Lauren G. Singleton , Kelsey F. Thompson , Jordyn Carroll , Rachel A. Kohman
{"title":"Middle-aged females are resistant to LPS-induced learning deficits: Sex comparison","authors":"Lauren G. Singleton , Kelsey F. Thompson , Jordyn Carroll , Rachel A. Kohman","doi":"10.1016/j.neulet.2024.138072","DOIUrl":"10.1016/j.neulet.2024.138072","url":null,"abstract":"<div><div>Preclinical data have repeatedly shown learning and memory disruption following administration of the bacterial endotoxin lipopolysaccharide (LPS). Normal aging is reported to enhance vulnerability to LPS-induced cognitive impairments. However, a limitation is the primary use of male subjects. Recent evidence indicates sex-related differences in vulnerability to LPS-induced cognitive deficits <span><span>[1]</span></span>, <span><span>[2]</span></span>, with young females showing resilience. Whether middle-aged females are susceptible to LPS-induced cognitive impairment is unknown. The current experiment compared associative learning in young and middle-aged male and female C57BL/6J mice following a systemic LPS challenge. While LPS impaired acquisition of the two-way active avoidance conditioning task in adult and middle-aged males, females’ learning was unaffected. The sex difference in LPS-induced cognitive impairments appears unrelated to responsivity to LPS, as males and females mount a comparable sickness-like response. Additionally, relative to males, females produce higher brain levels of interleukin-6 (IL-6) and comparable splenic IL-6 levels following LPS. These data demonstrate that female resilience to LPS-induced learning deficits persists into middle age, whereas males are vulnerable as both young and middle-aged adults. Our findings confirm the importance of considering sex as a biological variable and extend the existing literature by evaluating sex-related responsivity to LPS in middle-aged males and females.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"845 ","pages":"Article 138072"},"PeriodicalIF":2.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cagil Onal Sis , Yagmur Okcay , Kemal Gokhan Ulusoy , Ismail Mert Vural , Oguzhan Yıldız
{"title":"Exploring the antinociceptive effect of taraxasterol in mice: Possible mechanisms","authors":"Cagil Onal Sis , Yagmur Okcay , Kemal Gokhan Ulusoy , Ismail Mert Vural , Oguzhan Yıldız","doi":"10.1016/j.neulet.2024.138075","DOIUrl":"10.1016/j.neulet.2024.138075","url":null,"abstract":"<div><h3>Objectives</h3><div>Taraxasterol is the active ingredient of <em>Taraxacum officinale</em> which has been used in traditional medicine for its several therapeutic effects. This study aims first to evaluate the potential spinal/supraspinal and peripheral/visceral antinociceptive effect of taraxasterol and then to investigate the contribution of GABAergic, opioidergic systems, and K<sub>ATP</sub> channels to its antinociceptive effect.</div></div><div><h3>Methods</h3><div>The antinociceptive activity of taraxasterol (2.5, 5, and 10 mg/kg i.p.) was investigated with hot-plate, tail-immersion, and acetic acid-induced abdominal writhing tests (for supraspinal, spinal, peripheral/visceral pain evaluation, respectively) in BALB/c male mice, and percentage of possible maximum effect (MPE%) values were calculated. Mechanism of action studies were performed by pre-administering bicuculline, naloxone, and glibenclamide.</div></div><div><h3>Results</h3><div>Taraxasterol increased the MPE% values in hot-plate and tail-immersion tests at 2.5, 5, and 10 mg/kg doses (<em>P</em> < 0.001) and decreased the mean number of writhes at 10 mg/kg in the abdominal writhing test (<em>P</em> < 0.05). Naloxone and bicuculline pre-administration reversed the antinociceptive effect of taraxasterol in hot-plate and tail-immersion tests and it had no effect in the abdominal writhing test. Pre-administration of glibenclamide reversed the antinociceptive effect of taraxasterol in all tests.</div></div><div><h3>Conclusion</h3><div>Our study is the first to show the involvement of GABAergic and opioidergic systems in the antinociceptive effect of taraxasterol in supraspinal and spinal pain tests, and K<sub>ATP</sub> channels in tests evaluating supraspinal, spinal, and peripheral pain pathways. Taraxasterol is a potential new herbal medicine that can be used for pain control.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"845 ","pages":"Article 138075"},"PeriodicalIF":2.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matheus F. Batistela , Paloma M. Hernandes , Alana T. Frias , Thelma A. Lovick , Helio Zangrossi Jr
{"title":"Anti-panic effect of fluoxetine during late diestrus in female rats is mediated through GABAergic mechanisms in the dorsal periaqueductal gray","authors":"Matheus F. Batistela , Paloma M. Hernandes , Alana T. Frias , Thelma A. Lovick , Helio Zangrossi Jr","doi":"10.1016/j.neulet.2024.138078","DOIUrl":"10.1016/j.neulet.2024.138078","url":null,"abstract":"<div><div>Panic disorder is more frequent in women than in men. In women, vulnerability to panic is enhanced during the late luteal phase of the menstrual cycle. At this time secretion of progesterone and its neuroactive metabolite allopregnanolone (ALLO), which acts as a positive allosteric modulator of the actions of GABA at GABA<sub>A</sub> receptors, decline sharply. In female rats, responsiveness to a hypoxic panicogenic challenge increases during the late diestrus (LD) phase as ALLO concentration in the brain falls. During LD, short-term treatment with fluoxetine at a low dose (1.75 mg/kg i.p.) blocked panic-related escape behavior in response to hypoxia. At this dose fluoxetine increases brain concentration of ALLO without affecting 5-HT levels, thereby stabilizing brain ALLO concentration. We here report that the panicolytic-like effect of fluoxetine during LD is prevented by microinjection of the GABA<sub>A</sub> receptor antagonist bicuculline (5 pmol) into the dorsal periaqueductal gray (dPAG), a key panic-related area. This result suggests that fluoxetine’s effect is indirectly mediated via a GABAergic mechanism in the dPAG and highlights the important role of changes in GABAergic tone in regulating neuronal excitability in the panic circuitry during the estrous cycle. It also points to the potential for using short-term, low dose fluoxetine as an anti-panic medication in women.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"845 ","pages":"Article 138078"},"PeriodicalIF":2.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mayur B. Kale , Sandip R. Rahangdale , Trupti A. Banarase , Mohd. Shahnavaj Siddiqui , Brijesh G. Taksande , Manish M. Aglawe , Aman B. Upaganlawar , Spandana Rajendra Kopalli , Sushruta Koppula , Milind J. Umekar , Nitu L. Wankhede
{"title":"Agmatine diminishes behavioral and endocrine alterations in a rat model of post-traumatic stress disorder","authors":"Mayur B. Kale , Sandip R. Rahangdale , Trupti A. Banarase , Mohd. Shahnavaj Siddiqui , Brijesh G. Taksande , Manish M. Aglawe , Aman B. Upaganlawar , Spandana Rajendra Kopalli , Sushruta Koppula , Milind J. Umekar , Nitu L. Wankhede","doi":"10.1016/j.neulet.2024.138074","DOIUrl":"10.1016/j.neulet.2024.138074","url":null,"abstract":"<div><div>Post-traumatic stress disorder (PTSD), is a severe anxiety disorder characterized by associative fear conditioning. Single prolonged stress (SPS) is a widely accepted reliable animal model to stimulate PTSD. Agmatine is an endogenous neuromodulator of stress; however, its effect on PTSD remains to be investigated. This study explored the role of agmatine in conditioned fear response (CFR) in PTSD and highlighted the role of imidazoline receptors in the effect of agmatine. Intra-cerebroventricular (icv) surgery was done in order to facilitate drug administration. Animals were subjected to SPS. Agmatine and the involvement of imidazoline receptors (I<sub>1</sub> and I<sub>2</sub>) were assessed for their effect in fear conditioning apparatus. During weeks 1, 2, and 3, in CFR, agmatine (40 µg/rat, icv) showed significantly decreased freezing time whereas other doses of agmatine (10 and 20 µg/rat, icv). Imidazoline (I<sub>1</sub> and I<sub>2</sub>) receptor agonists Moxonidine (25 µg/rat, icv) and 2-BFI, (10 µg/rat, icv) respectively, at their sub-effective doses, with a submaximal dose of agmatine (20 µg/rat, icv) significantly decreased the altered freezing time during weeks 1, 2 and 3 compared to SPS animals. Moreover, the effective dose of agmatine (40 µg/rat, icv) with imidazoline (I<sub>1</sub> and I<sub>2</sub>) receptor antagonists Efaroxan (10 µg/rat, icv) and Idazoxan (4 µg/rat, icv) respectively does not reversed the effect of agmatine on freezing. Agmatine and its combination with I<sub>1</sub> and I<sub>2</sub> agonists, normalized the altered freezing behavior, corticosterone level, organ coefficient of adrenal gland, neuroinflammatory and neurotrophic factor due to SPS during CFR projecting its strong therapeutic effect in SPS induced PTSD.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"845 ","pages":"Article 138074"},"PeriodicalIF":2.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Preventive and therapeutic effects of genistein and daidzein on anxiety-like behaviors in ovariectomized rats","authors":"Sarinee Kalandakanond-Thongsong , Suwaporn Daendee , Sushawadee Tongta , Boonrit Thongsong , Anan Srikiatkhachorn","doi":"10.1016/j.neulet.2024.138073","DOIUrl":"10.1016/j.neulet.2024.138073","url":null,"abstract":"<div><div>Estrogen has demonstrated beneficial effects; however, it can also have unfavorable effects. Phytoestrogens are present in many consumable products and commonly used as supplements. These are of interest as they may have beneficial effects on mood with fewer undesirable effects on reproductive tissues. This study investigated the anxiolytic-like effects of the phytoestrogens genistein and daidzein on ovariectomized (Ovx) rats and their effects on the expression of uterine estrogen receptors (ER) and brain monoamines. In experiment 1, Ovx rats received either vehicle, 17β-estradiol, or 0.25 − 1 mg/kg of genistein or daidzein for 4 weeks before behavioral tests of anxiety. In experiment 2, we assessed the therapeutic effects of genistein and daidzein. The ovariectomies were used to induce anxiety, so the treatments were started 3 weeks post-ovariectomy. The Ovx rats received vehicle, 17β-estradiol, or 0.25 mg/kg of genistein or daidzein daily for 4 weeks before behavioral tests. We found daidzein and genistein comparable to 17β-estradiol in their anxiolytic-like effects. Further, while 17β-estradiol decreased body weight gain, increased uterine weight, and increased the uterine ERα/ERβ ratio, neither genistein nor daidzein had these undesirable effects. The alterations in brain monoamines following genistein or daidzein treatments were somewhat different from those seen after 17β-estradiol treatment. In conclusion, daily daidzein or genistein administration for 4 weeks did not negatively affect body weight, food intake, uterine tissue, uterine ER expressions, or ERα/ERβ ratio but demonstrated anxiolytic-like effects on Ovx rats. We conclude that low-dose (0.25 mg/kg) genistein or daidzein can alleviate anxiety in a female anxious rat model.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"845 ","pages":"Article 138073"},"PeriodicalIF":2.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yun-Kyung Hahn , Sara R. Nass , William D. Marks , Jason J. Paris , Kurt F. Hauser , Pamela E. Knapp
{"title":"Sex related differences in cognitive deficits: Disrupted Arc/Arg3.1 signaling in an HIV model","authors":"Yun-Kyung Hahn , Sara R. Nass , William D. Marks , Jason J. Paris , Kurt F. Hauser , Pamela E. Knapp","doi":"10.1016/j.neulet.2024.138071","DOIUrl":"10.1016/j.neulet.2024.138071","url":null,"abstract":"<div><div>Combined and highly active anti-retroviral therapies (cART) have transitioned HIV into a more chronic disease. Roughly half of people living with HIV (PLWH) still experience neurocognitive disorders, albeit less severely than in the pre-cART era. Sex-related effects on memory/cognition remain understudied, although the percentage of PLWH that are female has increased. We utilized a transgenic mouse model of HIV that conditionally expresses HIV-1 Tat<sub>1-86</sub> in the CNS to examine cognitive behaviors and the expression of biomarkers related to learning and memory in both sexes. Tat+ males exhibited deficits in spatial learning/memory and object recognition, while Tat+ females showed enhanced fear memory. We investigated the involvement of activity-regulated cytoskeleton-associated protein (Arc), which is induced by novel experience related to learning/memory. We observed hippocampal Arc induction following foot shock in Tat+ females but not Tat+ males. Hippocampal levels of Arc, amyloid β (Aβ) monomers/oligomers and pCREB were altered in a sex-specific manner. CREB activity, which is highly associated with Arc induction, was reduced only in Tat+ males. Tat exposure also decreased Arc expression in cultured human neurons. Thus, HIV-1 Tat effects on CREB/Arc signaling may differ between sexes, contributing to differences in cognitive deficits observed here and in PLWH.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"845 ","pages":"Article 138071"},"PeriodicalIF":2.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Akira Mitani, Tomoko Shimizu, Jun Terai, Koji Maeda, Kohei Suzuki, Kazumi Kioka
{"title":"Neuroplasticity in the motor cortex following the achievement of sufficient motor learning","authors":"Akira Mitani, Tomoko Shimizu, Jun Terai, Koji Maeda, Kohei Suzuki, Kazumi Kioka","doi":"10.1016/j.neulet.2025.138117","DOIUrl":"10.1016/j.neulet.2025.138117","url":null,"abstract":"<div><div>Skilled motor training causes the cortical representation of the trained body parts to expand into regions of the motor cortex related to other body parts. However, the effect of neuroplastic changes on the neurons originally existing within the expanded area is not well understood. In this study, the extent of the neuroplastic changes after achieving sufficient motor learning and the impact of the expansion on the neurons related to movements of other body parts were investigated. Rats were trained to perform a single-pellet retrieval reaching task, and intracortical microstimulation in the motor cortex was used to assess neuroplastic changes. After 54 to 73 days of training, the trained rats achieved sufficient motor learning. In the motor cortex, the occurrence rate of evoked wrist movements increased to approximately double that of the control group in the expanded area. This finding suggests that the extent of neuroplastic changes in the occurrence rate of evoked movements in the motor cortex achieved through sufficient motor learning is approximately double. Additionally, stimulation in the expanded area predominantly evoked vibrissae movements in the control group; however, the occurrence rate and threshold of evoked vibrissae movements were not significantly changed in the expanded areas in the trained group. This observation may suggest that the expansion of cortical areas corresponding to the trained body parts does not disrupt the original function of movements of other parts in the expanded area.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"849 ","pages":"Article 138117"},"PeriodicalIF":2.5,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alberto Avila-Luna , Rodrigo Cruz-Castro , Antonio Verduzco-Mendoza , Adriana Olmos-Hernández , Arturo Gálvez-Rosas , Alfonso Alfaro-Rodríguez , José-Antonio Arias-Montaño , Antonio Bueno-Nava
{"title":"Traumatic brain injury, alone or with striatal hemorrhage-like extension, transiently decreases GABA and glutamate levels along motor deficits in the rat striatum: an in vivo study","authors":"Alberto Avila-Luna , Rodrigo Cruz-Castro , Antonio Verduzco-Mendoza , Adriana Olmos-Hernández , Arturo Gálvez-Rosas , Alfonso Alfaro-Rodríguez , José-Antonio Arias-Montaño , Antonio Bueno-Nava","doi":"10.1016/j.neulet.2024.138070","DOIUrl":"10.1016/j.neulet.2024.138070","url":null,"abstract":"<div><div>The cerebral cortex is connected to the striatum via the axons of the pyramidal glutamatergic neurons, and this pathway is intimately involved in motor function. In the striatum, glutamatergic afferents initiate the activity of GABAergic medium spiny neurons. This study addressed whether traumatic brain injury (TBI) affects GABA and glutamate extracellular levels in the dorsal striatum as an indicator of effects on the cortico-striatal pathway, in rats with motor deficits and recovered animals. Animals were assigned to a sham group, a TBI-alone group, and a TBI + striatal injury group (local injection of a FeCl<sub>2</sub> solution to mimic hemorrhagic lesion). In the TBI-alone and TBI + striatal injury groups, motor deficits were accompanied by decreased extracellular GABA and glutamate levels in the striatum at 3 days post-injury. The TBI + striatal injury group showed higher motor deficits, which lasted 7 days longer, and GABA levels were significantly different compared to the TBI alone group. At 18 days post-injury, in recovered rats from the TBI-alone group GABA and glutamate levels returned to control levels. Alterations in extracellular GABA and glutamate levels indicate damage to the cortico-striatal pathway, underscoring the importance of studying this pathway for treatment and recovery after TBI.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"845 ","pages":"Article 138070"},"PeriodicalIF":2.5,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Panagiotis Kerezoudis , Michael A Jensen , Harvey Huang , Jeffrey G. Ojemann , Bryan T. Klassen , Nuri F. Ince , Dora Hermes , Kai J Miller
{"title":"Spatial and spectral changes in cortical surface potentials during pinching versus thumb and index finger flexion","authors":"Panagiotis Kerezoudis , Michael A Jensen , Harvey Huang , Jeffrey G. Ojemann , Bryan T. Klassen , Nuri F. Ince , Dora Hermes , Kai J Miller","doi":"10.1016/j.neulet.2024.138062","DOIUrl":"10.1016/j.neulet.2024.138062","url":null,"abstract":"<div><div>Electrocorticographic (ECoG) signals provide high-fidelity representations of sensorimotor cortex activation during contralateral hand movements. Understanding the relationship between independent and coordinated finger movements along with their corresponding ECoG signals is crucial for precise brain mapping and neural prosthetic development. We analyzed subdural ECoG signals from three adult epilepsy patients with subdural electrode arrays implanted for seizure foci identification. Patients performed a cue-based task consisting of thumb flexion, index finger flexion or a pinching movement of both fingers together. Broadband power changes were estimated using principal component analysis of the power spectrum. All patients showed significant increases in broadband power during each movement compared to rest. We created topological maps for each movement type on brain renderings and quantified spatial overlap between movement types using a resampling metric. Pinching exhibited the highest spatial overlap with index flexion, followed by superimposed index and thumb flexion, with the least overlap observed for thumb flexion alone. This analysis provides practical insights into the complex overlap of finger representations in the motor cortex during various movement types and may help guide more nuanced approaches to brain-computer interfaces and neural prosthetics.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"845 ","pages":"Article 138062"},"PeriodicalIF":2.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Activation of mouse skin mast cells and cutaneous afferent C-fiber subtypes by bee venom","authors":"Danica Jurcakova , Fei Ru , Renata Pecova , Bradley J Undem","doi":"10.1016/j.neulet.2024.138061","DOIUrl":"10.1016/j.neulet.2024.138061","url":null,"abstract":"<div><div>In mammals, many Hymenopteran stings are characterized by pain, redness, and swelling − three manifestations consistent with nociceptive nerve fiber activation. The effect of a Western honeybee <em>(Apis mellifera)</em> venom on the activation of sensory C-fibers in mouse skin was studied using an innervated isolated mouse skin preparation that allows for intra-arterial delivery of chemicals to the nerve terminals in the skin. Our data show that honeybee venom stimulated mouse cutaneous nociceptive-like C-fibers, with an intensity (action potential discharge frequency) similar to that seen with a maximally-effective concentration of capsaicin. The venom had a stronger effect on chloroquine-sensitive C-fibers compared to chloroquine-insensitive C-fibers, an effect that was recapitulated with a wasp <em>(Vespula</em> spp.<em>)</em> venom. Blocking TRPV1 and TRPA1 channels did not influence the honeybee venom-induced C-fiber activation. The effect of the venoms on chloroquine-sensitive and −insensitive subpopulation of C-fiber terminals was mimicked by melittin but not apamin; two of peptide venom components. Chloroquine-sensitive C-fibers are stimulated as a consequence of mast cell activation. Melittin degranulated mast cells in mouse skin by a non-IgE and non-MrgprB2 mechanism, and this may explain the stronger activation of the chloroquine-sensitive C-fibers.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"845 ","pages":"Article 138061"},"PeriodicalIF":2.5,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}