Neurosci. Lett. [JOURNAL]
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200 papers
Regional differences in oxytocin and vasopressin 1a receptor functionality in mouse embryonic brain development.
Sommer E, Caldwell HK
Neurosci Lett · 2025 Nov · PMID 41057092 · Full text
There is mounting evidence that the oxytocin (Oxt) and vasopressin (Avp) systems contribute to early brain development. Work from transgenic mouse models as well as pharmacological manipulation of the Oxt and Avp systems...
There is mounting evidence that the oxytocin (Oxt) and vasopressin (Avp) systems contribute to early brain development. Work from transgenic mouse models as well as pharmacological manipulation of the Oxt and Avp systems suggests that signaling through the Oxt receptor (Oxtr) and the Avp 1a receptor (Avpr1a) during embryonic brain development affects behavior in adulthood. Unfortunately, at this time, very little is known or understood about where in the brain Oxtr and Avpr1a occurs during embryonic development or what the downstream consequences may be. To help provide some answers, Oxtr- and Avpr1a-stimulated G-protein coupled receptor binding assays were performed using guanosine 5'-(γ-thio)triphosphate, a non-hydrolyzable analog of guanosine triphosphate, to determine the functionality of the Oxtr and Avpr1a in both sexes at embryonic day (E) 14.5, E16.5, and E18.5. Based on previous work, we hypothesized that the Oxtr and Avpr1a would be functional in both sexes by E16.5 and activated by Oxt and Avp, respectively. The data suggest that while the Oxtr and Avpr1a are functional in both sexes starting at E16.5, where in the brain they are functional is not fully aligned with where there is known receptor binding. For the Oxtr, at E16.5, functional binding was observed in the ventricular and subventricular zones of the cortical and septal neuroepithelium and the amygdalar area, this shifted by E18.5 with functional binding observed only in the ventricular and subventricular septal neuroepithelium and the amygdalar area, with no functional binding observed in the ventricular and subventricular cortical neuroepithelium. For the Avpr1a, at E16.5, functional binding was only observed in the ventral hypothalamic area but by E18.5 functional binding was observed across numerous brain regions. Taken together, these data suggest that Oxtr and Avpr1a signaling is positioned to have site-specific effects on mouse brain development starting at E16.5.
Increased reactive oxygen species in the spinal cord drive renal sympathetic vasomotor activity in Goldblatt hypertensive rats.
Tagliapietra FM, Milanez MIO, da Luz Abreu E … +3 more , Nishi EE, Bergamaschi CT, Campos RR
Neurosci Lett · 2025 Nov · PMID 41047068 · Publisher ↗
Increased production of reactive oxygen species (ROS) in brain regions contributes to the sympathetic vasomotor overactivity in Goldblatt hypertension (2K1C). Previously, studies reported that overexpression of spinal an...
Increased production of reactive oxygen species (ROS) in brain regions contributes to the sympathetic vasomotor overactivity in Goldblatt hypertension (2K1C). Previously, studies reported that overexpression of spinal angiotensin II (Ang II) type I (AT1) contributes to sympathetic vasomotor overactivation in 2K1C rats. Considering that Ang II leads to an imbalance of oxidative stress, the present study evaluated the role of spinal ROS in regulating the activity of sympathetic preganglionic neurons in 2K1C rats. Hypertension was induced by clipping the left renal artery. Six weeks after clipping, a catheter was inserted into the subarachnoid space and advanced to the T10-11 vertebral level in urethane-anaesthetized rats. The effects of intrathecal (i.t.) injection of Tempol on mean arterial pressure (MAP), heart rate (HR), renal and splanchnic sympathetic nerve activity (rSNA and sSNA, respectively) were evaluated over 60 consecutive minutes. mRNA expression of enzymes involved in oxidative balance was analyzed in the spinal cord. In addition, spinal ROS abundance was quantified by the DHE fluorescence method. An increase in ROS production was observed in the thoracic region of 2K1C rats compared to the control group. I.t. administration of Tempol triggered a significant and preferential reduction in rSNA in the 2K1C but not in control rats. Thus, the data suggest that renal sympathoexcitation in 2K1C rats was associated with an increase in oxidative imbalance in the spinal cord, particularly in sympathetic preganglionic neurons that drive rSNA.
Combined chronic oral methylphenidate and fluoxetine treatment increases CB1 receptor density in the somatosensory forelimb region.
Lantry AM, Lu H, Marion M … +7 more , Hamilton J, Richardson B, Quattrin T, Mastrandrea LD, Hadjiargyrou M, Komatsu D, Thanos PK
Neurosci Lett · 2025 Dec · PMID 41046046 · Publisher ↗
Methylphenidate (MP) is a psychostimulant commonly prescribed for attention-deficit/hyperactivity disorder (ADHD), and Fluoxetine (FLX) is a selective serotonin reuptake inhibitor (SSRI) commonly prescribed to treat depr...
Methylphenidate (MP) is a psychostimulant commonly prescribed for attention-deficit/hyperactivity disorder (ADHD), and Fluoxetine (FLX) is a selective serotonin reuptake inhibitor (SSRI) commonly prescribed to treat depression and anxiety disorders. Both are shown to impact neurochemistry and behavior, but little is known about their individual and combined impacts on the endocannabinoid system (ECS). We examined the effects of MP and FLX, both as separate treatments and in combination, on cannabinoid receptor type 1 (CB1) binding in several key brain regions of interest. Male rats were treated with either water, MP, FLX, or MP + FLX via a previously established drinking paradigm for three months. Brains were harvested, and [H] SR141716A in vitro autoradiography was performed to quantify CB1 binding. The combined treatment of MP + FLX showed significantly higher [H] SR141716A binding compared to the water, MP, and FLX groups in the somatosensory forelimb (S(FL)) region. This indicates an ability of the common co-usage of MP and FLX to increase CB1 levels in the somatosensory cortex: a region of the brain required for the processing of sensory information.
Dexmedetomidine improves postoperative cognitive dysfunction via regulating Adrb2/Pkg: Dexmedetomidine against postoperative cognitive dysfunction.
Chen C, Han H, Li H … +2 more , Zhang Z, Lv Y
Neurosci Lett · 2025 Nov · PMID 41043682 · Publisher ↗
BACKGROUND: Postoperative cognitive dysfunction (POCD) refers to postoperative neurological complications in patients, thus affecting patients' normal daily life. PURPOSE: Our study aimed to confirm whether Adrb2/Pkg are...
BACKGROUND: Postoperative cognitive dysfunction (POCD) refers to postoperative neurological complications in patients, thus affecting patients' normal daily life. PURPOSE: Our study aimed to confirm whether Adrb2/Pkg are involved in the protective effect of Dexmedetomidine (Dex) against POCD in rats. METHODS: The targets for Dex against POCD were screened by online databases. An POCD rat model was constructed, and the Morris water maze tests were conducted to evaluate the cognitive function of POCD rats. The inflammatory markers (IL-6, TNF-α, and IL-13) were recorded, and the levels of Adrb2 and Pkg in hippocampus tissue were detected using RT-qPCR. The key targets Adrb2/Pkg were verified through the LPS-induced inflammatory BV-2 cell model. RESULTS: Network pharmacology analysis predicted that Adrb2 and Pkg were the key genes of Dex against POCD. Dex treatment improved learning and memory skills of POCD rats. In vitro and in vivo experiments showed that Dex treatment alleviated inflammation, and upregulated Adrb2 and Pkg mRNA levels of POCD rats and inflammatory BV-2 cell line. Silencing Adrb2/Pkg reversed the apoptosis suppression in LPS-induced inflammatory BV-2 cells caused by Dex. CONCLUSION: The Adrb2/Pkg could potentially be the mechanism by which Dex protects POCD rats from cognitive impairment.
Hydrogen sulfide protects against hippocampal neuronal apoptosis in aged rats with postoperative cognitive dysfunction by promoting m6A methylation.
Wang B, Wen Y, Tang Y … +1 more , Li M
Neurosci Lett · 2025 Nov · PMID 41038564 · Publisher ↗
PURPOSE: To explore the potential involvement of m6A methylation in the neuroprotective mechanism of HS against hippocampus neuronal apoptosis in aged rats with POCD. METHODS: Sprague-Dawley rats (18-20 months) were subj...
PURPOSE: To explore the potential involvement of m6A methylation in the neuroprotective mechanism of HS against hippocampus neuronal apoptosis in aged rats with POCD. METHODS: Sprague-Dawley rats (18-20 months) were subjected to anesthesia and laparotomy surgery to establish an animal model of POCD. The Open Field, Y-maze, and Novel Object Recognition tests assessed behavioral performance. Protein expression levels were analyzed using Western blot analysis, and neuronal apoptosis was analyzed using TUNEL staining. RESULTS: NaHS (100 μmol/kg) significantly increased the alternation ratio of the Y-maze test and the discrimination index of the NOR test, reduced hippocampal neuronal apoptosis, indicated by decreased TUNEL-positive neurons and modulated the expression of apoptosis-related protein markers (Bcl-2 was upregulated and Bax/Cleaved caspase-3 were downregulated). Furthermore, NaHS restored reduced mA RNA methylation levels and corrected the disturbed expression of mA-related enzymes (METTL3, METTL14, YTHDF1, YTHDF3, FTO, ALKBH5) in the hippocampus of aged rats with POCD. CONCLUSION: HS shows neuroprotective effects by mitigating hippocampal neuronal apoptosis and restoring mA RNA methylation in the hippocampus of aged rats with POCD. These findings provide preclinical evidence that HS may serve as a potential therapeutic agent for the prevention of POCD.
GABAergic disinhibition through the STING-dependent autophagic pathway in the dorsal horn underlies diabetic neuropathic pain pathogenesis.
Zhao YJ, Bai HZ, Wang YN … +6 more , Liu YK, Zhao LB, Li Z, Li HZ, Wang XL, Liu P
Neurosci Lett · 2025 Nov · PMID 41027494 · Publisher ↗
Our previous study demonstrated that STING/ATG5-mediated autophagy in the spinal dorsal horn contributes to diabetic neuropathic pain (DNP), although the underlying mechanisms remained unclear. In this study, we investig...
Our previous study demonstrated that STING/ATG5-mediated autophagy in the spinal dorsal horn contributes to diabetic neuropathic pain (DNP), although the underlying mechanisms remained unclear. In this study, we investigated how STING-driven autophagy leads to impaired spinal inhibition via lysosomal degradation of GABA receptors. In a rat model of DNP, spinal levels of STING and ATG5 were elevated, while P62, GABA receptor, and GABA receptor expression were reduced. Behavioral tests showed that intrathecal administration of a STING inhibitor increased mechanical pain thresholds and upregulated P62 and GABA receptors. Conversely, treatment with a STING agonist worsened hyperalgesia and further suppressed GABA receptor expression. Knockdown of ATG5 via siRNA similarly alleviated pain and restored GABA receptor levels. Interestingly, although the mTOR inhibitor rapamycin alleviated neuropathic pain, it unexpectedly increased spinal P62 expression compared to the DNP group. Administration of leupeptin, a lysosomal protease inhibitor, significantly increased paw withdrawal thresholds on days 1-3 and elevated GABA receptor expression, whereas the proteasomal inhibitor MG132 had no effect. These results demonstrate that STING/ATG5-mediated autophagy promotes DNP through autophagic-lysosomal degradation of GABA receptors, highlighting this pathway as a promising therapeutic target for treating diabetic neuropathic pain.
Cannabidiol engages the peripheral endogenous opioid system to produce analgesia in neuropathic mice.
de Almeida DL, Pinto Barra WC, Mendes Ferreira RC … +6 more , Fonseca FC, Dias Machado DP, Aguiar DD, Guimaraes FS, Gama Duarte ID, Lima Romero TR
Neurosci Lett · 2025 Nov · PMID 41022278 · Publisher ↗
Cannabidiol (CBD) has been getting attention from the scientific community regarding its potential for the treatment of different conditions, such as epilepsy, anxiety, and pain. This potential can be useful in clinical...
Cannabidiol (CBD) has been getting attention from the scientific community regarding its potential for the treatment of different conditions, such as epilepsy, anxiety, and pain. This potential can be useful in clinical practice as an alternative or as an adjuvant alongside conventional therapeutic approaches; however, its mechanisms of action should be best described for its more effective application. Thus, our study aimed to evaluate whether the peripheral opioid system is involved in the analgesic mechanism of cannabidiol administered systemically for the treatment of neuropathic pain. Male Swiss mice were subjected to the sciatic constriction injury, and their nociceptive threshold was evaluated using the mechanical paw pressure test. Cannabidiol 20 mg/Kg produced an antinociceptive effect. Bestatin (400 µg/paw), a selective aminopeptidase-N inhibitor, potentiates the intermediate analgesic response of CBD at the dose of 2 mg/Kg. Naloxone (50 µg/paw), a non-selective opioid receptor antagonist, reversed the CBD-mediated analgesia. CTOP (5, 10, and 20 µg/paw) and naltrindole (30, 60, and 120 µg/paw), μ and Δ opioid receptor antagonists, but not norBNI (200 µg/paw), a κ opioid receptor antagonist, partially reversed the CBD analgesia. Thus, our study shows that cannabidiol may induce activation of opioid receptors in the periphery as a part of its analgesic mechanism in neuropathic pain.
Relationship between prefrontal oxygenation during task-set period and executive function in healthy older people: A near-infrared spectroscopy study.
Oboshi Y, Kikuchi M, Ouchi Y
Neurosci Lett · 2025 Nov · PMID 41022277 · Publisher ↗
INTRODUCTION: In past research, we have examined the characteristics of brain activity caused by prefrontal task completion in healthy older adults in a simplified manner using a near-infrared spectroscopy device, with t...
INTRODUCTION: In past research, we have examined the characteristics of brain activity caused by prefrontal task completion in healthy older adults in a simplified manner using a near-infrared spectroscopy device, with the aim of identifying methods of early intervention to prevent their cognitive decline. Previously, we reported that prefrontal oxygenation during pre-task preparation was greater in young adults than older adults, and that this greater activation was associated with better task performances in both groups. To extend this research, in the present study, we examined previous findings with task repetitions, as older adults take more time to become familiar new tasks. METHODS: We modified the working memory task with a clear task-set instruction and examined the change in the task-set and task-induced activation in 63 cognitively healthy older adults. RESULTS: Task-set activation did not increase even after three repetitions, and the task-induced activation was greater than task-set activation in most channels. The difference in degree between task-induced activation and task-set activation showed a reduction with task repetitions. Significant inverse correlations were observed between the prefrontal activation due to the task itself in the third session, i.e., after task repetitions and the reaction time of the Trail Making Test, which represents attentional function. DISCUSSION: These results indicate that continued activation by the task itself, which persists even after older adults become familiar with the task, may be associated with executive function decline.
Nicotine exacerbates fear and depression-like behaviors by promoting microglial phagocytosis of synaptic protein in a mouse model of foot shock.
Wang J, Gong XK, Yu J … +7 more , Wu L, Zhang Y, Li P, Qin M, Wang XC, Shu XJ, Bao J
Neurosci Lett · 2025 Nov · PMID 41015226 · Publisher ↗
Post-traumatic stress disorder (PTSD) is a severe psychiatric disorder characterized by a complex interplay of genetic and environmental influences. Substantial evidence has demonstrated an intricate nexus between nicoti...
Post-traumatic stress disorder (PTSD) is a severe psychiatric disorder characterized by a complex interplay of genetic and environmental influences. Substantial evidence has demonstrated an intricate nexus between nicotine, the principal psychoactive constituent of cigarette smoke, and PTSD neuropathology. Nevertheless, the intricate mechanism underlying the relationship between nicotine consumption and PTSD has not yet been fully understood. Following two weeks of intraperitoneal nicotine administration at two doses (5 mg/kg and 1 mg/kg), we initiated behavioral testing. Our findings reveal that nicotine supplementation exacerbates fear and depression-like behaviors while promoting microglial phagocytosis of synaptic proteins. Moreover, we observed synaptic protein loss and microglial activation in both the hippocampus and cortex in the 5 mg/kg group. CX3CR1-Cre driven Cre recombinase (Cre) is a widely used genetic tool for enabling gene manipulation in microglia. Here, we investigated a genetic ablation method of the CX3CR1 using a Cre-responsive adeno-associated virus (AAV) vector expressing diphtheria toxin subunit-A (DTA). Conversely, microglial ablation via rAAV-EF1a-DIO-DTA-WPRE hGH pA injection in the ventral hippocampus CA1 region of CX3CR1-Cre mice appears to mitigate the pathologies and behavioral abnormalities induced by nicotine. Our results underscore the role of nicotine in the progression of PTSD and demonstrate that microglial depletion mitigates nicotine-induced pathologies and behavioral disturbances. Consequently, our findings suggest that nicotine enhances microglial phagocytosis of synaptic proteins in PTSD, thereby exacerbating fear and depressive symptoms.
Short-term effects of sertraline against depressive-like behaviors in a rat model of neonatal hypoxic encephalopathy.
Serghani MM, Kassem-Moussa S, Makki R … +12 more , Kurdi A, Elbaset M, Hajjar H, Jammal RE, Flath-Everhard GT, Prasad I, Eid A, Habib A, Hamade E, White FA, Badran B, Obeid M
Neurosci Lett · 2025 Nov · PMID 41005612 · Publisher ↗
Hypoxic encephalopathy of the newborn is associated with long-term neurodevelopmental behavioral deficits that lack a definitive "optimal" treatment approach. We previously demonstrated that periadolescent depressive-lik...
Hypoxic encephalopathy of the newborn is associated with long-term neurodevelopmental behavioral deficits that lack a definitive "optimal" treatment approach. We previously demonstrated that periadolescent depressive-like behaviors occur in a rat model of early-life hypoxia. Here, we investigated the short-term effects of the selective serotonin reuptake inhibitor, sertraline, against later-life behavioral deficits. Rats were exposed to global hypoxia at postnatal day 10 (P10) and then received either sertraline or its vehicle (P24 to P30). Normoxic controls received sertraline or its vehicle. Depressive-like and anxiety-like behaviors were assessed using the forced swim test (FST) and open field test (OFT), respectively. The FST was conducted at P25-26 and the OFT at P27. Rats were sacrificed at P30 to assess hippocampal microRNA (miR) expression and to histologically evaluate hippocampal neuronal densities and synaptophysin (Syp) protein levels. Early-life hypoxic seizures resulted in increased immobility in the FST (p < 0.05) and decreased exploration in the OFT (p < 0.05). Hypoxia also resulted in chronic alterations in the expression of 25 miRs, 22 of which are known to modulate inflammatory responses and synaptic function. Sertraline treatment normalized hypoxia-induced increased immobility and reversed 17 out of 25 alterations in miR expression. However, sertraline potentiated hypoxia-induced exploratory deficits (p < 0.05). The drug treatment also resulted in OFT deficits in controls (p < 0.05) and 13 unique dysregulations in miR expression. Neuronal densities and Syp levels were comparable among all groups. We demonstrate that sertraline reverses hypoxia-induced depressive-like behaviors, possibly by targeting inflammation and synaptic remodeling. Sertraline-induced anxiety-like behaviors may reflect its known transient early side effects and warrant further research on long-term outcomes.
Tanshinone IIA and hydroxy safflower yellow A reduce cerebral injury via TLR4/NF-κB pathway in rats.
Luo B, Zheng Y, Miao Q … +8 more , Zhang Y, Lei Y, Xu Q, Li W, Yu J, Zhu X, Yuan J, Zhu H
Neurosci Lett · 2025 Nov · PMID 40992457 · Publisher ↗
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 CIR...
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.
Blockade of acid-sensing ion channels 1a in the mice dorsal raphe nucleus inhibits panic-like responses: Role of 5-HT receptors in the dorsal periaqueductal gray.
Frias AT, Hernandes PM, Zangrossi H
Neurosci Lett · 2025 Nov · PMID 40992456 · Publisher ↗
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. Acid-sensing ion channels (ASIC...
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. 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. 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 receptor antagonist. Our study provides novel evidence that ASIC1a channels in the lwDRN contribute to CO-evoked escape responses and that this modulation depends on serotonergic signaling via 5-HT 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.
Vitamin D alleviates AD-like pathology in APP/PS1 mice by inhibiting pyroptosis and neuroinflammation via DJ-1/PARK7.
Zhou C, Wang Y, Zuo L … +5 more , Miao Y, Li W, Li X, Xue Y, Li M
Neurosci Lett · 2025 Nov · PMID 40987383 · Publisher ↗
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 an...
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 VD (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 VD significantly ameliorated cognitive deficits and attenuated AD-like pathology in APP/PS1 mice. Moreover, VD 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-induced improvements in neuroinflammation and neuronal pyroptosis, implicating that DJ-1 is a crucial modulator in the effects of VD on Alzheimer's disease pathology.
Mini-Review: Cathodal tDCS over the right prefrontal cortex and inhibitory control: Pinpointing an electrode montage to disrupt a domain-general system.
Gómez-Ariza CJ, Pacios J
Neurosci Lett · 2025 Nov · PMID 40987382 · Publisher ↗
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 cont...
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.
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.
Li Y, Zhang C, Han L … +1 more , Qian Z
Neurosci Lett · 2025 Nov · PMID 40983134 · Publisher ↗
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 ai...
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.
COPII component Sec13 is required for peripheral myelination and Schwann cell maintenance.
Wu D, Li Z, Lu X … +4 more , Li L, Dai W, Wang X, Zhang L
Neurosci Lett · 2025 Nov · PMID 40972809 · Publisher ↗
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...
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.
Acute restraint stress and epinephrine administration disrupt cognitive and emotional functions in male rats via modulation of proinflammatory cytokines, MCT-2, and neurogranin.
Sezgin Z, Ozacmak HS, Turan I
Neurosci Lett · 2025 Nov · PMID 40930456 · Publisher ↗
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 lear...
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.
Repetitive transcranial magnetic stimulation alleviates radiation-induced brain injury in rats: involving the inhibition of ferroptosis.
Wei XX, Liu HJ, Liao ZZ … +5 more , Li XX, Ma LL, Zou W, Zhou GJ, Tang XQ
Neurosci Lett · 2025 Nov · PMID 40925463 · Publisher ↗
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 rece...
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.
1, 2, 4-trimethoxybenzene alleviates pain and related psychiatric disorders by inhibiting NLRP3 inflammasome activation.
Kong X, Fan Z, Rui T … +6 more , Qi Y, Wang X, Zhang A, Chen X, Liao Y, Ma J
Neurosci Lett · 2025 Oct · PMID 40915345 · Publisher ↗
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...
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) 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.
Learning from a novel "Tutor" Uncouples song imitation and preference in zebra finches.
Tarnaski HO, Cheung A, Frank SY … +3 more , Hunt JL, Tang C, Gobes SMH
Neurosci Lett · 2025 Oct · PMID 40912353 · Publisher ↗
Neuroscientists commonly use behavior to assess the impact of experimental neural manipulations. While novel technical methods need to be carefully controlled for unintended effects, the use of behavioral metrics without...
Neuroscientists commonly use behavior to assess the impact of experimental neural manipulations. While novel technical methods need to be carefully controlled for unintended effects, the use of behavioral metrics without consideration of normal development should be approached with caution as well. In zebra finches, song imitation and song preference are behavioral indicators of memory that are learned interdependently from the father under standard laboratory conditions. Here, we manipulate the natural learning environment by introducing a novel "tutor" for brief tutoring sessions mid-development, a paradigm frequently used simultaneously with neural manipulations. By using song-preference tests and three distinct methods to quantify song imitation, we reveal that behavioral plasticity can occur independently in these two domains. While song preference and imitation are usually learned together, our results indicate a neural dissociation between these two forms of learning and memory upon introduction of a novel song tutor. This highlights the importance of critically evaluating the validity of behavioral paradigms when inferring neural function from experimental manipulations.
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