Pub Date : 2025-09-22DOI: 10.1016/j.neulet.2025.138389
Alana Tercino Frias, Paloma Molina Hernandes, Helio Zangrossi Jr
Panic attacks, characterized by intense fear accompanied by autonomic and respiratory changes, can be experimentally modeled in humans and rodents by exposure to high concentrations of CO2. Acid-sensing ion channels (ASICs), particularly the ASIC1a subtype, are activated by decrease in pH and have been implicated in defensive responses triggered by hypercapnia. ASIC1a are found in key panic-associated areas such as the lateral wings of the dorsal raphe nucleus (lwDRN) and the dorsal periaqueductal gray (dPAG). Here, we first investigated whether ASIC1a channels in the lwDRN modulate the expression of panic-associated escape response in mice. C57BL/6 mice received intra-lwDRN injections of psalmotoxin-1 (Pstx-1; 12.5 or 25 ηg/50 ηL), a selective ASIC1a blocker, and were exposed to 20% CO2. ASIC1a blockade significantly reduced escape behavior without affecting baseline locomotion, suggesting a panicolytic-like effect. This effect was site-specific and abolished by intra-dPAG administration of WAY100635 (0.74 ηmol/50 ηL), a 5-HT1A receptor antagonist. Our study provides novel evidence that ASIC1a channels in the lwDRN contribute to CO2-evoked escape responses and that this modulation depends on serotonergic signaling via 5-HT1A receptors in the dPAG. These findings offer new insights into the neurobiology of panic attacks paving the way for the development of more precise treatments for PD.
{"title":"Blockade of acid-sensing ion channels 1a in the mice dorsal raphe nucleus inhibits panic-like responses: Role of 5-HT1A receptors in the dorsal periaqueductal gray","authors":"Alana Tercino Frias, Paloma Molina Hernandes, Helio Zangrossi Jr","doi":"10.1016/j.neulet.2025.138389","DOIUrl":"10.1016/j.neulet.2025.138389","url":null,"abstract":"<div><div>Panic attacks, characterized by intense fear accompanied by autonomic and respiratory changes, can be experimentally modeled in humans and rodents by exposure to high concentrations of CO<sub>2</sub>. Acid-sensing ion channels (ASICs), particularly the ASIC1a subtype, are activated by decrease in pH and have been implicated in defensive responses triggered by hypercapnia. ASIC1a are found in key panic-associated areas such as the lateral wings of the dorsal raphe nucleus (lwDRN) and the dorsal periaqueductal gray (dPAG). Here, we first investigated whether ASIC1a channels in the lwDRN modulate the expression of panic-associated escape response in mice. C57BL/6 mice received intra-lwDRN injections of psalmotoxin-1 (Pstx-1; 12.5 or 25 ηg/50 ηL), a selective ASIC1a blocker, and were exposed to 20% CO<sub>2</sub>. ASIC1a blockade significantly reduced escape behavior without affecting baseline locomotion, suggesting a panicolytic-like effect. This effect was site-specific and abolished by intra-dPAG administration of WAY100635 (0.74 ηmol/50 ηL), a 5-HT<sub>1A</sub> receptor antagonist. Our study provides novel evidence that ASIC1a channels in the lwDRN contribute to CO<sub>2</sub>-evoked escape responses and that this modulation depends on serotonergic signaling via 5-HT<sub>1A</sub> receptors in the dPAG. These findings offer new insights into the neurobiology of panic attacks paving the way for the development of more precise treatments for PD.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"867 ","pages":"Article 138389"},"PeriodicalIF":2.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138070","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}
Pub Date : 2025-09-22DOI: 10.1016/j.neulet.2025.138390
Bin Luo , Yu Zheng , Qi Miao , Yimin Zhang , Ye Lei , Qingyun Xu , Wenwu Li , Jingao Yu , Xiao Zhu , Jianlin Yuan , Huiyuan Zhu
Cerebral ischemia–reperfusion injury (CIRI) is a cerebrovascular disorder with high rates of incidence, disability, and death. It has been identified that Salvia miltiorrhiza and safflower have a protective effect in CIRI. However, the mechanisms of which remain to be elucidated. In this study, we investigated the protective mechanisms of the components of Salvia miltiorrhiza and safflower in CIRI, based on the TLR4/NF-κB signaling pathway. Sprague Dawley (SD) rats were used to establish the rat middle cerebral artery occlusion/reperfusion (MACO/R) model by the suture method. Drugs were injected intraperitoneally at 0 and 2 h, followed by once-daily treatment for 3 days. Neurological function and the volume of brain infarction were evaluated, and the pathological changes in brain tissue were examined using HE staining. ELISA kits were used to detect the concentrations of TNF-α and IL-6, while RT-qPCR, Western blot, and immunofluorescence were employed to evaluate the mRNA and protein expression in brain tissue. Following a combination of tanshinone IIA and hydroxy safflower yellow A treatment, our findings indicated that cerebral infarct volume and neurological deficits were reduced. The findings of HE staining revealed an improvement in cerebral histopathological damage in rats with MCAO/R. The levels of TNF-α and IL-6 in serum, as well as the expression of TLR4 and NF-κB in rat brains, were significantly reduced (P < 0.0001). Taken together, these results indicate that the combination of tanshinone ⅡA and hydroxyl safflower yellow A may exhibit a neuroprotective effect on cerebral I/R injury in rats by activating the TLR4/NF-κB signaling pathway.
{"title":"Tanshinone IIA and hydroxy safflower yellow A reduce cerebral injury via TLR4/NF-κB pathway in rats","authors":"Bin Luo , Yu Zheng , Qi Miao , Yimin Zhang , Ye Lei , Qingyun Xu , Wenwu Li , Jingao Yu , Xiao Zhu , Jianlin Yuan , Huiyuan Zhu","doi":"10.1016/j.neulet.2025.138390","DOIUrl":"10.1016/j.neulet.2025.138390","url":null,"abstract":"<div><div>Cerebral ischemia–reperfusion injury (CIRI) is a cerebrovascular disorder with high rates of incidence, disability, and death. It has been identified that Salvia miltiorrhiza and safflower have a protective effect in CIRI. However, the mechanisms of which remain to be elucidated. In this study, we investigated the protective mechanisms of the components of Salvia miltiorrhiza and safflower in CIRI, based on the TLR4/NF-κB signaling pathway. Sprague Dawley (SD) rats were used to establish the rat middle cerebral artery occlusion/reperfusion (MACO/R) model by the suture method. Drugs were injected intraperitoneally at 0 and 2 h, followed by once-daily treatment for 3 days. Neurological function and the volume of brain infarction were evaluated, and the pathological changes in brain tissue were examined using HE staining. ELISA kits were used to detect the concentrations of TNF-α and IL-6, while RT-qPCR, Western blot, and immunofluorescence were employed to evaluate the mRNA and protein expression in brain tissue. Following a combination of tanshinone IIA and hydroxy safflower yellow A treatment, our findings indicated that cerebral infarct volume and neurological deficits were reduced. The findings of HE staining revealed an improvement in cerebral histopathological damage in rats with MCAO/R. The levels of TNF-α and IL-6 in serum, as well as the expression of TLR4 and NF-κB in rat brains, were significantly reduced (P < 0.0001). Taken together, these results indicate that the combination of tanshinone ⅡA and hydroxyl safflower yellow A may exhibit a neuroprotective effect on cerebral I/R injury in rats by activating the TLR4/NF-κB signaling pathway.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"867 ","pages":"Article 138390"},"PeriodicalIF":2.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138080","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}
Pub Date : 2025-09-21DOI: 10.1016/j.neulet.2025.138385
Chunyu Zhou , Yulin Wang , Longfei Zuo , Yufan Miao , Wenjie Li , Xing Li , Yuan Xue , Mengxin Li
Alzheimer’s disease (AD) is the most common primary progressive neurodegenerative disorder, with inflammatory responses involved in its onset and progression. Vitamin D (VD) is known for its health benefits, including antioxidant effects. Recently, Deglycase protein 1 (DJ-1/PARK7) has been shown to potentially regulate in antioxidant activity and inflammation regulation. In this study, we investigated the therapeutic effects of VD3 (30 IU/g/w) in Dj-1 knockdown APPswe/PS1E9 (APP/PS1) mice. Pathological changes were assessed using the Morris water maze and Barnes maze, as well as immunofluorescence, thioflavin S staining, Nissl staining, TUNEL staining, Western blot, and RT-PCR. The results demonstrated that VD3 significantly ameliorated cognitive deficits and attenuated AD-like pathology in APP/PS1 mice. Moreover, VD3 upregulated DJ-1 expression and suppressed neuroinflammation and neuronal pyroptosis by modulating the NF-κB/NLRP3/caspase-1 and caspase-3/GSDME signaling pathways. Collectively, these findings suggest that DJ-1 mediate these protective effects, as its knockdown reversed VD3-induced improvements in neuroinflammation and neuronal pyroptosis, implicating that DJ-1 is a crucial modulator in the effects of VD3 on Alzheimer’s disease pathology.
{"title":"Vitamin D3 alleviates AD-like pathology in APP/PS1 mice by inhibiting pyroptosis and neuroinflammation via DJ-1/PARK7","authors":"Chunyu Zhou , Yulin Wang , Longfei Zuo , Yufan Miao , Wenjie Li , Xing Li , Yuan Xue , Mengxin Li","doi":"10.1016/j.neulet.2025.138385","DOIUrl":"10.1016/j.neulet.2025.138385","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is the most common primary progressive neurodegenerative disorder, with inflammatory responses involved in its onset and progression. Vitamin D (VD) is known for its health benefits, including antioxidant effects. Recently, Deglycase protein 1 (DJ-1/<em>PARK7</em>) has been shown to potentially regulate in antioxidant activity and inflammation regulation. In this study, we investigated the therapeutic effects of VD<sub>3</sub> (30 IU/g/w) in <em>Dj-1</em> knockdown APPswe/PS1E9 (APP/PS1) mice. Pathological changes were assessed using the Morris water maze and Barnes maze, as well as immunofluorescence, thioflavin S staining, Nissl staining, TUNEL staining, Western blot, and RT-PCR. The results demonstrated that VD<sub>3</sub> significantly ameliorated cognitive deficits and attenuated AD-like pathology in APP/PS1 mice. Moreover, VD<sub>3</sub> upregulated DJ-1 expression and suppressed neuroinflammation and neuronal pyroptosis by modulating the NF-κB/NLRP3/caspase-1 and caspase-3/GSDME signaling pathways. Collectively, these findings suggest that DJ-1 mediate these protective effects, as its knockdown reversed VD<sub>3</sub>-induced improvements in neuroinflammation and neuronal pyroptosis, implicating that DJ-1 is a crucial modulator in the effects of VD<sub>3</sub> on Alzheimer’s disease pathology.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"867 ","pages":"Article 138385"},"PeriodicalIF":2.0,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131375","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}
Pub Date : 2025-09-21DOI: 10.1016/j.neulet.2025.138388
Carlos J. Gómez-Ariza , Javier Pacios
While many tDCS studies have focused on enhancing inhibitory control, only a few have employed tDCS to disrupt the neural activity of specific brain regions and gain understanding of their contribution to inhibitory control. This mini-review describes and discusses the results of studies that specifically applied cathodal tDCS over the right dorsolateral prefrontal cortex. The majority of these studies employed variants of experimental procedures that assessed the ability to inhibit either inappropriate motor responses or competing memories during selective retrieval. In both domains, action stopping and memory downregulation, neuroimaging research has shown that successful inhibitory control engages common areas within the right lateral prefrontal cortex. Strikingly, although a significant proportion of the reviewed studies reported behavioral effects that can be interpreted as a consequence of hindering inhibitory control, they have not been previously considered or discussed altogether despite its theoretical and methodological implications. This consistent disruptive effect challenges the common belief that cathodal tDCS is ineffective in modulating performance when applied to prefrontal regions. Additionally, the results provide causal evidence that supports the proposed role of the right lateral prefrontal cortex in a domain-general inhibitory system, particularly in relation to stopping actions and downregulating competing memories.
{"title":"Mini-Review: Cathodal tDCS over the right prefrontal cortex and inhibitory control: Pinpointing an electrode montage to disrupt a domain-general system","authors":"Carlos J. Gómez-Ariza , Javier Pacios","doi":"10.1016/j.neulet.2025.138388","DOIUrl":"10.1016/j.neulet.2025.138388","url":null,"abstract":"<div><div>While many tDCS studies have focused on enhancing inhibitory control, only a few have employed tDCS to disrupt the neural activity of specific brain regions and gain understanding of their contribution to inhibitory control. This mini-review describes and discusses the results of studies that specifically applied cathodal tDCS over the right dorsolateral prefrontal cortex. The majority of these studies employed variants of experimental procedures that assessed the ability to inhibit either inappropriate motor responses or competing memories during selective retrieval. In both domains, action stopping and memory downregulation, neuroimaging research has shown that successful inhibitory control engages common areas within the right lateral prefrontal cortex. Strikingly, although a significant proportion of the reviewed studies reported behavioral effects that can be interpreted as a consequence of hindering inhibitory control, they have not been previously considered or discussed altogether despite its theoretical and methodological implications. This consistent disruptive effect challenges the common belief that cathodal tDCS is ineffective in modulating performance when applied to prefrontal regions. Additionally, the results provide causal evidence that supports the proposed role of the right lateral prefrontal cortex in a domain-general inhibitory system, particularly in relation to stopping actions and downregulating competing memories.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"867 ","pages":"Article 138388"},"PeriodicalIF":2.0,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131370","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}
Pub Date : 2025-09-20DOI: 10.1016/j.neulet.2025.138387
Ying Li , Chen Zhang , Limin Han , Zhao Qian
Tetrodotoxin (TTX)-sensitive/Nav1.7- and TTX-resistive/Nav1.8 Na+ channels contribute to neuroexcitation in the sensory neurons of the nodose ganglion (NG); however, their specific roles remain debatable. Therefore, we aimed to study the action potential (AP) elicited from NG neurons isolated from adult rats and simulated by a dynamic current clamp (DCC) using gNa0/Nav1.7 and/or gNa1/Nav1.8 injection. We trained and tuned the voltage-dependent profiles of the Na+ current generated from the DCC using the Hodgkin–Huxley/Vandenberg models to match the AP parameters elicited by a brief pulse. A- or C-type AP could be simulated using DCC by applying gNa0 or gNa0/gNa1 alongside reduced gNa0 to avoid overshooting the up-stroke. This indicates the indispensability of these two Na+ channels for shaping the AP trajectory with tight orchestration. The hump over the repolarization period featuring C-type neurons could be generated using DCC by adding gNa1 in this cellular model. Furthermore, both A- and C-type repeated discharges can be simulated using gNa0 or gNa1 with a reduced gNa0. Similar experiments were performed on human embryonic kidney 293 cells with stable Nav1.7 expression to mimic A-type-like conditions for further verification. Both A- and C-type-like APs were simulated in this expression system by adding gNa0 or gNa0/gNa1. Therefore, Nav1.7/Nav1.8 is crucial in shaping the AP trajectory, with specific timing for Nav1.8 activation to retain neuroexcitation in the sensory nervous system. Additionally, this pilot study will establish a fundamental base for the pharmacological screening of targeted ion channels and validate the disease-based mechanism in cardiology and neuroscience.
{"title":"Dynamic current-clamp unveiling the indispensable interplay between Nav1.7 and Nav1.8 for shaping action potential trajectory and retaining neuroexcitation of visceral sensory neurons","authors":"Ying Li , Chen Zhang , Limin Han , Zhao Qian","doi":"10.1016/j.neulet.2025.138387","DOIUrl":"10.1016/j.neulet.2025.138387","url":null,"abstract":"<div><div>Tetrodotoxin (TTX)-sensitive/Nav1.7- and TTX-resistive/Nav1.8 Na<sup>+</sup> channels contribute to neuroexcitation in the sensory neurons of the nodose ganglion (NG); however, their specific roles remain debatable. Therefore, we aimed to study the action potential (AP) elicited from NG neurons isolated from adult rats and simulated by a dynamic current clamp (DCC) using gNa0/Nav1.7 and/or gNa1/Nav1.8 injection. We trained and tuned the voltage-dependent profiles of the Na<sup>+</sup> current generated from the DCC using the Hodgkin–Huxley/Vandenberg models to match the AP parameters elicited by a brief pulse. A- or C-type AP could be simulated using DCC by applying gNa0 or gNa0/gNa1 alongside reduced gNa0 to avoid overshooting the up-stroke. This indicates the indispensability of these two Na<sup>+</sup> channels for shaping the AP trajectory with tight orchestration. The hump over the repolarization period featuring C-type neurons could be generated using DCC by adding gNa1 in this cellular model. Furthermore, both A- and C-type repeated discharges can be simulated using gNa0 or gNa1 with a reduced gNa0. Similar experiments were performed on human embryonic kidney 293 cells with stable Nav1.7 expression to mimic A-type-like conditions for further verification. Both A- and C-type-like APs were simulated in this expression system by adding gNa0 or gNa0/gNa1. Therefore, Nav1.7/Nav1.8 is crucial in shaping the AP trajectory, with specific timing for Nav1.8 activation to retain neuroexcitation in the sensory nervous system. Additionally, this pilot study will establish a fundamental base for the pharmacological screening of targeted ion channels and validate the disease-based mechanism in cardiology and neuroscience.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"867 ","pages":"Article 138387"},"PeriodicalIF":2.0,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145125176","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}
Pub Date : 2025-09-17DOI: 10.1016/j.neulet.2025.138386
Debao Wu , Zhenghao Li , Xiaoyun Lu , Li Li , Wenxiu Dai , Xuemin Wang , Liang Zhang
Peripheral nerve myelination critically relies on the timely and efficient delivery of myelin proteins and membranes. Although Coat Protein Complex II (COPII) is a canonical vesicular trafficking machinery, the cell-type-specific functions of its components in Schwann cell remain uncharacterized. Here, we show that Sec13, an essential component of COPII, is abundantly expressed in Schwann cells of the sciatic nerve. Furthermore, conditional knockout of Sec13 in Schwann cells (Sec13cKO) results in hindlimb weakness and lethality in mutant mice. Morphological analysis revealed that Sec13cKO nerves are thin and translucent, with immunostaining for myelin basic protein showing a progressive reduction in myelin coverage. Transmission electron microscopy demonstrated fewer myelinated axons, loosely wrapped or absent lamellae, and an increased g–ratio, indicating thinner, poorly compacted sheaths. At the cellular level, Sec13 deletion caused a marked decrease in Sox10+ Schwann cell density from P7 onward, concomitant with reduced proliferation of Sox10+, Sox2+, and Oct6+ populations, and a significant increase of cell death at P14. Together, these findings suggest that Sec13 is indispensable for Schwann cell proliferation, survival, and execution of the myelination program.
{"title":"COPII component Sec13 is required for peripheral myelination and Schwann cell maintenance","authors":"Debao Wu , Zhenghao Li , Xiaoyun Lu , Li Li , Wenxiu Dai , Xuemin Wang , Liang Zhang","doi":"10.1016/j.neulet.2025.138386","DOIUrl":"10.1016/j.neulet.2025.138386","url":null,"abstract":"<div><div>Peripheral nerve myelination critically relies on the timely and efficient delivery of myelin proteins and membranes. Although Coat Protein Complex II (COPII) is a canonical vesicular trafficking machinery, the cell-type-specific functions of its components in Schwann cell remain uncharacterized. Here, we show that Sec13, an essential component of COPII, is abundantly expressed in Schwann cells of the sciatic nerve. Furthermore, conditional knockout of Sec13 in Schwann cells (<em>Sec13</em>cKO) results in hindlimb weakness and lethality in mutant mice. Morphological analysis revealed that <em>Sec13</em>cKO nerves are thin and translucent, with immunostaining for myelin basic protein showing a progressive reduction in myelin coverage. Transmission electron microscopy demonstrated fewer myelinated axons, loosely wrapped or absent lamellae, and an increased <em>g</em>–ratio, indicating thinner, poorly compacted sheaths. At the cellular level, <em>Sec13</em> deletion caused a marked decrease in Sox10<sup>+</sup> Schwann cell density from P7 onward, concomitant with reduced proliferation of Sox10<sup>+</sup>, Sox2<sup>+</sup>, and Oct6<sup>+</sup> populations, and a significant increase of cell death at P14. Together, these findings suggest that Sec13 is indispensable for Schwann cell proliferation, survival, and execution of the myelination program.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"867 ","pages":"Article 138386"},"PeriodicalIF":2.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092198","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}
Pub Date : 2025-09-08DOI: 10.1016/j.neulet.2025.138382
Zehra Sezgin , Hale Sayan Ozacmak , Inci Turan
Stress triggers neuroendocrine and physiological changes, often resulting in cognitive impairments and heightened anxiety. This study aims to investigate the effects of acute stress and epinephrine administration on learning, memory, and anxiety-like behavior, as well as their impact on proinflammatory cytokines, neurogranin expression, and brain energy metabolism.
In this study, three experimental groups were established, each comprising eight rats: control, acute stress, and acute stress combined with epinephrine. The acute stress model consisted of 60 min of restraint stress. Epinephrine was administered following the stress procedure. Memory performance was evaluated using the Morris water maze (MWM), while anxiety-like behavior was assessed through the open field test (OFT). Levels of proinflammatory cytokines, neurogranin, MCT2, glycogen, and corticosterone levels were measured.
In the probe test, the acute stress group exhibited significantly poorer performance compared to the control group. Epinephrine administration induced anxiogenic effects in stressed animals. Neurogranin and glycogen levels in the hippocampus and prefrontal cortex were significantly reduced in rats exposed to stress + epinephrine compared to controls. MCT2 expression was also significantly lower in the stress + epinephrine group. IL-1β level was elevated in the prefrontal cortex of the stress + epinephrine group compared to the control group, while, TNF-α levels were found to be elevated in the hippocampus.
Epinephrine administration in conjunction with acute stress has been shown to reduce hippocampal levels of neurogranin, MCT-2, and glycogen, while simultaneously increasing proinflammatory cytokine levels. These molecular alterations appear to contribute to both impaired hippocampal-dependent learning and heightened anxiety-like behavior.
压力会引发神经内分泌和生理变化，通常会导致认知障碍和焦虑加剧。本研究旨在探讨急性应激和肾上腺素给药对学习、记忆和焦虑样行为的影响，以及它们对促炎细胞因子、神经颗粒蛋白表达和大脑能量代谢的影响。本研究建立3个实验组，每组8只大鼠：对照组、急性应激组、急性应激联合肾上腺素组。急性应力模型为60 min约束应力。在应激过程后给予肾上腺素。采用Morris水迷宫（MWM）评价记忆表现，采用open field test （OFT）评价类焦虑行为。测量促炎细胞因子、神经颗粒蛋白、MCT2、糖原和皮质酮水平。在探针测试中，急性应激组的表现明显低于对照组。肾上腺素给药诱导应激动物产生焦虑效应。与对照组相比，暴露于压力 + 肾上腺素的大鼠海马和前额皮质的神经颗粒蛋白和糖原水平显著降低。应激 + 肾上腺素组MCT2表达也显著降低。与对照组相比，应激 + 肾上腺素组前额叶皮层IL-1β水平升高，而海马中TNF-α水平升高。肾上腺素与急性应激联合使用已被证明可以降低海马神经颗粒蛋白、MCT-2和糖原的水平，同时增加促炎细胞因子的水平。这些分子改变似乎导致了海马依赖性学习受损和焦虑样行为加剧。
{"title":"Acute restraint stress and epinephrine administration disrupt cognitive and emotional functions in male rats via modulation of proinflammatory cytokines, MCT-2, and neurogranin","authors":"Zehra Sezgin , Hale Sayan Ozacmak , Inci Turan","doi":"10.1016/j.neulet.2025.138382","DOIUrl":"10.1016/j.neulet.2025.138382","url":null,"abstract":"<div><div>Stress triggers neuroendocrine and physiological changes, often resulting in cognitive impairments and heightened anxiety. This study aims to investigate the effects of acute stress and epinephrine administration on learning, memory, and anxiety-like behavior, as well as their impact on proinflammatory cytokines, neurogranin expression, and brain energy metabolism.</div><div>In this study, three experimental groups were established, each comprising eight rats: control, acute stress, and acute stress combined with epinephrine. The acute stress model consisted of 60 min of restraint stress. Epinephrine was administered following the stress procedure. Memory performance was evaluated using the Morris water maze (MWM), while anxiety-like behavior was assessed through the open field test (OFT). Levels of proinflammatory cytokines, neurogranin, MCT2, glycogen, and corticosterone levels were measured.</div><div>In the probe test, the acute stress group exhibited significantly poorer performance compared to the control group. Epinephrine administration induced anxiogenic effects in stressed animals. Neurogranin and glycogen levels in the hippocampus and prefrontal cortex were significantly reduced in rats exposed to stress + epinephrine compared to controls. MCT2 expression was also significantly lower in the stress + epinephrine group. IL-1β level was elevated in the prefrontal cortex of the stress + epinephrine group compared to the control group, while, TNF-α levels were found to be elevated in the hippocampus.</div><div>Epinephrine administration in conjunction with acute stress has been shown to reduce hippocampal levels of neurogranin, MCT-2, and glycogen, while simultaneously increasing proinflammatory cytokine levels. These molecular alterations appear to contribute to both impaired hippocampal-dependent learning and heightened anxiety-like behavior.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"867 ","pages":"Article 138382"},"PeriodicalIF":2.0,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033700","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}
Pub Date : 2025-09-07DOI: 10.1016/j.neulet.2025.138368
Xin-Xin Wei , Hao-Jun Liu , Zhou-Zan Liao , Xiang-Xiang Li , Liang-Liang Ma , Wei Zou , Gui-Juan Zhou , Xiao-Qing Tang
Radiation-induced brain injury (RIBI) is a prevalent complication following radiotherapy for head and neck tumors, and its effective therapeutic strategies are lacking. Ferroptosis, an iron-dependent cell death, has recently emerged as an important mechanism of radiation-induced cell death. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuro-interventional technique with antioxidant and neuroprotective properties. The present study aimed to explore whether rTMS attenuates RIBI by inhibiting ferroptosis. We demonstrated that rTMS alleviated neuronal injury and death in the hippocampus of RIBI rats. rTMS also improved the mitochondrial ultrastructure in the hippocampus of RIBI rats. Moreover, rTMS reduces the accumulation of iron, reactive oxygen species (ROS), and lipid peroxidation products in the hippocampus of RIBI rats. In addition, rTMS increased the expression of Glutathione peroxidase 4 (GPX4), Solute carrier family 7 member 11 (SLC7A11), and Ferritin heavy chain 1 (FTH1) and decreased the expression of Acyl-CoA synthetase long-chain family member 4 (ACSL4). These findings indicate that rTMS attenuates RIBI and the underlying mechanism involves the inhibition of ferroptosis. Our study highlights rTMS as a potentially effective therapeutic intervention for treating RIBI. The mechanistic insights shed light on the role of ferroptosis and expand our knowledge of its potential as a therapeutic target for diseases beyond RIBI.
{"title":"Repetitive transcranial magnetic stimulation alleviates radiation-induced brain injury in rats: involving the inhibition of ferroptosis","authors":"Xin-Xin Wei , Hao-Jun Liu , Zhou-Zan Liao , Xiang-Xiang Li , Liang-Liang Ma , Wei Zou , Gui-Juan Zhou , Xiao-Qing Tang","doi":"10.1016/j.neulet.2025.138368","DOIUrl":"10.1016/j.neulet.2025.138368","url":null,"abstract":"<div><div>Radiation-induced brain injury (RIBI) is a prevalent complication following radiotherapy for head and neck tumors, and its effective therapeutic strategies are lacking. Ferroptosis, an iron-dependent cell death, has recently emerged as an important mechanism of radiation-induced cell death. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuro-interventional technique with antioxidant and neuroprotective properties. The present study aimed to explore whether rTMS attenuates RIBI by inhibiting ferroptosis. We demonstrated that rTMS alleviated neuronal injury and death in the hippocampus of RIBI rats. rTMS also improved the mitochondrial ultrastructure in the hippocampus of RIBI rats. Moreover, rTMS reduces the accumulation of iron, reactive oxygen species (ROS), and lipid peroxidation products in the hippocampus of RIBI rats. In addition, rTMS increased the expression of Glutathione peroxidase 4 (GPX4), Solute carrier family 7 member 11 (SLC7A11), and Ferritin heavy chain 1 (FTH1) and decreased the expression of Acyl-CoA synthetase long-chain family member 4 (ACSL4). These findings indicate that rTMS attenuates RIBI and the underlying mechanism involves the inhibition of ferroptosis. Our study highlights rTMS as a potentially effective therapeutic intervention for treating RIBI. The mechanistic insights shed light on the role of ferroptosis and expand our knowledge of its potential as a therapeutic target for diseases beyond RIBI.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"867 ","pages":"Article 138368"},"PeriodicalIF":2.0,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030286","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}
Pub Date : 2025-09-05DOI: 10.1016/j.neulet.2025.138375
Xiangxi Kong , Zhijie Fan , Tang Rui , Yuxuan Qi , Xuening Wang , Anran Zhang , Xin Chen , Yajin Liao , Jun Ma
Pain and pain-related psychiatric diseases affect approximately one-third of the global population, and effective treatment remains a lack of options. NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome is regarded as a potential therapeutic target for managing pain and related psychiatric diseases. Our previous research reported that 1,2,4-trimethoxybenzene (1,2,4-TTB) effectively inhibited NLRP3 inflammasome activity. Therefore, we further investigated the role of 1,2,4-TTB in the treatment of pain and its associated psychiatric disorders. In this study, we evaluated the effects of 1,2,4-TTB (200 mg.kg−1) by intragastric administration on mechanical pain, anxiety and depression-like behaviors using Complete Freund’s Adjuvant (CFA) induced acute and chronic inflammatory pain mouse models. Furthermore, NLRP3 inflammasome activation was assessed through western blotting. Immunofluorescence was employed to observe the number of macrophages and microglia. Results indicated that 1,2,4-TTB markedly relieved mechanical pain in acute and chronic pain mouse models. 1,2,4-TTB also improved anxiety and depression-like behaviors in pain mouse models. Additionally, NLRP3 inflammasome activation was dramatically suppressed by 1,2,4-TTB in pain mouse models. The macrophage and microglia activation were also inhibited by 1,2,4-TTB. Our research shows that 1,2,4-TTB attenuates both acute and chronic inflammatory pain as well as anxiety and depression-like behaviors. These findings suggest that 1,2,4-TTB is a promising therapeutic option for managing various types of pain, anxiety, and depression.
{"title":"1, 2, 4-trimethoxybenzene alleviates pain and related psychiatric disorders by inhibiting NLRP3 inflammasome activation","authors":"Xiangxi Kong , Zhijie Fan , Tang Rui , Yuxuan Qi , Xuening Wang , Anran Zhang , Xin Chen , Yajin Liao , Jun Ma","doi":"10.1016/j.neulet.2025.138375","DOIUrl":"10.1016/j.neulet.2025.138375","url":null,"abstract":"<div><div>Pain and pain-related psychiatric diseases affect approximately one-third of the global population, and effective treatment remains a lack of options. NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome is regarded as a potential therapeutic target for managing pain and related psychiatric diseases. Our previous research reported that 1,2,4-trimethoxybenzene (1,2,4-TTB) effectively inhibited NLRP3 inflammasome activity. Therefore, we further investigated the role of 1,2,4-TTB in the treatment of pain and its associated psychiatric disorders. In this study, we evaluated the effects of 1,2,4-TTB (200 <span><span>mg.kg</span><svg><path></path></svg></span><sup>−1</sup>) by intragastric administration on mechanical pain, anxiety and depression-like behaviors using Complete Freund’s Adjuvant (CFA) induced acute and chronic inflammatory pain mouse models. Furthermore, NLRP3 inflammasome activation was assessed through western blotting. Immunofluorescence was employed to observe the number of macrophages and microglia. Results indicated that 1,2,4-TTB markedly relieved mechanical pain in acute and chronic pain mouse models. 1,2,4-TTB also improved anxiety and depression-like behaviors in pain mouse models. Additionally, NLRP3 inflammasome activation was dramatically suppressed by 1,2,4-TTB in pain mouse models. The macrophage and microglia activation were also inhibited by 1,2,4-TTB. Our research shows that 1,2,4-TTB attenuates both acute and chronic inflammatory pain as well as anxiety and depression-like behaviors. These findings suggest that 1,2,4-TTB is a promising therapeutic option for managing various types of pain, anxiety, and depression.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"866 ","pages":"Article 138375"},"PeriodicalIF":2.0,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015940","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}
Pub Date : 2025-09-03DOI: 10.1016/j.neulet.2025.138374
Nikita V. Khotskin, Arseniy E. Izyurov, Alexander V. Kulikov
The lethal yellow (AY) mutation in the Raly-Agouti locus leads to ectopic expression of the agouti protein in the brain where it inhibits melanocortin receptors, causes obesity as well as alters some traits of adaptive behavior. In the present study we used the Phenomaster calorimetric module tool to compare the travel distance, food and O2 consumption as well as CO2 excretion in 12 weeks old males of C57BL/6- AY and C57BL/6 mice. The AY mutation did not affect travelled distance and food consumption. At the same time, this mutation significantly reduced O2 consumption and CO2 excretion which are the main indices of indirect calorimetry. This result suggests that the reduced energy expenditure is a cause of obesity in C57BL/6- AY mice. These mutant mice seem to use energy received with food in a more economical way compared to C57BL/6 mice. The results of the present study increase the impact of C57BL/6- AY mice as a convenient model of neural and molecular mechanisms of economical expenditure of energy resources.
{"title":"Lethal yellow mutation in the Raly-Agouti locus reduces the energy expenditure in male mice","authors":"Nikita V. Khotskin, Arseniy E. Izyurov, Alexander V. Kulikov","doi":"10.1016/j.neulet.2025.138374","DOIUrl":"10.1016/j.neulet.2025.138374","url":null,"abstract":"<div><div>The <em>lethal yellow (A<sup>Y</sup>)</em> mutation in the <em>Raly-Agouti</em> locus leads to ectopic expression of the agouti protein in the brain where it inhibits melanocortin receptors, causes obesity as well as alters some traits of adaptive behavior. In the present study we used the Phenomaster calorimetric module tool to compare the travel distance, food and O<sub>2</sub> consumption as well as CO<sub>2</sub> excretion in 12 weeks old males of C57BL/6- A<sup>Y</sup> and C57BL/6 mice. The <em>A<sup>Y</sup></em> mutation did not affect travelled distance and food consumption. At the same time, this mutation significantly reduced O<sub>2</sub> consumption and CO<sub>2</sub> excretion which are the main indices of indirect calorimetry. This result suggests that the reduced energy expenditure is a cause of obesity in C57BL/6- A<sup>Y</sup> mice. These mutant mice seem to use energy received with food in a more economical way compared to C57BL/6 mice. The results of the present study increase the impact of C57BL/6- A<sup>Y</sup> mice as a convenient model of neural and molecular mechanisms of economical expenditure of energy resources.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"866 ","pages":"Article 138374"},"PeriodicalIF":2.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004822","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号