ABSTRACT
Epilepsy, a neurological disorder characterized by excessive neuronal activity and synchronized electrical discharges, ranks among the most prevalent global neurological conditions. Despite common use, antiepileptic drugs often result in adverse effects and lack effectiveness in controlling seizures in temporal lobe epilepsy (TLE) patients. Recent research explored the potential of occidentalin-1202, a peptide inspired by Polybia occidentalis venom, in safeguarding Wistar rats from chemically induced seizures. The present study evaluated the new analog from occidentalin-1202 named NOR-1202 using acute and chronic pilocarpine-induced models and an acute kainic acid (KA) male mice model. NOR-1202 was administered through the intracerebroventricular (i.c.v.), subcutaneous, or intraperitoneal routes, with stereotaxic procedures for the i.c.v. injection. In the acute pilocarpine-induced model, NOR-1202 (i.c.v.) protected against generalized seizures and mortality but lacked systemic antiepileptic activity. In the KA model, it did not prevent generalized seizures but improved survival. In the chronic TLE model, NOR-1202's ED50 did not differ significantly from the epileptic or healthy groups regarding time spent in spontaneous recurrent seizures during the five-day treatment. However, the NOR-1202 group exhibited more seizures than the healthy group on the second day of treatment. In summary, NOR-1202 exhibits antiepileptic effects against chemoconvulsant-induced seizures, but no effect was observed when administered systemically.
Subject(s)
Anticonvulsants , Disease Models, Animal , Seizures , Animals , Male , Anticonvulsants/pharmacology , Anticonvulsants/therapeutic use , Mice , Seizures/drug therapy , Seizures/chemically induced , Pilocarpine , Kainic Acid/analogs & derivatives , Peptides/pharmacology , Peptides/therapeutic use , Peptides/administration & dosage , Epilepsy, Temporal Lobe/drug therapy , Epilepsy, Temporal Lobe/chemically inducedABSTRACT
Parkinson's disease (PD) is the second most common neurodegenerative disease globally. Current drugs only alleviate symptoms without halting disease progression, making rodent models essential for researching new therapies and understanding the disease better. However, selecting the right model is challenging due to the numerous models and protocols available. Key factors in model selection include construct, face, and predictive validity. Construct validity ensures the model replicates pathological changes seen in human PD, focusing on dopaminergic neurodegeneration and a-synuclein aggregation. Face validity ensures the model's symptoms mirror those in humans, primarily reproducing motor and non-motor symptoms. Predictive validity assesses if treatment responses in animals will reflect those in humans, typically involving classical pharmacotherapies and surgical procedures. This review highlights the primary characteristics of PD and how these characteristics are validated experimentally according to the three criteria. Additionally, it serves as a valuable tool for researchers in selecting the most appropriate animal model based on established validation criteria.
Subject(s)
Disease Models, Animal , Parkinson Disease , Animals , Parkinson Disease/metabolism , Parkinson Disease/pathology , Humans , Rodentia , alpha-Synuclein/metabolism , Reproducibility of ResultsSubject(s)
Gait Disorders, Neurologic , Neurotransmitter Agents , Parkinson Disease , Humans , Parkinson Disease/complications , Parkinson Disease/physiopathology , Gait Disorders, Neurologic/etiology , Gait Disorders, Neurologic/physiopathology , Neurotransmitter Agents/metabolism , Cognition/physiologyABSTRACT
The pharmacological treatment of epilepsy is often complex due to the lack of efficacy in many patients and profound side effects from current drugs, including sedation, motor impairment, and teratogenesis. In the quest for new antiepileptic drugs, animal venoms offer a valuable source of neuroactive molecules targeting ion channels and neurotransmitter receptors. This study investigates the antiepileptic potential of compounds isolated from the venom of the Parawixia bistriata spider. One compound, designated Parawixin-11, demonstrated significant anticonvulsant effects when injected into the cerebral ventricle in a dose-response manner. It effectively countered seizures induced by bicuculline (ED50 0.16 µg/animal), pentylenetetrazole (ED50 0.08 µg/animal), strychnine (ED50 0.05 µg/animal), pilocarpine (ED50 0.10 µg/animal), and NMDA (ED50 0.008 µg/animal). We also assessed whether intracerebroventricular administration of Parawixin-11 caused motor or cognitive impairments in rats using the open field, rotarod, and Morris water maze tests. No differences in exploration or movement were observed with doses of 0.3, 0.2, or 0.1 µg of Parawixin-11. Although there was an increased latency to find the platform during the acquisition phase of the Morris water maze test, no differences in spatial memory retention were noted. Given Parawixin-11's potency against NMDA-induced seizures, we hypothesize that it may modulate the glutamatergic system, aligning with the mechanisms of several spider-derived polyamines.
ABSTRACT
Gut dysbiosis is linked to metabolic and neurodegenerative diseases and comprises a plausible link between high-fat diet (HFD) and brain dysfunction. Here we show that gut microbiota modulation by either antibiotic treatment for 5 weeks or a brief 3-day fecal microbiota transplantation (FMT) regimen from low-fat (control) diet-fed mice decreased weight gain, adipose tissue hypertrophy, and glucose intolerance induced by HFD in C57BL/6 male mice. Notably, gut microbiota modulation by FMT completely reversed impaired recognition memory induced by HFD, whereas modulation by antibiotics had less pronounced effect. Improvement in recognition memory by FMT was accompanied by decreased HFD-induced astrogliosis in the hippocampal cornu ammonis region. Gut microbiome composition analysis indicated that HFD diminished microbiota diversity compared to control diet, whereas FMT partially restored the phyla diversity. Our findings reinforce the role of the gut microbiota on HFD-induced cognitive impairment and suggest that modulating the gut microbiota may be an effective strategy to prevent metabolic and cognitive dysfunction associated with unfavorable dietary patterns.
Subject(s)
Diet, High-Fat , Fecal Microbiota Transplantation , Gastrointestinal Microbiome , Memory Disorders , Mice, Inbred C57BL , Animals , Diet, High-Fat/adverse effects , Fecal Microbiota Transplantation/methods , Male , Memory Disorders/prevention & control , Memory Disorders/etiology , Mice , Gastrointestinal Microbiome/physiology , Hippocampus , Glucose IntoleranceABSTRACT
Venom-derived peptides are important sources for the development of new therapeutic molecules, especially due to their broad pharmacological activity. Previously, our research group identified a novel natural peptide, named fraternine, with promising effects for the treatment of Parkinson's disease. In the present paper, we synthesized three peptides bioinspired in fraternine: fra-10, fra-14, and fra-24. They were tested in the 6-OHDA-induced model of parkinsonism, quantifying motor coordination, levels of TH+ neurons in the substantia nigra pars compacta (SN), and inflammation mediators TNF-α, IL-6, and IL-1ß in the cortex. Peptides fra-14 and fra-10 improved the motor coordination in relation to 6-OHDA lesioned animals. However, most of the peptides were toxic in the doses applied. All three peptides reduced the intensity of the lesion induced rotations in the apomorphine test. Fra-24 higher dose increased the number of TH+ neurons in SN and reduced the concentration of TNF-α in the cortex of 6-OHDA lesioned mice. Overall, only the peptide fra-24 presented a neuroprotection effect on dopaminergic neurons of SN and a reduction of cytokine TNF-α levels, making it worthy of consideration for the treatment of PD.
Subject(s)
Parkinson Disease , Mice , Animals , Parkinson Disease/drug therapy , Oxidopamine , Tumor Necrosis Factor-alpha , Substantia Nigra , Antiparkinson Agents/pharmacology , Antiparkinson Agents/therapeutic use , Dopaminergic Neurons , Disease Models, AnimalABSTRACT
Idiopathic pulmonary fibrosis (IPF) is a progressive, relentless, and deadly disease. Little is known about its pathogenetic mechanisms; therefore, developing efficient pharmacological therapies is challenging. This work aimed to apply a therapeutic alternative using immunomodulatory peptides in a chronic pulmonary fibrosis murine model. BALB/c mice were intratracheally instilled with bleomycin (BLM) and followed for 30 days. The mice were treated with the immune modulatory peptides ToAP3 and ToAP4 every three days, starting on the 5th day post-BLM instillation. ELISA, qPCR, morphology, and respiratory function analyses were performed. The treatment with both peptides delayed the inflammatory process observed in the non-treated group, which showed a fibrotic process with alterations in the production of collagen I, III, and IV that were associated with significant alterations in their ventilatory mechanics. The ToAP3 and ToAP4 treatments, by lung gene modulation patterns, indicated that distinct mechanisms determine the action of peptides. Both peptides controlled the experimental IPF, maintaining the tissue characteristics and standard function properties and regulating fibrotic-associated cytokine production. Data obtained in this work show that the immune response regulation by ToAP3 and ToAP4 can control the alterations that cause the fibrotic process after BLM instillation, making both peptides potential therapeutic alternatives and/or adjuvants for IPF.
Subject(s)
Idiopathic Pulmonary Fibrosis , Lung , Mice , Animals , Lung/pathology , Idiopathic Pulmonary Fibrosis/drug therapy , Idiopathic Pulmonary Fibrosis/pathology , Peptides/pharmacology , Peptides/therapeutic use , Bleomycin , Collagen Type I , Mice, Inbred C57BLABSTRACT
The impact of overnutrition early in life is not restricted to the onset of cardiovascular and metabolic diseases, but also affects critical brain functions related to cognition. This study aimed to evaluate the relationship between peripheral metabolic and bioenergetic changes induced by a two-hit protocol and their impact on cognitive function in juvenile mice. Three-week-old male C57BL/6 mice received a high-fat diet (HFD) or control diet for 7 weeks, associated with two low doses of streptozotocin (STZ) or vehicle. Despite the absence of obesity, HFD+STZ impaired glucose metabolism and induced a trend towards cholesterol increase. The two-hit protocol impaired recognition and spatial memories in juvenile mice, without inducing a depressive-like behavior. HFD+STZ mice presented increased immunoreactivity for GFAP and a trend towards a decrease in NeuN in the hippocampus. The treatment caused a bioenergetic impairment in the hippocampus, characterized by a decrease in both O2 consumption related to ATP production and in the maximum respiratory capacity. The thermogenic capacity of brown adipose tissue was impaired by the two-hit protocol, here verified through the absence of a decrease in O2 consumption after uncoupled protein-1 inhibition and an increase in the reserve respiratory capacity. Impaired mitochondrial function was also observed in the liver of HFD+STZ juvenile mice, but not in their heart. These results indicate that exposure to HFD+STZ early in life has a detrimental impact on the bioenergetic and mitochondrial function of tissues with metabolic and thermogenic activities, which is likely related to hippocampal metabolic changes and cognitive impairment.
Subject(s)
Cognition , Obesity , Mice , Male , Animals , Mice, Inbred C57BL , Obesity/metabolism , Diet, High-Fat/adverse effects , Mitochondria/metabolismABSTRACT
The ability of venom-derived peptides to disrupt physiological processes in mammals provides an exciting source for pharmacological development. Our research group has identified a new class of neuroactive peptides from the venom of a Brazilian social wasp, Polybia occidentalis, with the potential pharmacological profile to treat epilepsies. The study was divided into five phases: Phase 1 concerned the extraction, isolation and purification of Occidentalin-1202(n) from the crude venom, followed by the synthesis of an identical analogue peptide, named Occidentalin-1202(s). In Phase 2, we described the effects of both peptides in two acute models of epilepsy-kainic acid and pentylenetetrazole-induced model of seizures-and measured estimated ED50 and therapeutic index values, electroencephalographic studies and C-fos evaluation. Phase 3 was a compilation of advanced tests performed with Occidentalin-1202(s) only, reporting histopathological features and its performance in the pilocarpine-induced status epilepticus. After the determination of the antiepileptic activity of Occidentalin-1202(s), Phase 4 consisted of evaluating its potential adverse effects, after chronic administration, on motor coordination (Rotarod) and cognitive impairment (Morris water maze) tests. Finally, in Phase 5, we proposed a mechanism of action using computational models with kainate receptors. The new peptide was able to cross the blood-brain barrier and showed potent antiseizure effects in acute (kainic acid and pentylenetetrazole) and chronic (temporal lobe epilepsy model induced by pilocarpine) models. Motor and cognitive behaviour were not adversely affected, and a potential neuroprotective effect was observed. Occidentalin-1202 can be a potent blocker of the kainate receptor, as assessed by computational analysis, preventing glutamate and kainic acid from binding to the receptor's active site. Occidentalin-1202 is a peptide with promising applicability to treat epilepsy and can be considered an interesting drug model for the development of new medicines.
ABSTRACT
Deep brain stimulation (DBS) appeared in the therapeutic framework for Parkinson's disease in the late 1980 s and early 1990 s, conceived as an alternative to ablative treatments, using inhibitory electrical stimulation parameters still clinically in force today, with frequencies above 130 Hz, a pulse width of 60 ms and current intensity around 3 mA into deep brain structures, to relieve the motor symptoms of the disease. This context expands into a technique not only restricted to the targets traditionally used in lesional procedures, supported by the knowledge acquired with non-human primate (NHP) animal models during the early 1990 s, initiated by Benazzouz and collaborators. Currently, NHP animal models have lost ground to research models in rodents, which have assumed a prominent position in scientific research on DBS. However, how can an animal so small and different from Homo sapiens provide relevant information that may guide the evolution of treatment for a condition that occurs only in humans, like PD? The scope of this review is to address recent advances in PD pathogeny, DBS principles, and different in vivo experimental DBS models in rodents, their limitations and relevance, as well as the future directions in animal models for scientific research.
Subject(s)
Deep Brain Stimulation , Parkinson Disease , Animals , Brain , Deep Brain Stimulation/methods , Humans , Parkinson Disease/therapy , Primates , RodentiaABSTRACT
Antiepileptic drugs have been successfully treating epilepsy and providing individuals sustained seizure freedom. However, about 30% of the patients with epilepsy present drug resistance, which means they are not responsive to the pharmacological treatment. Considering this, it becomes extremely relevant to pursue alternative therapeutic approaches, in order to provide appropriate treatment for those patients and also improve their quality of life. In the light of that, this review aims to discuss some innovative options for the treatment of epilepsy, which are currently under investigation, addressing strategies that go from therapeutic compounds to clinical procedures. For instance, peptides derived from animal venoms, such as wasps, spiders, and scorpions, demonstrate to be promising antiepileptic molecules, acting on a variety of targets. Other options are cannabinoids and compounds that modulate the endocannabinoid system, since it is now known that this network is involved in the pathophysiology of epilepsy. Furthermore, neurostimulation is another strategy, being an alternative clinical procedure for drug-resistant patients who are not eligible for palliative surgeries.
Subject(s)
Cannabinoids , Epilepsy , Animals , Anticonvulsants/therapeutic use , Cannabinoids/pharmacology , Cannabinoids/therapeutic use , Endocannabinoids , Epilepsy/drug therapy , Peptides , Quality of Life , Venoms/therapeutic useABSTRACT
Approximately 46.8 million people have been diagnosed worldwide with dementia, of which the most common type is Alzheimer's disease (AD). Since the current AD treatment is incipient and limited, it is essential to develop new drugs to prevent AD. Considering that evolutionary pressure selected animal venom compounds that are very specific for a unique target, those can be a potential drug against AD. Octovespin was modified from occidentalin-1202, which is a peptide isolated from Polybia occidentalis wasp venom. In this context, this study evaluated the effect of treatment with octovespin against Amyloid-ß (Aß)-induced toxicity, which is postulated to be one of the main causes of AD, in both in vitro and in vivo tests. In vitro, octovespin was able to prevent Aß aggregation in a ThT assay. In vivo, octovespin (0.15 nmol/animal) reverses memory impairment that is due to Aß toxicity, in the Morris Water Maze and Novel Object Recognition Test. Our results suggested that octovespin is a potential drug for the treatment of AD, due to its ability to avoid Aß aggregation in vitro and to prevent Aß -induced memory deficit in mice.
Subject(s)
Alzheimer Disease , Alzheimer Disease/drug therapy , Amyloid beta-Peptides/pharmacology , Animals , Cognition , Disease Models, Animal , Humans , Maze Learning , Memory Disorders/chemically induced , Memory Disorders/drug therapy , Memory Disorders/prevention & control , Mice , Mice, Transgenic , Peptide Fragments/pharmacology , Peptide Fragments/therapeutic use , Wasp Venoms/pharmacologyABSTRACT
One of the main obstacles in the treatment of neurological diseases, perhaps the biggest one, is the delivery of therapeutic compounds to the central nervous system, and nanoparticles are promising tools to overcome this challenge. Different types of nanoparticles may be used as delivery systems, including liposomes, carbon nanotubes, and dendrimers. Nevertheless, these nanoparticles must display characteristics to be useful in brain drug delivery, such as stability, permeability to blood vessels, biocompatibility, and specificity. All of these aspects are intrinsically related to the physicochemical properties of nanoformulations: size, composition, electric charge, hydrophobicity, mucoadherence, permeability to the blood-brain barrier, and many others. Furthermore, there are challenging hindrances involved in the development and application of nanoparticles - hence the importance of studying and understanding these pharmaceutical tools.
Subject(s)
Nanoparticles , Nanotubes, Carbon , Blood-Brain Barrier , Brain , Drug Delivery Systems , LiposomesABSTRACT
Parkinson's disease (PD) is a progressive and chronic neurodegenerative disease of the central nervous system. Early treatment for PD is efficient; however, long-term systemic medication commonly leads to deleterious side-effects. Strategies that enable more selective drug delivery to the brain using smaller dosages, while crossing the complex brain-blood barrier (BBB), are highly desirable to ensure treatment efficacy and decrease/avoid unwanted outcomes. Our goal was to design and test the neurotherapeutic potential of a forefront nanoparticle-based technology composed of albumin/PLGA nanosystems loaded with dopamine (ALNP-DA) in 6-OHDA PD mice model. ALNP-DA effectively crossed the BBB, replenishing dopamine at the nigrostriatal pathway, resulting in significant motor symptom improvement when compared to Lesioned and L-DOPA groups. Notably, ALNP-DA (20 mg/animal dose) additionally up-regulated and restored motor coordination, balance, and sensorimotor performance to non-lesioned (Sham) animal level. Overall, ALNPs represent an innovative, non-invasive nano-therapeutical strategy for PD, considering its efficacy to circumvent the BBB and ultimately deliver the drug of interest to the brain.
Subject(s)
Blood-Brain Barrier/metabolism , Dopamine/administration & dosage , Dopamine/pharmacokinetics , Drug Delivery Systems , Nanoparticles/administration & dosage , Parkinsonian Disorders/drug therapy , Parkinsonian Disorders/metabolism , Animals , Brain/drug effects , Brain/metabolism , Disease Models, Animal , Dopaminergic Neurons/drug effects , Humans , Male , Mice , Nanoparticles/chemistry , Nanoparticles/ultrastructure , Nanotechnology , Oxidopamine/toxicity , Parkinsonian Disorders/chemically induced , Particle Size , Polylactic Acid-Polyglycolic Acid Copolymer/chemistryABSTRACT
Parachartergus fraternus wasp induces inflammation with a predominance of mononuclear cells, that can acquire macrophage functions at the sting site, amplifying the response. These cells can be activated by venomous animals and are involved in destruction of injurious agents and release of inflammatory mediators. The objective of this work was to evaluate the activity of P. fraternus venom (Pfv) on isolated murine macrophage function. The cells were obtained from peritoneal cavity of Swiss male mice and incubated with Pfv (2.5, 5 and 10 µg/mL). Cytotoxicity was determined using MTT assay. Adhesion and detachment were evaluated using violet crystal dye. Spreading was evaluated based on morphological parameters. Phagocytosis was performed with opsonized zymosan. Production of hydrogen peroxide (H2O2) and nitric oxide (NO) were quantified using the phenol red and Griess assays, respectively. Pfv at concentrations evaluated was not cytotoxic in MTT assay and did not cause macrophage detachment in cell culture plates. However, it increased adhesion of macrophage, spreading and phagocytosis of opsonized zymosan, as well as induced production of H2O2 and NO. Therefore, Pfv induces macrophage activation in vitro and the response of these cells can be correlated with the previously reported inflammatory process triggered by this wasp.
Subject(s)
Macrophage Activation , Wasps , Animals , Hydrogen Peroxide/toxicity , Macrophages, Peritoneal , Male , Mice , Nitric Oxide , Phagocytosis , VenomsABSTRACT
Epilepsy is one of the most common neurological diseases in the world. The objective of this research was to investigate a new peptide from the venom of the social wasp Chartergellus communis useful to the study or pharmacotherapy of epilepsy. The wasps were collected, and their venom was extracted. Afterward, the steps of fractionation, sequencing, and identification were carried out to obtain four peptides. These molecules were synthesized for behavioral evaluation tests and electroencephalographic assays to determine their antiseizure potential (induction of acute seizures using the chemical compounds, pentylenetetrazole - PTZ, and pilocarpine - PILO) and analysis of neuropharmacological profile (general spontaneous activity and alteration in motor coordination). Chartergellus-CP1 (i.c.v. - 3.0 µg/animal) caused beneficial alterations in some of the parameters evaluated in both models: PTZ (latency and duration of maximum seizures) and PILO (latency and duration of, and protection against, maximum seizures, and reduction of the median of the seizure scores. When evaluated in 3 doses in the seizure model induced by PILO, the dose of 3.0 µg/animal protected the animals against seizures, with an estimated ED50 of 1.49 µg/animal. Electroencephalographic evaluation of Chartergellus-CP1 showed an improvement in latency, quantity, and percentage of protection against generalized electroencephalographic seizures in the PILO model. Further, Chartergellus-CP1 did not cause adverse effects on general spontaneous activity and motor coordination of animals. This study demonstrated how compounds isolated from wasps' venom may be important resources in the search for new drugs. Such compounds can be considered valuable therapeutic and biotechnological tools for the study and future treatment of epileptic disorders. In this context, a peptide that is potentially useful for epilepsy pharmacotherapy was identified in the venom of C. communis.
Subject(s)
Anticonvulsants/pharmacology , Wasp Venoms/pharmacology , Wasps , Animals , Anticonvulsants/therapeutic use , Disease Models, Animal , Pentylenetetrazole/therapeutic use , Pentylenetetrazole/toxicity , Peptides , Seizures/chemically induced , Seizures/drug therapyABSTRACT
Neurovespina is a synthetic peptide modified from Occidentalin-1202, a nine amino acid residue peptide isolated from the venom of the social wasp Polybia occidentalis. Previous studies showed that this peptide has a neuroprotective effect on the central nervous system, but its action on the eye has not been explored. So, the objective of this work was to investigate the neuroprotective effect of Neurovespina on the retina and its angiogenic potential in the chicken chorioallantoic membrane (CAM). Retinal ischemia was induced in rats by acute elevation of intraocular pressure (IOP). Electroretinography (ERG) measurements, histopathological and immunohistochemical analysis, and transmission electronic microscopy (TEM) records were performed to check the neuroprotection effect of Neurovespina in the retina of the animals. The angiogenic activity of the peptide was investigated by CAM assay. The results showed that Neurovespina was able to reduce the effects induced by ischemic injury, preventing the reduction of a- and b-waves in the scotopic ERG. Histopathological and immunohistochemistry assays showed that Neurovespina, mainly at 60 µg/ml, protected all layers of the retina. The CAM assay revealed that the peptide promoted the reduction of CAM vessels. So, Neurovespina was able to protect retinal cells from ischemic insult and has an antiangiogenic effect, which can be considered as a promising neuroprotective agent for intravitreal application.
Subject(s)
Ischemia/complications , Neuroprotective Agents/administration & dosage , Retinal Diseases/drug therapy , Retinal Diseases/pathology , Venoms/administration & dosage , Animals , Apoptosis/drug effects , Male , Neovascularization, Pathologic/drug therapy , Rats, Wistar , Retinal Diseases/etiology , Retinal Diseases/physiopathology , WaspsABSTRACT
The sting of different wasp species triggers local and systemic reactions in victims that can lead to death. Parachartergus fraternus is responsible for frequent accidents in Latin America; however, few studies have been conducted on this insect and its venom. In this study, the inflammatory process induced by the venom of the P. fraternus wasp (Pfv; 100, 200, and 400 µg/kg) was characterized. Mice were used to assess paw edema, vascular permeability, mast cell degranulation, leukocyte influx, nitric oxide (NO) production, expression of inflammatory genes, and histopathological changes. Pfv triggered edema formation with a peak dose of 200 µg/kg at 10 min. There was an increase in permeability in all periods and doses evaluated, with no differences between them. The 200 µg/kg dose induced mast cell degranulation in all periods, with a peak at 15 min. This same dose induced leukocyte influx with a predominance of mononuclear cells and triggered a peak in NO production in the 12th hour. The increase in COX-2, iNOS, and IFN-γ mRNA expression occurred after 1 and 6 h, and there was an increase in IL-10 expression after 48 h. In addition, Pfv triggered edema and induced an influx of macrophages and mast cells into the injection site. Therefore, Pfv induces an inflammatory process from the first 5 min of inoculation that can persist for up to 48 h.
Subject(s)
Wasp Venoms/toxicity , Wasps , Animals , Inflammation , VenomsABSTRACT
Parkinson's disease (PD) is a progressive neurodegenerative condition that affects the Central Nervous System (CNS). Insect venoms show high molecular variability and selectivity in the CNS of mammals and present potential for the development of new drugs for the treatment of PD. In this study, we isolated and identified a component of the venom of the social wasp Parachartergus fraternus and evaluated its neuroprotective activity in the murine model of PD. For this purpose, the venom was filtered and separated through HPLC; fractions were analyzed through mass spectrometry and the active fraction was identified as a novel peptide, called Fraternine. We performed two behavioral tests to evaluate motor discoordination, as well as an apomorphine-induced rotation test. We also conducted an immunohistochemical assay to assess protection in TH+ neurons in the Substantia Nigra (SN) region. Group treated with 10 µg/animal of Fraternine remained longer in the rotarod compared to the lesioned group. In the apomorphine test, Fraternine decreased the number of rotations between treatments. This dose also inhibited dopaminergic neuronal loss, as indicated by immunohistochemical analysis. This study identified a novel peptide able to prevent the death of dopaminergic neurons of the SN and recover motor deficit in a 6-OHDA-induced murine model of PD.