Neuroscience Letters最新文献

{"title":"Brain AMPK signaling improves intestinal barrier function through brain orexin and the vagal pathway in rats","authors":"Takuya Funayama ,&nbsp;Tsukasa Nozu ,&nbsp;Masatomo Ishioh ,&nbsp;Chihiro Sumi ,&nbsp;Takeshi Saito ,&nbsp;Mayumi Hatayama ,&nbsp;Masayo Yamamoto ,&nbsp;Motohiro Shindo ,&nbsp;Shuichiro Takahashi ,&nbsp;Toshikatsu Okumura","doi":"10.1016/j.neulet.2025.138208","DOIUrl":"10.1016/j.neulet.2025.138208","url":null,"abstract":"<div><div>Leaky gut, an increased intestinal permeability, has been described in many diseases. We have recently demonstrated that neuropeptides such as orexin in the brain improved leaky gut, suggesting that the brain is involved in maintaining intestinal barrier function. It has been suggested that AMPK in the hypothalamus play a role in food intake. Because the hypothalamus is involved in the regulation of not only feeding behavior but also gut function, the present study was performed to clarify a hypothesis that AMPK in the brain regulate gut barrier function. Colonic permeability was determined by quantifying the absorbed Evans blue within the colonic tissue in rats. Intracisternal AICAR, an AMPK activator, could reduce LPS-induced colonic hyperpermeability while peripherally administered AICAR failed to change it. The improvement of colonic hyperpermeability by intracisternal AICAR was blocked by intracisternal but not subcutaneous compound C, AMPK inhibitor, atropine or vagotomy. The improvement of colonic hyperpermeability by intracisternal AICAR was blocked by intracisternal orexin receptor antagonist but not oxytocin or GLP-1 receptor antagonist. Intracisternal compound C prevented brain oxytocin or GLP-1 but not orexin-induced improvement of colonic hyperpermeability. These results suggest that activation of brain AMPK is capable of reducing colonic hyperpermeability through brain orexin signaling and the vagus nerve. In addition, endogenous AMPK in the brain may mediate the oxytocin or GLP-induced improvement of colonic hyperpermeability. We would suggest that improvement of leaky gut by activation of brain AMPK may play a role in leaky gut-related diseases.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"854 ","pages":"Article 138208"},"PeriodicalIF":2.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739158","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":"EEG alpha power during creative ideation of graphic symbols","authors":"Evelyn Cordero ,&nbsp;Eugenio Rodríguez ,&nbsp;Paulo Barraza","doi":"10.1016/j.neulet.2025.138221","DOIUrl":"10.1016/j.neulet.2025.138221","url":null,"abstract":"<div><div>Graphic symbolic creation—transforming abstract concepts into visual forms—is a cognitively complex and uniquely human skill. Neurophysiological evidence suggests that oscillatory alpha activity is correlated with visual-figurative creative thinking. However, whether alpha oscillations play a functional role in generating graphic symbols remains unclear. To address this issue, we compared the EEG alpha power of 40 healthy adults while ideating creative and conventional graphic symbols representing an abstract concept’s meaning (e.g., the word ’peace’). Our results revealed that the ideation of graphic symbols elicited alpha synchronization, with higher levels in the conventional compared to the creative condition, mainly over frontal-central, frontal-temporal, parietal-occipital, and occipital regions. Furthermore, we observed greater alpha synchronization in the right hemisphere than in the left across both conditions, particularly between temporal, central-parietal, and parietal electrodes. This asymmetry extended to central electrodes in the creative condition, while in the conventional condition, it was more pronounced over parietal-occipital regions. Finally, we also found that frontal and occipital alpha synchronization during the creative ideation phase predicted the subsequent originality scores of the graphic symbols produced. Together, these findings enhance our understanding of the dynamics of oscillatory alpha activity during graphic symbol creation, shedding light on how the interaction between inhibitory top-down control mechanisms and cognitive flexibility processes facilitates the transformation of abstract concepts into visual forms. These findings provide new insights into the neural processes underlying this uniquely human ability.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"855 ","pages":"Article 138221"},"PeriodicalIF":2.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780606","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":"MiR-30b-5p alleviates trigeminal neuralgia induced by chronic constriction injury of the infraorbital nerve by regulating the voltage-gated sodium channel Nav1.3 in rats","authors":"Tingting Hu ,&nbsp;Mengci Shao ,&nbsp;Jiajia Liu ,&nbsp;Xiaorong Yan ,&nbsp;Liecheng Wang ,&nbsp;Yuanyin Wang ,&nbsp;Wenhua Xu","doi":"10.1016/j.neulet.2025.138223","DOIUrl":"10.1016/j.neulet.2025.138223","url":null,"abstract":"<div><div>Nav1.3 is a tetrodotoxin-sensitive voltage-gated sodium channel isoform encoded by SCN3A, the abnormal expression of which plays a crucial role in the generation of ectopic discharge, as well as being associated with allodynia and hyperalgesia. Using bioinformatics analysis, we showed that miR-30b-5p directly targets SCN3A. We aimed to explore whether miR-30b-5p can participate in trigeminal neuralgia (TN) in rats by regulating the expression of Nav1.3. The rat TN model was constructed through infraorbital nerve-chronic constriction injury (ION-CCI), which was verified by measuring the change in mechanical threshold and the expression of activating transcription factor 3 (a marker of nerve damage) in the trigeminal ganglia (TG). The expression of miR-30b-5p in postoperative TG was downregulated, whereas that of Nav1.3 was upregulated in rats subjected to ION-CCI. Overexpression of miR-30b-5p repressed the expression of Nav1.3 in TG and alleviated ION-CCI-induced TN. MiR-30b-5p targets to regulate the expression of SCN3A, thereby reducing or aggravating TN. Therefore, miR-30b-5p may be a novel therapeutic target for neuropathic pain.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"855 ","pages":"Article 138223"},"PeriodicalIF":2.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence for effective suppression of INa and IK(DR) by AS2034178 (bis{2-[(4-{(4′-(2-hydroxyethoxy)-2′-methyl[1,1′-biphenyl]-3-yl)methoxy}phenyl]methyl]-3,5-dioxo-1,2,4-oxadiazolidin-4-ide} tetrahydrate), an agonist of free fatty acid receptor","authors":"Chih-Ju Chou ,&nbsp;Chi-Wai Cheung ,&nbsp;Chien-Ching Lee ,&nbsp;Sheng-Nan Wu ,&nbsp;Rasa Liutkeviciene ,&nbsp;Vita Rovite ,&nbsp;Edmund Cheung So","doi":"10.1016/j.neulet.2025.138222","DOIUrl":"10.1016/j.neulet.2025.138222","url":null,"abstract":"<div><div>AS2034178, an agonist of free fatty acid receptor-1 or G protein-coupled receptor 40, enhances pancreatic β-cell function. Its impact on ionic currents in excitable cells, particularly pituitary tumor (GH₃) cells, was investigated. AS2034178 suppressed transient (<em>I</em>_Na(T)) and late (<em>I</em>_Na(L)) components of voltage-gated Na⁺ current (<em>I</em>_Na) with IC₅₀ values of 29.8 and 5.3 µM, respectively. It did not alter current–voltage relationship but shifted steady-state inactivation curve of <em>I</em>_Na(T) leftward. AS2034178 also blocked persistent Na⁺ current (<em>I</em>_Na(P)) activated by long-lasting ramp voltages, and subsequent application of deltamethrin or tefluthrin attenuated its suppression. The compound prolonged recovery of <em>I</em>_Na(P) inactivation, shifted its inactivation curve, and shortened time constant for <em>I</em>_N(P) decay. Additionally, AS2034178 suppressed delayed-rectifier K⁺ current (<em>I</em>_K(DR)) with a dissociation constant of 6.23 µM. Docking studies suggested AS2034178′s ability to interact with amino acid residues in hNa_V1.7 channels.(supplementary data). AS2034178′s effects on ionic currents (<em>I</em>_Na and <em>I</em>_K(DR)) contribute to its mechanisms of action in culture or <em>in vivo</em>.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"855 ","pages":"Article 138222"},"PeriodicalIF":2.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VIP and PACAP enhance hippocampal neuronal cell proliferation especially GFAP-positive astrocytes, while PACAP inhibits neurite outgrowth","authors":"Barbora Bodorova ,&nbsp;Denisa Mihalj ,&nbsp;Tomas Havranek ,&nbsp;Zuzana Bacova ,&nbsp;Jan Bakos","doi":"10.1016/j.neulet.2025.138230","DOIUrl":"10.1016/j.neulet.2025.138230","url":null,"abstract":"<div><div>Despite their known roles in regulating food intake, appetite, satiety, and social behavior, the roles of vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) in hippocampal neuronal cell development remain unclear. Therefore, the aim was to evaluate the effect of VIP and PACAP on 1) the proliferation of a hippocampal cell line, 2) the number of neurons and astrocytes in primary hippocampal cell culture, and 3) the morphology of primary hippocampal neurons. It was found that both VIP (100 nM) and PACAP (100 nM) stimulated the proliferation of E2 hippocampal cells over a 72-hour period. A significant increase in the number of NeuN-positive primary hippocampal neurons was observed following VIP incubation on day in vitro (DIV) 9. An increase in GFAP-positive cells following PACAP incubation was observed from DIV3 compared to DIV5, DIV7, and DIV9. PACAP significantly inhibited the growth of short neurites in primary hippocampal neurons. In conclusion, this study demonstrates that both neuropeptides VIP and PACAP influence the proliferation and growth of hippocampal neuronal cells, with PACAP having a more pronounced effect on astrocyte numbers and reducing neurite branching. These findings emphasize the role of VIP and PACAP in the hippocampus during early brain development.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"855 ","pages":"Article 138230"},"PeriodicalIF":2.5,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753752","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":"Age-dependent changes in NMDA-induced excitotoxicity and neuromodulatory effects of kynurenic acid and its analogue in mouse brain slices","authors":"Emma Balog ,&nbsp;Gyula Jenei ,&nbsp;Anikó Magyariné Berkó ,&nbsp;Bálint Lőrinczi ,&nbsp;István Szatmári ,&nbsp;László Vécsei ,&nbsp;József Toldi ,&nbsp;Zsolt Kis","doi":"10.1016/j.neulet.2025.138220","DOIUrl":"10.1016/j.neulet.2025.138220","url":null,"abstract":"<div><div>Kynurenic acid (KYNA) is one of the main neuroprotective substances of the kynurenine pathway. KYNA plays an important role in various neurodegenerative and psychiatric diseases. Although KYNA has been shown to have neuroprotective effects, it cannot be used as a peripherally administered drug due to its poor ability to cross the blood–brain barrier. To address this limitation, chemically modified KYNA analogues are being developed: SZR72 is one such analogue and has been shown to be protective in various animal models. Glutamate-induced excitotoxicity is a key factor in many neurodegenerative diseases. Therefore, we used the N-methyl-D-aspartate (NMDA)-induced excitotoxicity model to investigate the neuromodulatory agents.</div><div>Using acute hippocampal slices from mouse brains, we investigated the potential neuroprotective effect of KYNA and its analogue, SZR72 on NMDA-induced excitotoxicity across different age groups of mice. The degree of tissue damage was assessed using biochemical and histological methods.</div><div>In young animals (1- and 4-week-old), NMDA treatment caused no significant changes, and the cells were found to be resistant. However, in older animals (8-week-old and 1-year-old), NMDA caused significant damage in cells and tissue structure, which was reduced by KYNA and SZR72 treatment.</div><div>To our knowledge, this is the first study to compare the neuroprotective effects of KYNA and SZR72 in animals of different ages using an <em>in vitro</em> NMDA excitotoxicity model.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"854 ","pages":"Article 138220"},"PeriodicalIF":2.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726045","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":"Oligomer sensitive in-situ detection and characterization of gold colloid aggregate formations observed within the hippocampus of the Alzheimer’s disease rat","authors":"Kazushige Yokoyama ,&nbsp;Joel Mukkatt ,&nbsp;Nicole Mathewson ,&nbsp;Marc D. Fazzolari ,&nbsp;Victoria D. Hackert ,&nbsp;Mohamed M. Ali ,&nbsp;Abel C. Monichan ,&nbsp;Agnes J. Wilson ,&nbsp;Benjamin C. Durisile ,&nbsp;Lorenz S. Neuwirth","doi":"10.1016/j.neulet.2025.138218","DOIUrl":"10.1016/j.neulet.2025.138218","url":null,"abstract":"<div><div>In order to better understand the dynamics governing the formation of pathological oligomers leading to Alzheimer’s disease (AD) in a rat model the present study examined the protein aggregates accumulating on gold colloids in the hippocampus. Sections of the hippocampus of the Long Evans Cohen’s AD(+) rat model were mixed with gold colloids and the resulting aggregates were examined by Surface Enhanced Raman Scattering (SERS) imaging. Compared to AD(–) rat tissues, the AD(+) rat hippocampal tissues produced a larger sized gold colloid aggregates. The SERS spectrum of each hippocampal section exhibited similar spectral patterns in the Amide I, II, and III band regions, but showed distinct spectral patterns in the region between 300 cm⁻¹ – 1250 cm⁻¹ in AD(+) rat tissues, respectively. Amyloid fibrils with a β-sheet conformation were previously reported to form gold colloid aggregates in mouse and human AD brain tissues. The gold colloid aggregates in the AD (+) rat hippocampal brain sections showed distinct morphological traits compared to those observed in AD(–) rats. This suggests that there is a spatial distribution of oligomer concentration in the hippocampus, which induces fibril formation to disrupt neuronal networks within the hippocampus and between other parts of the brain.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"855 ","pages":"Article 138218"},"PeriodicalIF":2.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730915","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":"Aloperine treatment attenuates acute spinal cord injury by reducing oxidative, inflammatory, and apoptotic responses via PI3K/AKT/NF-κB signaling in a rat contusion model","authors":"Erhamit Okutan ,&nbsp;İlker Güleç ,&nbsp;Aslıhan Şengelen ,&nbsp;Feyza Karagöz-Güzey ,&nbsp;Burak Eren ,&nbsp;Azmi Tufan ,&nbsp;Tevhide Bilgen Özcan ,&nbsp;Evren Önay-Uçar","doi":"10.1016/j.neulet.2025.138203","DOIUrl":"10.1016/j.neulet.2025.138203","url":null,"abstract":"<div><div>Spinal cord injury (SCI) is a severe condition that can result in nerve damage, impaired motor or sensory function, and ultimately a high mortality rate for injured individuals. High oxidative and inflammatory responses are closely linked to poor prognosis and can influence the recovery of neurological functions. Therefore, overcoming these processes early is a valuable therapy approach for SCI. Aloperine (ALO) is a quinolizidine-type alkaloid with numerous pharmacological activities, including antioxidant, anti-inflammatory, and neuroprotective effects. However, the role of ALO in SCI recovery remains unclear. Herein, we investigated its therapeutic impact on a contusion model of moderate SCI. ALO (100 mg/kg/day) was intraperitoneally administered to adult Sprague-Dawley rats for a week following surgery/SCI. Basso-Beattie-Bresnahan locomotor score was used to assess neural function after post-SCI (day-1/4/7), showing that ALO modestly improved hind-limb locomotor recovery. HE-staining showed that ALO attenuated the increased tissue sparseness and liquefactive necrosis due to the contusion injury. ALO treatments reduced the injury-induced apoptosis (Bax/Bcl-2, cleaved-caspase3), oxidative (4HNE, MDA), and inflammatory (NF-κB, TNF-α) responses, and increased antioxidant enzymes SOD1 and GPx1 levels. The network pharmacology and immunoblot analyses revealed that the molecular targets of ALO and SCI include the PI3K/AKT pathway. Our findings, for the first time, clearly demonstrated that a natural compound, aloperine, has a neuroprotective effect on SCI by reducing apoptosis, inducing the antioxidant defense system, and modulating PI3K/AKT and NF-κB signaling. These results suggest that aloperine administration might improve the total antioxidant status and significantly promote functional recovery following traumatic SCI.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"854 ","pages":"Article 138203"},"PeriodicalIF":2.5,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143704890","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":"Bilateral transport of neuronal tracer after unilateral administration: Investigation of potential peripheral mechanism","authors":"Jaime Fabillar Jr. ,&nbsp;Lutfi Putra Perdana ,&nbsp;Swarnalakshmi Raman ,&nbsp;Junhel Dalanon ,&nbsp;Masamitsu Oshima ,&nbsp;Otto Baba ,&nbsp;Yoshizo Matsuka","doi":"10.1016/j.neulet.2025.138219","DOIUrl":"10.1016/j.neulet.2025.138219","url":null,"abstract":"<div><div>Previous studies have shown pain attenuation after the administration of botulinum neurotoxin type A into the whisker pad contralateral to the nerve injury. It further showed localization in the neurons of the bilateral trigeminal ganglia, indicating a possible connection between the trigeminal nerves. Thus, this study aimed to investigate the potential link between the right and left trigeminal ganglia, considering their anatomical proximity and the possible neural interactions between these structures. The fluorogold (FG) neuronal tracer was localized in the neurons of both the right and left trigeminal ganglia (TG) after unilateral injection into the whisker pad. In contrast, there was a substantial decrease in FG localization in the contralateral ganglion following colchicine (CCh) administration or after midline incision surgery. Moreover, FG injected directly into the trigeminal ganglion was exclusively localized on the ipsilateral side. Additionally, systemic administration of FG revealed its localization not only within the bilateral TG neurons but also in the bilateral dorsal root ganglia (DRG) neurons, mirroring the findings following whisker pad injection. These findings suggest that bilateral transport of fluorogold occurs at the peripheral level, possibly through its diffusion from the injection site to the contralateral whisker pad and/or nerve axonal crossover through the midline. Further studies are required to clarify the specific peripheral pathways and explore the bilateral nerve connections.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"854 ","pages":"Article 138219"},"PeriodicalIF":2.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692783","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":"Terpene blends from Cannabis sativa are cannabimimetic and antinociceptive in a mouse chronic neuropathic pain model via activation of adenosine A2a receptors","authors":"Abigail M. Schwarz ,&nbsp;Caleb A. Seekins ,&nbsp;Omar El-Sissi ,&nbsp;John M. Streicher","doi":"10.1016/j.neulet.2025.138205","DOIUrl":"10.1016/j.neulet.2025.138205","url":null,"abstract":"<div><div>An increase in the use of medicinal <em>Cannabis</em> for pain management has spurred research into the understudied bioactive compounds in <em>Cannabis</em>, such as terpenes. In our previous work, we showed that isolated and purified terpenes were cannabimimetic and also relieved chemotherapy-induced peripheral neuropathy (CIPN) pain via activation of Adenosine A_2a Receptors (A_2aR) in the spinal cord. However, terpenes are most often consumed by the public as complex extracts and mixtures, not purified individual terpenes, and whether this cannabimimetic and antinociceptive activity holds true in terpene extracts and blends is not clear. In this study, we thus extracted terpene blends from three distinct <em>Cannabis</em> chemovars and assessed these blends in male and female CD-1 mice for their cannabimimetic activity in the tetrad assay and pain-relieving properties in a CIPN model. Each terpene blend was unique in the relative amounts of different terpenes extracted. Though each blend was unique, each similarly elicited cannabimimetic behaviors of catalepsy, hyperlocomotion, and hypothermia, without tail flick analgesia. All three terpene blends effectively relieved CIPN, though the antinociception was more robust in male than in female mice. This antinociception was recapitulated by purified Myrcene but not D-Limonene. The A_2aR antagonist istradefylline blocked the pain-relieving effects of all three terpene blends, suggesting that the terpene blends act on A_2aR to relieve CIPN pain. Together, these findings suggest that terpene blends have similar pharmacological effects as purified single terpenes, and that observations made with single terpenes may be applicable to the complex terpene mixtures commonly consumed by the public.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"854 ","pages":"Article 138205"},"PeriodicalIF":2.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692787","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}