Chih-Ju Chou , Chi-Wai Cheung , Chien-Ching Lee , Sheng-Nan Wu , Rasa Liutkeviciene , Vita Rovite , Edmund Cheung So
{"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 , Chi-Wai Cheung , Chien-Ching Lee , Sheng-Nan Wu , Rasa Liutkeviciene , Vita Rovite , 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 (GH<sub>3</sub>) cells, was investigated. AS2034178 suppressed transient (<em>I</em><sub>Na(T)</sub>) and late (<em>I</em><sub>Na(L)</sub>) components of voltage-gated Na<sup>+</sup> current (<em>I</em><sub>Na</sub>) with IC<sub>50</sub> 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><sub>Na(T)</sub> leftward. AS2034178 also blocked persistent Na<sup>+</sup> current (<em>I</em><sub>Na(P)</sub>) activated by long-lasting ramp voltages, and subsequent application of deltamethrin or tefluthrin attenuated its suppression. The compound prolonged recovery of <em>I</em><sub>Na(P)</sub> inactivation, shifted its inactivation curve, and shortened time constant for <em>I</em><sub>N(P)</sub> decay. Additionally, AS2034178 suppressed delayed-rectifier K<sup>+</sup> current (<em>I</em><sub>K(DR)</sub>) with a dissociation constant of 6.23 µM. Docking studies suggested AS2034178′s ability to interact with amino acid residues in hNa<sub>V</sub>1.7 channels.(supplementary data). AS2034178′s effects on ionic currents (<em>I</em><sub>Na</sub> and <em>I</em><sub>K(DR)</sub>) 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}
Barbora Bodorova , Denisa Mihalj , Tomas Havranek , Zuzana Bacova , Jan Bakos
{"title":"VIP and PACAP enhance hippocampal neuronal cell proliferation especially GFAP-positive astrocytes, while PACAP inhibits neurite outgrowth","authors":"Barbora Bodorova , Denisa Mihalj , Tomas Havranek , Zuzana Bacova , 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}
Emma Balog , Gyula Jenei , Anikó Magyariné Berkó , Bálint Lőrinczi , István Szatmári , László Vécsei , József Toldi , Zsolt Kis
{"title":"Age-dependent changes in NMDA-induced excitotoxicity and neuromodulatory effects of kynurenic acid and its analogue in mouse brain slices","authors":"Emma Balog , Gyula Jenei , Anikó Magyariné Berkó , Bálint Lőrinczi , István Szatmári , László Vécsei , József Toldi , 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}
Kazushige Yokoyama , Joel Mukkatt , Nicole Mathewson , Marc D. Fazzolari , Victoria D. Hackert , Mohamed M. Ali , Abel C. Monichan , Agnes J. Wilson , Benjamin C. Durisile , Lorenz S. Neuwirth
{"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 , Joel Mukkatt , Nicole Mathewson , Marc D. Fazzolari , Victoria D. Hackert , Mohamed M. Ali , Abel C. Monichan , Agnes J. Wilson , Benjamin C. Durisile , 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<sup>−1</sup> – 1250 cm<sup>−1</sup> 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 , İlker Güleç , Aslıhan Şengelen , Feyza Karagöz-Güzey , Burak Eren , Azmi Tufan , Tevhide Bilgen Özcan , 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}
Jaime Fabillar Jr. , Lutfi Putra Perdana , Swarnalakshmi Raman , Junhel Dalanon , Masamitsu Oshima , Otto Baba , Yoshizo Matsuka
{"title":"Bilateral transport of neuronal tracer after unilateral administration: Investigation of potential peripheral mechanism","authors":"Jaime Fabillar Jr. , Lutfi Putra Perdana , Swarnalakshmi Raman , Junhel Dalanon , Masamitsu Oshima , Otto Baba , 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}
Abigail M. Schwarz , Caleb A. Seekins , Omar El-Sissi , John M. Streicher
{"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 , Caleb A. Seekins , Omar El-Sissi , 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<sub>2a</sub> Receptors (A<sub>2a</sub>R) 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<sub>2a</sub>R antagonist istradefylline blocked the pain-relieving effects of all three terpene blends, suggesting that the terpene blends act on A<sub>2a</sub>R 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}
{"title":"Comparison of G6PD activity with a modified hormonal environment during the critical period of hypothalamic sexual differentiation in Sprague Dawley rats","authors":"Chávez García Ricardo , Ortega Camarillo Clara , Contreras Ramos Alejandra , Díaz Rosas Guadalupe , Avalos Rodríguez Alejandro , J.J. Pérez-Rivero , Vergara Onofre Marcela","doi":"10.1016/j.neulet.2025.138206","DOIUrl":"10.1016/j.neulet.2025.138206","url":null,"abstract":"<div><div>The neuronal cells that make up the dysmorphic nuclei located in the hypothalamus of both female and male mammals are susceptible to the hormonal environment in which individuals find themselves during the critical period of cerebral sexual differentiation. Thus, endogenous and exogenous steroids influence the remodeling process of hypothalamic structures using apoptosis or cell proliferation processes, which are implicit in the mechanism of cerebral sexual differentiation. In this study, the enzymatic kinetics and the relative expression of G6PD mRNA and the concentration of GSH were compared to verify whether the redox state modified by the exogenous administration of synthetic hormones, such as tamoxifen in males and testosterone propionate in females, influences the apoptosis process (Bax and Bcl-2) within the mechanism of hypothalamic sexual differentiation in Sprague Dawley rats. It was observed that the G6PD activity for the F-CTR group was higher at 1 and 3 h compared to the M-TAM organisms. The F-TP group registered more significant values at 3 h compared to the M-CTR group. For the GSH concentrations, the F-CTR and M-CTR groups exhibited the highest concentrations at 12, 24, and 48 h. In the experimental groups, the GSH concentrations remained at decreased levels from the first hour to 48 h with a slight increase at 3600 h in the F-TP. In the case of the M-TAM, the GSH levels rose from hour 3 to hour 12.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"855 ","pages":"Article 138206"},"PeriodicalIF":2.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692784","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}
Neil P.M. Todd , Sendhil Govender , Daniel Hochstrasser , Peter E. Keller , James G. Colebatch
{"title":"Distinct movement related changes in EEG and ECeG power during finger and foot movement","authors":"Neil P.M. Todd , Sendhil Govender , Daniel Hochstrasser , Peter E. Keller , James G. Colebatch","doi":"10.1016/j.neulet.2025.138207","DOIUrl":"10.1016/j.neulet.2025.138207","url":null,"abstract":"<div><div>Voluntary movement is known to be associated with cerebrally generated movement-related slow potentials and parallel changes in spectral power. The cerebellar and cerebral cortices are powerfully connected via reciprocal, crossed projections which mediate their coordination in motor, as well as cognitive and affective processes. The cerebellum participates in movement and the question remains as to the nature of movement related changes in power if any which might occur over the cerebellum. In a sample of six healthy adult subjects, we recorded EEG and the electro-cerebellogram (ECeG) with a 10 % cerebellar extension montage during voluntary left and right index finger and foot movements. EMG was recorded from finger extensors and flexors and from the tibialis anterior and soleus muscles and was used to generate triggers for movement related averaging (−2000 to + 2000 ms). Wavelet power was computed over the 4 s epoch for each electrode. For statistical analysis, cerebral and cerebellar grids centred around Cz and SIz were investigated, using both average and linked-ear references. Statistically significant movement related changes were observed in both cerebral and cerebellar power, most significantly in the high delta band (1.5 to 3 Hz), for both montages. In contrast to Cz where power increased premovement, power was reduced over the cerebellum. High-frequency pause-bursting was also observed in the ECeG around the time of movement. Our results indicate that recordings over the cerebellum show distinct changes from those over Cz and in particular show a fall in power during the premovement period.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"853 ","pages":"Article 138207"},"PeriodicalIF":2.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674246","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}
Li Zhang , Shuai Zhou , Yuen Fen Tan , Quan Fu Gan , Teoh Hoon Koon , Zhiqiang Wang , Shiqing Zhao , Yixuan Chen , Yi Sun , Pooi Pooi Leong
{"title":"Collateral projections from the lateral parabrachial nucleus to the bed nucleus of the stria terminalis and the central amygdala in mice","authors":"Li Zhang , Shuai Zhou , Yuen Fen Tan , Quan Fu Gan , Teoh Hoon Koon , Zhiqiang Wang , Shiqing Zhao , Yixuan Chen , Yi Sun , Pooi Pooi Leong","doi":"10.1016/j.neulet.2025.138204","DOIUrl":"10.1016/j.neulet.2025.138204","url":null,"abstract":"<div><h3>Background</h3><div>The lateral parabrachial nucleus (LPBn) serves a critical hub for processing and transmitting pain signals. It has two main efferent pathways, the LPBn-CeA and LPBn-BNST, which are crucial for pain regulation and the management of negative emotions.</div></div><div><h3>Methods</h3><div>In our study, we investigated the projections from the LPBn by performing stereotaxic injections of AAV2/2Retro-hSyn-EGFP (abbreviated as EGFP) into the bed nucleus of the stria terminalis (BNST) and AAV2/2Retro-hSyn-tdTomato (abbreviated as tdTomato) into the central amygdala (CeA) in mice. The animals subsequently underwent spared nerve injury (SNI) surgery on the contralateral side to the AAV injections. To examine the expression of calcitonin gene-related peptide (CGRP) and c-Fos, we conducted immunofluorescent histochemistry.</div></div><div><h3>Results</h3><div>Our results indicated that approximately 26 % of the LPBn neurons retrogradely labeled with either EGFP or tdTomato were dual-labeled with both markers. Moreover, a significant majority (85.49 %) of these double-labeled neurons were CGRP positive (CGRP<sup>+</sup>). In mice subjected to SNI, nearly all of these neurons (93.25 %) were c-Fos positive (c-Fos<sup>+</sup>), indicating that they were activated.</div></div><div><h3>Conclusion</h3><div>These findings suggest that a subset of CGRP<sup>+</sup> neurons in the LPBn projects to both the BNST and CeA via axon collaterals. Notably, under SNI conditions, these neurons may play a critical role in the transmission of chronic pain.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"853 ","pages":"Article 138204"},"PeriodicalIF":2.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670463","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}