Neurosci. Lett. [JOURNAL]
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200 papers
Short-term immobilization impairs pointing direction programming and early motor control processes.
Scotto CR, Danion FR, Blandin Y … +1 more , Toussaint L
Neurosci Lett · 2026 Jan · PMID 41232746 · Publisher ↗
Short-term limb immobilization is a valuable method for studying the contribution of proprioception since it temporarily reduces sensory and motor inputs. While several studies have shown that immobilization impairs cogn...
Short-term limb immobilization is a valuable method for studying the contribution of proprioception since it temporarily reduces sensory and motor inputs. While several studies have shown that immobilization impairs cognitive and sensorimotor processes, none have yet demonstrated how it could specifically impact the programming of movement direction. Here, participants (N = 32) made uncorrected pointing movements toward five visual targets located in different directions - but requiring constant amplitude - without benefiting from any visual feedback on the hand. Pointing was performed on two consecutive days by Control and Immobilized participants, the latter of whom had worn a splint on the right arm during this 24 h period. Results showed that immobilization increased the duration of movement planning (i.e., longer reaction time) necessary to specify hand-path direction. A greater counterclockwise directional bias was observed at peak acceleration in the Immobilized group and persisted until the uncorrected movement offset. These results suggest that immobilization impacts direction programming as well as early motor control processes. We argue that proprioception deprivation impairs the perception of limb position, leading to both slower and less accurate motor command selection. Overall, we interpret that the lack of proprioceptive feedback and efference copies may influence the accuracy of movement planning after 24 h of immobilization, possibly reflecting changes in processes related to internal model mechanisms.
Limited effects of the REV-ERB agonist SR9009 after mouse spinal cord contusion: Reduced acute pathology with unaffected functional recovery and chronic white matter loss.
Slomnicki LP, Hodges E, Armstrong C … +5 more , Morehouse J, Burke D, Ohri SS, Burris TP, Hetman M
Neurosci Lett · 2026 Jan · PMID 41232745 · Full text
The ligand-regulated transcription factors REV-ERBα/NR1D1 and REV-ERBβ/NR1D2 are promising neuroprotective targets. Systemic administration of the REV-ERB agonist SR9009 has been shown to reduce neuroinflammation, limit...
The ligand-regulated transcription factors REV-ERBα/NR1D1 and REV-ERBβ/NR1D2 are promising neuroprotective targets. Systemic administration of the REV-ERB agonist SR9009 has been shown to reduce neuroinflammation, limit tissue loss, and enhance functional recovery in several models of acute CNS injury. To evaluate its potential in spinal cord injury (SCI), a moderate contusion was induced at the T9 level in mice. SR9009 was administered intraperitoneally at 100 mg/kg per day (two 50 mg/kg doses at ZT1 and ZT12) for the first 7 days post-injury, when tissue damage is most pronounced in this model. At 3 days post-SCI, SR9009-treated mice exhibited reduced hematoma and decreased expression of transcripts associated with blood-spinal cord barrier disruption, inflammation, and cellular stress responses. However, hindlimb functional recovery remained unchanged throughout 6 weeks of follow-up, and no significant differences in white matter sparing were observed at study completion. These findings indicate that although SR9009 reduces acute activation of some secondary injury cascades, it does not promote long-term tissue preservation or functional recovery after contusive SCI in mice.
Expression of serotonin transporter (SERT) and receptors 5-HTR1A and 5-HTR2A in an animal model of hypothermia.
Negoiţă A, Amuzescu B, Mihăilescu DF … +2 more , Banciu DD, Banciu A
Neurosci Lett · 2026 Jan · PMID 41232744 · Publisher ↗
The role of anterior hypothalamus and preoptic area in thermoregulation has been studied since the late 19 century (Charles Richet 1884, Aronsohn&Sachs 1885), and thermosensitive neurons have been recorded in these areas...
The role of anterior hypothalamus and preoptic area in thermoregulation has been studied since the late 19 century (Charles Richet 1884, Aronsohn&Sachs 1885), and thermosensitive neurons have been recorded in these areas. Numerous animal studies with injection of serotonergic agonists or antagonists proved activation of thermoregulatory responses, and complex serotonergic circuits with origin in dorsal raphe nucleus (DRN) and projection in hypothalamus and preoptic area (POA), nucleus accumbens (Acc), and central amygdala were identified. We assessed the expression of serotonin transporter SERT, 5-HT1A and 5-HT2A receptors at mRNA and protein level in several brain regions: brainstem raphe, hypothalamus, Acc and POA, amygdala, piriform cortex (Pir) in adult male CD1 mice kept 4 h/day at 4 °C or normal temperature (control) for 1-2 months. For qRT-PCR total RNA was extracted from fresh samples with a GenElute™ kit (Sigma), followed by RT and qPCR with hydrolysis probes (Applied Biosystems). For immunofluorescence 200 µm slices were cut from fixed brains and stained with primary antibodies ASR-021, ASR-033, AMT-004 (Alomone Labs) and secondary antibody N2404-Ab635P-L (NanoTag), co-stained with phalloidin-AlexaFluor488 and DAPI. We obtained statistically significant (two-tailed t test) increases in mRNA expression in hypothermia vs. control for SERT and 5-HT2A in the brainstem raphe and hypothalamus. Fluorescence intensities (averaged over small relevant regions and normalized to DAPI fluorescence) were higher in hypothermia for the two receptors in DRN and Acc, and similar to control levels in Pir and amygdala, proving activation of central serotonergic thermoregulatory circuits.
Immunohistochemically-detected differential localization of CXCL14 in mouse cerebellum suggesting the presence of neuronal and glial forms of CXCL14.
Suzuki H, Yamamoto T, Hasegawa A … +5 more , Tamaki T, Komagata JY, Yamaga T, Akasaka T, Hata RI
Neurosci Lett · 2026 Jan · PMID 41207553 · Publisher ↗
In this study we compared staining profiles in mouse cerebellum, using two anti-CXCL14 antibodies, which we designated α and β. The α anti-CXCL14 antibody labeled Purkinje neurons; this was confirmed by double-immunofluo...
In this study we compared staining profiles in mouse cerebellum, using two anti-CXCL14 antibodies, which we designated α and β. The α anti-CXCL14 antibody labeled Purkinje neurons; this was confirmed by double-immunofluorescence staining with calbindin D-28k, a marker for Purkinje neurons. The β anti-CXCL14 antibody marked Bergmann glia; this was confirmed by combinational staining with glial fibrillary acidic protein, a marker for Bergmann glia. Both staining profiles were abolished by preabsorption of each antibody with recombinant human CXCL14. Western blot analyses using these two antibodies indicated that they both recognized recombinant human and mouse CXCL14s, which migrated at approximately a 12 kDa position. Furthermore, the α anti-CXCL14 antibody labeled major bands at approximately 15 kDa and 21 kDa, and a minor band at approximately 19 kDa from a Triton-X fraction of mouse cerebellum. However, there were no immunostaining bands from a Tris-HCl fraction. In contrast, the β anti-CXCL14 antibody labeled a band of approximately 18 kDa from a Tris-HCl fraction of cerebellum, but no immunoreactive bands were detected from a Triton-X fraction. These results suggest that mouse cerebellum has at least two forms of CXCL14; presumably a neuronal form and a glial form.
Sensory afferents in the mammary papilla are eliminated during the lactation.
Nakayama K, Suzuki K, Marunaka Y … +5 more , Kondo M, Yokouchi Y, Takeda N, Yamamura K, Hasegawa H
Neurosci Lett · 2026 Jan · PMID 41192539 · Publisher ↗
Importance of breastfeeding is well recognized, since it supports the survival of mammalian infants. The mammary papilla, a specialized skin region for breastfeeding, acts as a vital interface between mother and infant:...
Importance of breastfeeding is well recognized, since it supports the survival of mammalian infants. The mammary papilla, a specialized skin region for breastfeeding, acts as a vital interface between mother and infant: perceiving the suckling to trigger the milk ejection reflex in mother and transporting milk from mother to infants. Despite its crucial roles in breastfeeding, the histological and cellular changes in the mammary papilla during lactation remain poorly understood. In this study, we focused on the sensory afferent projection mediating somatosensory perception. Our observation revealed that the mammary papilla is innervated by non-peptidergic C-fibers, which engage in the mechanical nociception. Moreover, we found that these sensory afferents are eliminated in the mammary papilla of lactating females. These results propose the lactation-associated elimination of sensory afferents in the mammary papilla as a novel mechanism adaptive for the breastfeeding.
Involvement of CXCR2 in chronic postsurgical pain occurrence through ERK/p38 activation.
Ge T, Chen X, Liu C … +1 more , Huang S
Neurosci Lett · 2026 Jan · PMID 41192538 · Publisher ↗
Chronic postsurgical pain (CPSP) is a global concern associated with significant health and economic issues for patients. We investigated the effects of C-X-C motif chemokine receptor 2 (CXCR2) related signal transductio...
Chronic postsurgical pain (CPSP) is a global concern associated with significant health and economic issues for patients. We investigated the effects of C-X-C motif chemokine receptor 2 (CXCR2) related signal transduction mechanisms on CPSP in a rat skin muscle incision and retraction (SMIR) model. Following model establishment, glial cells in the spinal dorsal horn were activated, and the expression of inflammatory factors (tumor necrosis factor (TNF)-α and interleukin (IL)-1β increased. The SMIR group demonstrated elevated expression of CXCR2, phosphorylated ERK (p-ERK), and phosphorylated p38 (p-p38) in the spinal dorsal horn. After intrathecal injection of the CXCR2 antagonist SB225002, the rats' pain threshold increased, accompanied by reduced expression of inflammatory factors and reversal of glial cell activation. Additionally, primary microglial cells induced by lipopolysaccharide were used as an in vitro model. Transfection with si-CXCR2 led to decreased expression of p-ERK and p-p38 in microglial cells, along with lower TNF-α and IL-1β levels in the cell supernatant. These results indicate that CXCR2 activates spinal glial cells via the ERK/p38 pathway, promoting neuroinflammation, and CPSP, whereas CXCR2 inhibition counteracts these effects and alleviates CPSP.
Stress-type specific changes of VIP signaling in limbic regions of the rat brain.
Ferro F, Fontebasso V, Basille-Dugay M … +2 more , Vaudry D, Ebner K
Neurosci Lett · 2026 Jan · PMID 41177440 · Publisher ↗
Vasoactive intestinal peptide (VIP) is a highly abundant neuropeptide in the central nervous system, implicated in the regulation of numerous behavioral and physiological functions, including the central stress response....
Vasoactive intestinal peptide (VIP) is a highly abundant neuropeptide in the central nervous system, implicated in the regulation of numerous behavioral and physiological functions, including the central stress response. Notably, VIP and its cognate receptors, VPAC1 and VPAC2, are widely expressed in brain areas implicated in stress and anxiety regulation such as the amygdala. However, the exact role of VIP in stress function is not fully understood. The present study therefore examined how acute or chronic stress affect VIP and VPAC receptor gene expression in specific limbic brain regions of Sprague-Dawley rats using quantitative real-time PCR. Acute stress via forced swim exposure significantly increased VIP expression in the central amygdala (CeA) by 200 %, and in the medial amygdala (MeA) by 350 %. It also elevated VPAC1 receptor expression in the hypothalamic paraventricular nucleus (PVN), basolateral amygdala (BLA), and CeA, and VPAC2 receptor expression in the bed nucleus of the stria terminalis (BNST) and BLA. Chronic unpredictable stress induced both overlapping and distinct patterns, including upregulation of the VPAC1 receptor expression in the PVN by 120 % and the VPAC2 receptor in the CeA by 280 %, accompanied by slight downregulation of VIP in the CeA. These findings highlight a stress-duration-dependent and region-specific regulation of the VIP/VPAC receptor system and its potential role in modulating stress-related neural circuits.
Neuro-protection of swertisin against impairment induced by Aβ by acting on COX-2 to up-regulate 2-AG and suppressing neuroinflammation.
Wu J, Zhou L, Lang C
Neurosci Lett · 2026 Jan · PMID 41167584 · Publisher ↗
Ziziphi Spinosae Semen (Suan Zao Ren) is a traditional Chinese medicine with the functions of nourishing the heart and liver, calming the mind, and stopping sweating. Swertisin, one of the main active ingredients in Zizi...
Ziziphi Spinosae Semen (Suan Zao Ren) is a traditional Chinese medicine with the functions of nourishing the heart and liver, calming the mind, and stopping sweating. Swertisin, one of the main active ingredients in Ziziphi Spinosae Semen, has a wide range of pharmacological effects such as anti-inflammation, anti-oxidation, and enhancement of learning and memory. Based on the Aβ cascade and the neuroinflammatory theory, combined with the anti-inflammatory neuroprotective effect of endocannabinoid 2-AG, this work integrated modern biochemical technology methods such as liquid chromatography-mass spectrometry, Western blot, and electrophysiological technique to explore the neuroprotective effects and potential mechanism of swertisin on the Alzheimer's disease (AD) model induced by Aβ. The results showed that swertisin relieved impairment of learning and memory caused by Aβ on hippocampus slice by decreasing COX-2 expression and inhibiting COX-2 activity to up-regulate the endogenous 2-AG, and suppressing neuroinflammation and neuronal apoptosis via CB1R-dependent NF-κB pathway. It was further discovered that swertisin protected the primary hippocampal neurons, reduced over-expression of COX-2, and relieved the neuroinflammatory against Aβ through the CB1R-dependent NF-κB signaling pathway. Finally, it was confirmed that swertisin alleviated BV-2 cell apoptosis induced by Aβ These results help us understand the mechanism of swertisin against AD and promote the development of related drugs and healthy products.
Acute exposure to vaporized cannabidiol remodels coding and noncoding transcriptomes in the mouse striatum.
Choi MR, Park C, Kim J … +5 more , Heo JH, Chang SH, Kim HN, Jin YB, Lee SR
Neurosci Lett · 2025 Dec · PMID 41151688 · Publisher ↗
Cannabidiol (CBD) is increasingly consumed via vaping, but its acute molecular impact on the striatum, a critical hub for motor control and reward processing that is highly sensitive to cannabinoid modulation, remains po...
Cannabidiol (CBD) is increasingly consumed via vaping, but its acute molecular impact on the striatum, a critical hub for motor control and reward processing that is highly sensitive to cannabinoid modulation, remains poorly understood. This study investigated differential expression of long noncoding RNAs (lncRNAs) and mRNAs in the striatum after acute exposure to vaporized CBD. Male ICR mice (n = 5 per group) were exposed to vaporized CBD oil (50 mg) and striatal tissues were collected 24 h later. Differentially expressed mRNAs and lncRNAs were identified using total RNA sequencing and mRNA-lncRNA co-expression networks were constructed. Selected transcripts were validated using qRT-PCR and discriminative capacity was assessed by ROC analysis. CBD exposure altered the expression of 931 mRNAs and 229 lncRNAs. GO and KEGG analyses revealed bidirectional regulation of pathways involved in neural development and synaptic transmission, including both up- and downregulated genes in categories such as glutamatergic synapse. Ion transport genes (Trpm2, Tmem63a, Tmem175, Glrb) were robustly upregulated, while genes involved in excitatory synaptic structure (Dlgap2, Shisa9, Tac1) and dopaminergic-associated pathways (Drd3, Oxt) were downregulated. mRNA-lncRNA network analysis highlighted regulatory hubs including NONMMUT114016.1 and NONMMUT057055.2, and ROC analysis identified strong biomarker candidates such as Tmem175, Ptprd, NONMMUT042895.2, and NONMMUT151847.1. These findings indicate that acute CBD vaping induces widespread transcriptomic remodeling in the striatum, enhancing ion transport and inhibitory signaling while suppressing excitatory and dopaminergic pathways. This study provides the first comprehensive striatal transcriptome profiling of coding and noncoding RNAs in response to vaporized CBD.
Site-Specific Regulation of Tau phosphorylation by MAPK pathways during HFS-Induced synaptic plasticity in the Rat hippocampus.
Süer C, Tan B, Dursun N … +2 more , Koşar B, Babur E
Neurosci Lett · 2025 Dec · PMID 41130560 · Publisher ↗
This study examined the role of MAPKs in Tau phosphorylation and synaptic plasticity at perforant pathway-dentate gyrus (PP-DG) synapses following high-frequency stimulation (HFS). In vivo experiments were conducted on a...
This study examined the role of MAPKs in Tau phosphorylation and synaptic plasticity at perforant pathway-dentate gyrus (PP-DG) synapses following high-frequency stimulation (HFS). In vivo experiments were conducted on adult male Wistar rats under urethane anesthesia. Field potentials (fEPSP and PS) were recorded in the DG granule cell layer in response to PP stimulation. Western blotting assessed total and phosphorylated levels of Tau, ERK1/2, JNK, and P38 MAPK in HFS-induced hippocampus. MAPK inhibition disrupted early somatic potentiation when applied during induction, and JNK inhibition alone impaired late potentiation. Reduced somatic activity correlated with decreased MAPK phosphorylation and Tau phosphorylation at Ser422. Findings suggest that ERK1/2, JNK, and P38 are essential for Tau phosphorylation at Ser422 in HFS-induced hippocampal synapses.
From stress to Alzheimer's: A circuit-based framework for prefrontal cognitive dysfunction.
Yi JH
Neurosci Lett · 2025 Dec · PMID 41115499 · Publisher ↗
Impairments in working memory and cognitive flexibility are early and consistent features of both Alzheimer's disease (AD) and stress. These functions depend critically on prefrontal cortical (PFC) circuits, which are pa...
Impairments in working memory and cognitive flexibility are early and consistent features of both Alzheimer's disease (AD) and stress. These functions depend critically on prefrontal cortical (PFC) circuits, which are particularly vulnerable to neuromodulatory and pathological insults. Recent studies suggest that stress and AD do not simply act globally, but instead converge on specific molecular and cellular targets within distinct neural populations. Notably, both chronic stress and Alzheimer's disease models exhibit dysregulation of synaptic signaling via NR2B-containing NMDA receptors and aberrant GSK-3β activation. These changes often emerge in a cell-type-specific manner, affecting excitatory pyramidal neurons and vulnerable interneuron subtypes such as SST+, PV+, and VIP + cells. The resulting imbalance in excitation and inhibition disrupts the integrity of prefrontal circuits, impairing adaptive behavior. This review synthesizes evidence across molecular, cellular, and circuit levels to outline a framework in which stress and AD pathology converge on shared vulnerable pathways. Understanding how specific cell populations mediate this vulnerability may lead to targeted strategies for enhancing cognitive resilience in neurodegenerative and stress-related disorders.
Mini-review: "Hippocalcin: Molecular mechanisms and therapeutic potential in neuronal function".
Park SY
Neurosci Lett · 2025 Dec · PMID 41115498 · Publisher ↗
Hippocalcin (HPCA), a neuronal Ca sensor protein in the EF-hand superfamily, plays a key role in calcium signaling and neurological function in the central nervous system. This review highlights HPCA's structure-function...
Hippocalcin (HPCA), a neuronal Ca sensor protein in the EF-hand superfamily, plays a key role in calcium signaling and neurological function in the central nervous system. This review highlights HPCA's structure-function relationships and clinical significance. Through Ca2-dependent conformational changes and a unique calcium-myristoyl switch, HPCA dynamically associates with membranes, acting as both sensor and effector. It modulates neuronal excitability, synaptic plasticity, neurodevelopment, and neuroprotection. Notably, HPCA is critical in mediating slow afterhyperpolarization, a key mechanism for adjusting neuronal firing patterns and maintaining excitability homeostasis. It also influences neural stem cell fate by promoting neuronal differentiation and suppressing astrocytic differentiation. HPCA maintains mitochondrial calcium homeostasis and activates survival pathways, protecting against apoptosis and oxidative stress. Its dysregulation is implicated in Alzheimer's and Parkinson's diseases, epilepsy, depression, schizophrenia, and dystonia. Given its restricted expression in the brain and multifaceted functional roles, further elucidation of HPCA-mediated signaling mechanisms is warranted to advance the development of targeted therapeutic strategies for a broad spectrum of neurological disorders.
Limitations of antibody-mediated neutrophil depletion in understanding the role of neutrophils following spinal cord injury in mice.
Zhou R, Song D, Li M … +1 more , Gao H
Neurosci Lett · 2025 Dec · PMID 41110756 · Publisher ↗
The role of neutrophils in spinal cord injury (SCI) remains incompletely understood due to the absence of effective intervention strategies. Some studies employing antibody-mediated neutrophil depletion (ND) in vivo have...
The role of neutrophils in spinal cord injury (SCI) remains incompletely understood due to the absence of effective intervention strategies. Some studies employing antibody-mediated neutrophil depletion (ND) in vivo have yielded various conclusions. However, the mechanism of ND remains unclear, and a comprehensive assessment of its effects was largely lacking prior to application. In this study, we aimed to evaluate neutrophil-related changes following ND in SCI. Hematological analysis revealed that ND attenuated the SCI-induced rise in neutrophil counts but had a negligible effect on baseline levels. The level of IL-1β and IL-8 increased in plasma and intact spinal cord after ND, but exhibited divergent changes post-SCI. Tissue concentrations of TNF-α were elevated in the intact spinal cord but declined following SCI with ND. Neutrophil elastase, a neutrophil cytoplasm-specific protein, increased in both intact and injured spinal cord following ND. Furthermore, ND did not markedly affect SCI-induced blood-spinal cord barrier (BSCB) leakage. These findings indicate that antibody-mediated ND produces complicated effects, rendering it a suboptimal approach for studying neutrophils' contributions in SCI pathophysiology. Conclusions derived from this method should be interpreted with caution, and alternative strategies should be pursued to better elucidate the role of neutrophils in SCI.
Ferulic acid possesses anxiolytic activity: evidence for the involvement of serotonergic and noradrenergic systems.
Cetiner OP, Eken H, Alyu Altınok F … +2 more , Arslan R, Bektas N
Neurosci Lett · 2025 Dec · PMID 41086980 · Publisher ↗
The current study aims to evaluate any potential anxiolytic effects and the action mechanisms of ferulic acid, a phenolic phytochemical compound, in mice. The anxiolytic activity of ferulic acid at the doses of 0.1, 1, 1...
The current study aims to evaluate any potential anxiolytic effects and the action mechanisms of ferulic acid, a phenolic phytochemical compound, in mice. The anxiolytic activity of ferulic acid at the doses of 0.1, 1, 10, and 100 mg/kg, p.o in female BALB/c mice was assessed by open field, hole-board and elevated plus maze tests. The possible roles of noradrenergic, serotonergic, and GABAergic modulation in the anxiolytic action of 100 mg/kg ferulic acid were also investigated by pretreatment with 5 mg/kg (i.p.) yohimbine, 1 mg/kg (i.p.) WAY-100635, and 3 mg/kg (i.p.) flumazenil, respectively, in the hole-board and open field tests. Similar to the positive standard diazepam (1 mg/kg, i.p); without altering the locomotor activity, 100 mg/kg ferulic acid significantly altered all the parameters related to anxiolytic activity, whereas 0.1 and 10 mg/kg doses were found to be effective in only some parameters in elevated plus-maze and open field tests, suggesting a U-shaped dose-response pattern. The anxiolytic effect of 100 mg/kg ferulic acid was significantly antagonized by the pretreatment with 5-HT receptor antagonist WAY-100635 and especially by α-2 adrenoceptor antagonist yohimbine while the anxiolytic action was not blocked by GABA/BZ receptor antagonist flumazenil pretreatment. The findings imply that ferulic acid's anxiolytic effect is mediated by the activation of α-2 adrenoceptors and 5-HT receptors. In conclusion, it is possible to say that ferulic acid can be a safe potential agent which that be used alone or in combination with current effective treatments for anxiety.
Insulin-regulated aminopeptidase inhibitor C9 restores cellular activity in methadone-damaged primary cell cultures.
Stam F, Bjurling S, Nylander E … +6 more , Håkansson EO, Gising J, Larhed M, Odell LR, Grönbladh A, Hallberg M
Neurosci Lett · 2025 Dec · PMID 41077171 · Publisher ↗
Insulin-regulated aminopeptidase (IRAP) is emerging as a pharmaceutical target for treatment of neurotoxic- and neurodegenerative symptoms commonly seen in cognitive impairments. Ligands of IRAP, such as Angiotensin IV a...
Insulin-regulated aminopeptidase (IRAP) is emerging as a pharmaceutical target for treatment of neurotoxic- and neurodegenerative symptoms commonly seen in cognitive impairments. Ligands of IRAP, such as Angiotensin IV and similar analogues, bind to the active site of IRAP and causes an inhibition of its enzymatic activity, which is suggested to improve cognitive functions. Opioids are widely used in the clinic to treat for example pain and opioid use disorder, however opioid use have been associated with cognitive impairments, impaired neuronal development, and neuronal damage. To evaluate the potential of the macrocyclic IRAP inhibitor compound 9 (C9), the present study examined the restorative effects of C9 after opioid-induced cell toxicity. The toxic impact of the commonly used opioids methadone and buprenorphine was determined in rat primary hippocampal and cortical cells, along with the effects on various viability markers after subsequent treatment with C9. The metabolism of tetrazolium bromide salt (MTT) was measured to assess mitochondrial activity, and the level of membrane damage was assessed by measuring lactate dehydrogenase (LDH) in the cell media. Fluorescent calcein dye was used to evaluate intracellular esterase activity. In conclusion, this study demonstrate that methadone and buprenorphine induce toxic effects in primary hippocampal and cortical cell cultures and that IRAP inhibitor C9 has a restorative effect on intracellular esterase activity in methadone-damaged cells.
Differential expression of TRPV1 and TRPM8 in the mouse trigeminal ganglion and spinal dorsal root ganglion.
Shao C, Wei J, Jia HY … +4 more , Zhou YH, Zhao M, Yang K, Zhang MM
Neurosci Lett · 2025 Nov · PMID 41077170 · Publisher ↗
Transient receptor potential (TRP) ion channels, including the thermoreceptor TRP vanilloid 1 (TRPV1) and innocuous warm detector TRP melastatin 8 (TRPM8), are widely expressed on the primary sensory neurons of the trige...
Transient receptor potential (TRP) ion channels, including the thermoreceptor TRP vanilloid 1 (TRPV1) and innocuous warm detector TRP melastatin 8 (TRPM8), are widely expressed on the primary sensory neurons of the trigeminal ganglion (TG) and the dorsal root ganglion (DRG). By performing real-time quantitative PCR and immunostaining, we compared TRPV1 and TRPM8 gene expression and immunostaining in mouse DRG and TG neurons. Both TRPV1 and TRPM8 are widely expressed in the TG and DRG, but in different patterns: TRPV1 has relatively more abundant expression and immunostaining in the DRG, whereas TRPM8 has higher levels in the TG. Double-staining for TRPV1 and TRPM8 revealed very little coexpression in either the TG or the DRG. These results suggest that TRPV1 and TRPM8 are differentially expressed in TG and DRG, and this significant variation may underlie the different temperature sensory properties of the skin and oral cavity.
Stable Traits, Adaptive Brains: links between Visual Homeostatic Plasticity and Personality.
Baroni M, Cesari V, Gemignani A … +3 more , Morrone MC, Lunghi C, Menicucci D
Neurosci Lett · 2025 Nov · PMID 41077169 · Publisher ↗
This study explores the relationship between personality traits and visual homeostatic plasticity, a neural mechanism maintaining stable the brain activity. Actually, personality may influence neuroplasticity, the genera...
This study explores the relationship between personality traits and visual homeostatic plasticity, a neural mechanism maintaining stable the brain activity. Actually, personality may influence neuroplasticity, the general brain ability to adapt through experiences. Indeed, prior research links traits like openness to experience and neuroticism to Hebbian plasticity (experience-based synaptic strengthening), but any connections to homeostatic plasticity remain largely unexplored. To probe homeostatic plasticity we tested the effect of short-term monocular deprivation in 24 healthy adults. Participants wore an eye patch for two hours, and underwent binocular rivalry tests measuring shifts in perceptual dominance. The deprivation index, reflecting homeostatic plasticity in the primary visual cortex, was analysed alongside personality traits assessed via the Big Five Questionnaire. Results revealed a positive correlation between the deprivation index and conscientiousness but a negative correlation with emotional stability. Conscientious individuals, often goal-directed and self-regulated, showed reduced homeostatic plasticity, suggesting diminished mental flexibility. Conversely, higher emotional stability (lower neuroticism) enhanced homeostatic plasticity, aligning with findings that neuroticism reduces resilience, a potential link to impaired plasticity. Overall, the study suggests that homeostatic plasticity, often limited to sensory adaptation, might reflect broader brain regulatory properties that appear to be linked to personality traits.
The role of BDNF/PI3K/AKT/Nrf2 signaling in nicotine's protective effects against MPTP-induced Parkinson's disease.
Zhgenti N, Bakuradze E, Bibilashvili O … +1 more , Koshoridze N
Neurosci Lett · 2025 Nov · PMID 41077168 · Publisher ↗
Parkinson's disease (PD) is characterized by progressive loss of dopaminergic neurons in the substantia nigra, where oxidative stress and apoptosis play central roles. Epidemiological evidence suggests that nicotine may...
Parkinson's disease (PD) is characterized by progressive loss of dopaminergic neurons in the substantia nigra, where oxidative stress and apoptosis play central roles. Epidemiological evidence suggests that nicotine may exert neuroprotective effects, but the molecular mechanisms remain incompletely understood. This study investigated whether nicotine mitigates MPTP-induced neurotoxicity in mice through modulation of the BDNF/PI3K/AKT/Nrf2 signaling pathway. Male BALB/c mice were divided into control, nicotine, MPTP, and MPTP + nicotine groups. Histological analysis revealed that nicotine significantly reduced MPTP-induced neuronal pyknosis and preserved tyrosine hydroxylase-positive dopaminergic neurons. Biochemical assays showed that nicotine attenuated MPTP-induced increases in malondialdehyde, lactate dehydrogenase, and lactate/pyruvate ratio, while restoring complex I activity and antioxidant enzyme activities (SOD, CAT, GPx, GR). Western blotting demonstrated that nicotine reversed MPTP-induced suppression of phosphorylated PI3K, AKT, and Nrf2, and shifted apoptotic signaling toward survival by increasing Bcl-2 and reducing Bax and Bad. Importantly, nicotine restored BDNF levels in the substantia nigra, and ex vivo experiments confirmed that nicotine upregulated BDNF via α7 nicotinic acetylcholine receptor activation. These findings suggest that nicotine confers neuroprotection by enhancing BDNF-mediated activation of the PI3K/AKT/Nrf2 axis, leading to improved antioxidant defenses and anti-apoptotic signaling. In conclusion, nicotine mitigates MPTP-induced dopaminergic neurodegeneration via BDNF/PI3K/AKT/Nrf2 signaling. While nicotine's addictive properties limit its therapeutic use, selective targeting of nicotinic pathways may represent a promising strategy for disease-modifying interventions in PD.
Laughing your… brain off. New insights on the adaptive meaning of humour.
Vanutelli ME, Manfredi M
Neurosci Lett · 2025 Nov · PMID 41076236 · Publisher ↗
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Mitochondrial dysfunction and aging can be alleviated by modulating calcineurin and cardiolipin dynamics following stroke.
Bhattacharya P, Saraf S, Barik A … +3 more , Ghosh B, Datta A, Malik DS
Neurosci Lett · 2025 Nov · PMID 41062057 · Publisher ↗
The crucial influence of mitochondria in ischemic stroke pathophysiology presents many unexplored yet promising avenues for therapeutic strategies and clinical outcomes. Post-stroke mitochondrial dysfunction contributes...
The crucial influence of mitochondria in ischemic stroke pathophysiology presents many unexplored yet promising avenues for therapeutic strategies and clinical outcomes. Post-stroke mitochondrial dysfunction contributes to aggravated levels of calcium overload and apoptosis. This dysfunction is signified by disruption of the mitochondrial lipids such as cardiolipin, along with mitochondrial DNA mutation, leading to an imbalance in mitophagy. Calcium overload-mediated calcineurin overexpression has been reported to exacerbate mitochondrial damage and further contribute to neuronal apoptosis. In our study, we explored the alterations in the mitochondrial function following inhibition of the calcium-mediated calcineurin levels in post-stroke condition. In a rodent model of middle cerebral artery occlusion (MCAo), we observed that the inhibition of the calcium channels in post-stroke condition led to restored neuronal histology and viability following upregulation of the antioxidant levels. At the mitochondrial level, calcium channel inhibition downregulated calcineurin activation and normalized cardiolipin concentration, mitochondrial membrane potential, and respiratory control ratio in post-stroke condition. This inhibition also balanced the mitochondrial dynamics proteins and mitophagy towards neuronal recovery following ischemic stress. Moreover, it also normalized the expression of TERT, a key marker of mitochondrial health and aging. These findings highlight the role of calcium-mediated calcineurin in influencing mitochondrial dysfunction and aging in ischemic stroke. Thus, calcium channel inhibition offers a promising therapeutic strategy by preserving mitochondrial integrity and promoting neuroprotection following stroke.
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