/g body weight), while the abalone injected with a high concentration of Hdh-D2-ATRP (1.5 µg/g body weight) were sublethal within 5 h. Thus, Hdh-ATRP signaling is primarily linked to the Gαq/PKC and is possibly associated with heart rate regulation in abalone.