Neurosci. Lett. [JOURNAL]
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200 papers
The effects of lithium chloride in N-methyl-N-nitrosourea induced retinal damage in rats.
İncili CA, Eröksüz Y, Eröksüz H … +1 more , Aslan A
Neurosci Lett · 2026 Feb · PMID 41390075 · Publisher ↗
The aim of the current study was to assess the potential neuroprotective effects of lithium chloride (LiCl) against retinal degeneration (RD) induced by N-methyl-N-nitrosourea (MNU) in the rats. 108 rats were assigned to...
The aim of the current study was to assess the potential neuroprotective effects of lithium chloride (LiCl) against retinal degeneration (RD) induced by N-methyl-N-nitrosourea (MNU) in the rats. 108 rats were assigned to 6 groups: Control, MNU (80 mg/kg), MNU + 30 mg/kg LiCI, MNU + 60 mg/kg LiCI, 30 mg/kg LiCI, and 60 mg/kg LiCI. The experimental groups comprised 18 rats each and the animals were euthanised on the 2nd, 7th and 14th days following the administration of MNU. Compared with the MNU group, both doses of LiCl significantly reduced retinal cell apoptosis and increased retinal thickness (P < 0.05). MNU group had a higher apoptotic index than the treatment groups, as evidenced by increased immunoreactivities of caspase-3, caspase-6, Bax, and 8-OHdG and decreased immunoreactivities of Bcl-2 at day 2. The outer nuclear layer (ONL) of the retina in rats treated with MNU exhibited a significant reduction in comparison the control group on both days 7 and 14 (P < 0.05). In contrast to the MNU-treated figgroup, the LiCl-injected rats exhibited a notable elevation in the expression levels of BDNF and Bcl-2 (P < 0.05). Conversely, the MNU-treated group exhibited markedly increased expression of GSK-3β, Bax, 8-OHdG, caspase-3, and caspase 6 (P < 0.05). In conclusion, LiCl demonstrated dose-dependent neuroprotective effects against MNU-induced RD in rats. These effects included a reduction in retinal cell apoptosis, an improvement in retinal thickness, and the potential involvement of anti-apoptotic mechanisms, glial activation inhibition, and neurotrophic factor modulation.
Bovine lactoferrin-induced antinociception through 5-HT receptors in formalin-induced tonic pain.
Ávila-Morales SE, Drago-Serrano ME, Godínez-Chaparro B
Neurosci Lett · 2026 Feb · PMID 41386373 · Publisher ↗
Bovine lactoferrin (bLF) is a multifunctional glycoprotein that displays modulatory effects on pain through pathways not fully known. Therefore, we determined the role of the serotonergic system as a potential mechanism...
Bovine lactoferrin (bLF) is a multifunctional glycoprotein that displays modulatory effects on pain through pathways not fully known. Therefore, we determined the role of the serotonergic system as a potential mechanism underlying the antinociceptive effect of bLF on formalin-induced tonic nociception. The formalin test was used to assess the antinociceptive effect-pain-like behaviour (flinching) at 1 h. The bLF-induced antinociceptive effect was prevented by the intrathecal (3 µg/rat), but not the intraplantar (30 µg/rat) administration of methiothepin, a non-selective 5-hydroxytryptamine (5-HT) antagonist. Moreover, intrathecal administration of WAY-100635 (6 µg/rat; selective 5-HT receptor antagonist) and BRL1555724 (4 µg/rat; selective 5-HT receptor antagonist) prevented the bLF-induced antinociceptive effect. However, intrathecal administration of SB-224289 (5 µg/rat; selective 5-TH receptor antagonist) and SB-699551 µg/rat; selective 5-TH receptor antagonist) did not prevent the bLF-induced antinociceptive effect. The above finding suggests that bLF reduces acute nociception induced by formalin, and this antinociceptive effect is mediated, at least in part, by the serotonergic system, acting only at the spinal level and not at the peripheral level, via activation of central 5-HT serotonergic receptors.
The anti-epileptic mechanism of a ketogenic diet regulating the gut microbiota via SIRT2 activation of the PI3K/AKT signaling pathway.
Li M, Deng H, Ma L … +1 more , Sun M
Neurosci Lett · 2026 Feb · PMID 41380905 · Publisher ↗
PURPOSE: Epilepsy (EP) is a disorder caused by sudden abnormal discharges of neurons in the brain. A ketogenic diet (KD) has significant anticonvulsant effects in some epileptic patients, but the signaling pathway remain...
PURPOSE: Epilepsy (EP) is a disorder caused by sudden abnormal discharges of neurons in the brain. A ketogenic diet (KD) has significant anticonvulsant effects in some epileptic patients, but the signaling pathway remains unclear. This study aims to investigate the mechanisms underlying the anticonvulsant effects of a KD. METHODS: Acute epilepsy models were induced by kainic acid (KA) and pentylenetetrazol (PTZ), synaptic electrical activity in the hippocampus was measured. The effects of KD on the expression levels of postsynaptic proteins and SIRT2 was determined, as well as the phosphorylation of the PI3K and Akt-S-473 signaling pathways. Metabolomic analysis was used to investigate the effect of KD on the gut microbiota. RESULTS: The KD inhibited acute seizures and promoted the amplitude of induced inhibitory postsynaptic current (IPSC) transmission and the frequency of spontaneous IPSC transmission in cortical brain regions. KD upregulated the expression of PI3K, activated the phosphorylation of AKT-S-473, and increased SIRT2 expression. Metabolomic analysis indicated shifts in host metabolism, particularly involving Clostridiales(e.g., Blautia and Lachnospiraceae). Based on existing literature, we hypothesize tha KD may support gut barrier function and anti-inflammatory responses. CONCLUSION: The anti-epileptic effect of KD in the prefrontal cortex is associated with the activation of the PI3K/Akt signaling pathway and an increase in SIRT2 expression. Additionally, our data are consistent with the emerging concept that the anti-seizure effects of KD may also involve modulation of the gut microbiota. This provides valuable insights for the development of new therapeutic interventions.
MEGF10 knockout promotes cortical and hippocampal amyloid deposition in AD mouse model.
Fujita Y, Yabe T, Yamada Y … +12 more , Kiuchi R, Nagase M, Nakamori R, Ichikawa S, Obara T, Yasuda H, Kurano J, Honda T, Komano H, Zou K, Tanabe Y, Maeda T
Neurosci Lett · 2026 Feb · PMID 41360178 · Publisher ↗
Multiple epidermal growth factor (EGF)-like domains 10 (MEGF10) is a single-pass transmembrane protein expressed in neurons and astrocytes, functioning as a phagocytic receptor for apoptotic cells and mediating homotypic...
Multiple epidermal growth factor (EGF)-like domains 10 (MEGF10) is a single-pass transmembrane protein expressed in neurons and astrocytes, functioning as a phagocytic receptor for apoptotic cells and mediating homotypic adhesion in the mammalian brain. We previously demonstrated that MEGF10 facilitates the uptake of toxic amyloid-β (Aβ) species Aβ42 and Aβ43 by neurons and astrocytes in vitro. However, whether MEGF10 also serves as a phagocytic receptor for Aβ in the brain in vivo, particularly under neurodegenerative conditions such as Alzheimer's disease (AD), remains unclear. To address this question, we generated MEGF10 knockout mice on an AD model background and analyzed brain Aβ deposition and Aβ42 levels. We observed a significant increase in Aβ deposition and Aβ42 levels in the hippocampus and cortex of MEGF10-deficient AD mice compared with AD model controls. To assess cognitive function, we performed the Y-maze test. MEGF10 knockout AD mice exhibited impaired spatial memory relative to wild-type controls; however, no significant difference was found between MEGF10 knockout AD mice and AD model controls. These findings suggest that MEGF10 contributes to Aβ clearance in the brain and support its role as a phagocytic receptor for Aβ in vivo, potentially helping to maintain brain homeostasis in the context of Alzheimer's pathology.
NNT inhibits microglial activation via mitochondrial oxidative stress in spinal cord injury.
Li M, Gu Q, Fan Z … +1 more , Duan C
Neurosci Lett · 2026 Feb · PMID 41354204 · Publisher ↗
Spinal cord injury (SCI) is a major public health challenge, often leading to severe neurological and physical disabilities. Microglia, the primary immune cells in the spinal cord, play critical roles in both the physiol...
Spinal cord injury (SCI) is a major public health challenge, often leading to severe neurological and physical disabilities. Microglia, the primary immune cells in the spinal cord, play critical roles in both the physiology and pathology of SCI. A deeper understanding of microglial activation is thus crucial for developing new therapeutic strategies. In this study, we observed that nicotinamide nucleotide transhydrogenase (NNT), a mitochondrial protein in eukaryotic cells, was upregulated in the injured spinal cord of mice, coinciding with elevated inflammatory factors and microglial activation. In vitro, lipopolysaccharide (LPS) induced microglial activation and increased NNT expression in BV2 cells. NNT overexpression effectively mitigated LPS-induced inflammation, proliferation, and oxidative stress in BV2 microglia. Furthermore, treatment with the mitochondria-targeting peptide SS-31 reduced mitochondrial superoxide levels. SS-31 also suppressed the inflammatory, proliferative, and oxidative stress responses caused by NNT deficiency in BV2 cells. Critically, in vivo overexpression of NNT in the spinal cord attenuated microglial activation and promoted functional recovery after SCI. Our findings reveal that NNT suppresses microglial activation by modulating mitochondrial oxidative stress, offering a promising therapeutic avenue for SCI.
The impact of guanethidine-induced sympathectomy on satellite glial cell activation in a rat model of neuropathic pain.
Han X, Jiang X, Liu Y … +1 more , Chen G
Neurosci Lett · 2026 Feb · PMID 41344494 · Publisher ↗
The involvement of satellite glial cells (SGCs) in neuropathic pain has been well-established; however, it remains unclear whether the sprouted sympathetic fibers within the dorsal root ganglion (DRG) after peripheral ne...
The involvement of satellite glial cells (SGCs) in neuropathic pain has been well-established; however, it remains unclear whether the sprouted sympathetic fibers within the dorsal root ganglion (DRG) after peripheral nerve injury affect the activation of SGCs. A rat model of neuropathic pain induced by spinal nerve ligation injury (SNL) was established. The mechanical withdrawal threshold (MWT) was evaluated using the von Frey test on postoperative days (POD) 1, 3, 7, and 14 to quantify mechanical allodynia. Immunofluorescence staining was performed to detect the expression of glial fibrillary acidic protein (GFAP, a marker for activated SGCs), tyrosine hydroxylase (TH, a marker for sympathetic nerve fibers), and α2-adrenergic receptor (α2-AR) in the ipsilateral DRG. Reversible sympathectomy was achieved by means of a single high-dose intraperitoneal injection of guanethidine (Gua). Western blotting(WB) was used to assess the effect of sympathectomy on GFAP expression in the DRG of SNL rats. After spinal nerve injury, the MWT of the ipsilateral hindlimb in rats decreased rapidly. Immunofluorescence results confirmed that the expression levels of GFAP and TH in the ipsilateral DRG of SNL rats gradually increased along with the development of mechanical allodynia. Notably, the co-expression of α2-AR and GFAP in the DRG gradually increased after SNL, suggesting that the newly formed noradrenergic-SGCs signaling within the DRG was involved in the initiation and maintenance of neuropathic pain. On 14 days post-SNL, Gua-induced sympathectomy significantly alleviated mechanical allodynia in rats and remarkably inhibited GFAP expression in the ipsilateral DRG. We concluded that in the rat model of neuropathic pain induced by SNL, the sprouted sympathetic fibers within the DRG may also participate in the maintenance of neuropathic pain by regulating the activation of SGCs.
Facilitation of supplementary motor area activity modulates the sense of effort: a theta burst stimulation study.
Okegawa T, Yamasaki D, Kaneko N … +1 more , Nakazawa K
Neurosci Lett · 2026 Feb · PMID 41338299 · Publisher ↗
The sense of effort, defined as the phenomenological experience of invested physical resources in the task, is a critical component of motor control. The supplementary motor area (SMA) has been implicated in generating t...
The sense of effort, defined as the phenomenological experience of invested physical resources in the task, is a critical component of motor control. The supplementary motor area (SMA) has been implicated in generating this sense, yet it remains unclear how modulating SMA activity affects unconscious motor output when individuals intend to exert the same level of effort. The present study aimed to investigate how inhibiting and facilitating SMA activity influences the subjective sense of effort and associated motor output. Twelve healthy volunteers received both facilitatory and inhibitory theta burst transcranial magnetic stimulation (TBS) applied to the SMA. We assessed corticospinal excitability, submaximal effort force production in an index finger abduction task (at a subjective effort level of 35% without visual feedback), and force-matching performance before and after the TBS protocols. Results showed that facilitatory TBS led to a significant reduction in the submaximal index finger abduction force, which was accompanied by decreased EMG activity. In contrast, inhibitory TBS did not produce significant changes in submaximal force. Importantly, TBS applied to the SMA did not significantly alter motor-evoked potentials, indicating that corticospinal excitability remained unchanged. These findings suggest that enhanced SMA activity increases the effort required to produce a given force. The underlying mechanism likely involves changes in efference copy signals, as the effect occurred without altering the corticospinal excitability. In addition, force-matching performance was improved at 30 min after facilitatory TBS applied to the SMA. This delayed behavioral improvement may suggest a time-dependent modulation of sensorimotor processing, possibly involving the SMA and posterior parietal cortex, although network-level mechanisms remain speculative. This study provides causal evidence for the SMA's role in processing effort-related signals and contributes to a growing understanding of the cortical mechanisms underlying the sense of effort.
Transcutaneous auricular vagus nerve stimulation promotes post-spinal cord injury remyelination via α7nAChR-mediated activation of oligodendrocyte precursor cells.
Min L, Cheng C, Chen J … +9 more , Ma C, Wang J, Tan M, Ran R, Wu X, Yan R, Hou J, Liu H, Feng Z
Neurosci Lett · 2026 Jan · PMID 41314506 · Publisher ↗
Transcutaneous auricular vagus nerve stimulation (ta-VNS) is a non-invasive neuromodulation technique with emerging therapeutic potential for various central nervous system diseases. However, its therapeutic effects and...
Transcutaneous auricular vagus nerve stimulation (ta-VNS) is a non-invasive neuromodulation technique with emerging therapeutic potential for various central nervous system diseases. However, its therapeutic effects and mechanisms in spinal cord injury (SCI) remain largely unexplored. In this study, we demonstrated that ta-VNS significantly improved motor function recovery in SCI patients. Diffusion tensor imaging (DTI) further indicated that ta-VNS promoted structural repair of injured axons and myelin sheaths. Using a rodent model of SCI, we found that ta-VNS facilitated remyelination, attenuated tissue damage, and enhanced motor function recovery. Mechanistically, ta-VNS upregulated the expression of the α7 nicotinic acetylcholine receptor (α7nAChR) in oligodendrocyte precursor cells (OPCs), promoting their proliferation and differentiation into mature oligodendrocytes, thereby supporting remyelination. These beneficial effects of ta-VNS were abolished by administration of a selective α7nAChR antagonist. This study identifies the α7nAChR-mediated pro-myelination axis as a novel mechanistic basis for ta-VNS therapy, thereby establishing this non-invasive neuromodulation as a compelling strategy for promoting repair and recovery after SCI.
Structure-function characterization of Olea dioica Roxb. PGK-1: Acetylcholinesterase inhibition, molecular docking, and amelioration of Aβ-induced toxicity in SH-SY5Y neuronal cells and the UAS-Aβ; ey-GAL4 drosophila model of Alzheimer's disease.
Pratap GK, G Nagaraju P, Joshi CG … +3 more , Sannegowda LK, Shantaram M, Priyadarshini P
Neurosci Lett · 2026 Feb · PMID 41314505 · Publisher ↗
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Involvement of substance P/NK1 receptor system in central sensitization in chronic pain.
Chen J, Lai Y, Li W
Neurosci Lett · 2026 Jan · PMID 41285348 · Publisher ↗
Chronic pain has become a serious health issue, affecting more than 30% of people worldwide. One of the main mechanisms of chronic pain is central sensitization. It is well known that substance P (SP) and its receptor, N...
Chronic pain has become a serious health issue, affecting more than 30% of people worldwide. One of the main mechanisms of chronic pain is central sensitization. It is well known that substance P (SP) and its receptor, Neurokinin 1 receptor (NK1R), play an important role in transmission of nociceptive signals. However, whether SP/NK1R system is involved in central sensitization in chronic pain remains controversial. In the present study, we adopted spared nerve injury (SNI) mouse model to induce neuropathic pain and assessed the role of SP/NK1R system in the development of hyperalgesia and central sensitization. We observed that hyperalgesia occurred in non-injured body part of SNI mice in tail withdrawal test. We also demonstrated hyperexcitability of S1 apical dendrites in SNI mice. Notably, the hyperalgesia behavior and hyperactivity of S1 apical dendrites were alleviated by NK1R antagonist L-703606. These results indicate that SP/NK1R system is involved in central sensitization in chronic pain.
TEMPOL alleviated tau pathology and cognitive deficits induced by P301S-tau.
Li X, Liu R, He Y … +3 more , Yang X, Li T, Feng Y
Neurosci Lett · 2026 Jan · PMID 41285347 · Publisher ↗
Alzheimer's disease (AD) is the most frequent of neurodegenerative disease affecting elderly people. However, there is still no curative therapeutic strategies in clinical practice. Here, we studied whether TEMPOL as a f...
Alzheimer's disease (AD) is the most frequent of neurodegenerative disease affecting elderly people. However, there is still no curative therapeutic strategies in clinical practice. Here, we studied whether TEMPOL as a free radical scavenger can prevent memory deficits in P301S-tau mice. We found that TEMPOL administration markedly restored learning and memory impairments inducing by P301S-tau. We showed that TEMPOL had a potent capacity of inhibiting the expression of tau protein and its phosphorylation levels. The inflammatory response and synaptic defects induced by P301S-tau was also obviously improved TEMPOL treatment. Furthermore, proteomics showed 121 reversed proteins by TEMPOL treatment were primarily involved in immune system processes, innate immune responses, inflammatory responses, autophagosome assembly, lysosome organization, and autophagy. Taken together, TEMPOL played a critical role in P301S-tau-related cognitive impairments. These findings demonstrate that TEMPOL shows promise as a multi-target therapeutic agent for AD by modulating critical pathways implicated in its pathogenesis.
Involvement of the right inferior parietal lobule network in ipsilateral spatial attention.
Iwakiri M, Takeo Y, Ikeda T … +2 more , Hara M, Sugata H
Neurosci Lett · 2026 Jan · PMID 41274597 · Publisher ↗
Unilateral spatial neglect (USN) significantly impairs mobility in patients following a stroke. The amount and quality of evidence supporting effective treatments for USN is still limited, primarily due to the unclear na...
Unilateral spatial neglect (USN) significantly impairs mobility in patients following a stroke. The amount and quality of evidence supporting effective treatments for USN is still limited, primarily due to the unclear nature of its underlying neural mechanisms. As lesions in USN are not localized to a specific brain region, research has underscored the importance of evaluating USN from a network-based perspective. Nevertheless, the key functional regions at the core of this network are yet to be identified. Previously, we reported that the right inferior parietal lobule (IPL) may serve as the central hub in the neural network associated with USN. Therefore, this study aimed to determine the brain network centered on the right IPL by conducting seed-based functional connectivity analysis. Our results may contribute to a better understanding of the neural mechanisms in USN.
Piracetam reverses scopolamine-induced memory disorder in mice: an animal model using behavioral, oxidative, and cholinesterase biomarkers.
da Silva Lima V, Emerick GL, Gindri Sinhorin VD … +8 more , da Silva Lima RR, da Silva HS, da Silva KF, Alves de Sousa AC, Silveira FR, Mizuno Saito AL, Estevam EL, Latorraca MQ
Neurosci Lett · 2026 Jan · PMID 41271014 · Publisher ↗
Memory impairment diseases have become a serious health problem worldwide. In this context, an animal model capable of recognizing substances with the ability to recover memory disorders would be welcome. Thus, the prese...
Memory impairment diseases have become a serious health problem worldwide. In this context, an animal model capable of recognizing substances with the ability to recover memory disorders would be welcome. Thus, the present work aims to evaluate the effect of piracetam on reversal of scopolamine-induced memory deficit in male Swiss mice (n = 6) after fifteen days of treatment. To achieve this objective, behavioral, oxidative and cholinesterase inhibition markers were used. Memory impairment was evaluated by object and social recognition and step-down inhibitory avoidance tests. The evaluation of the redox state included superoxide dismutase, catalase, glutathione-s-transferase, glutathione peroxidase, thiobarbituric acid reactive substances, carbonyl proteins, ascorbic acid, and reduced glutathione. Scopolamine caused cognitive deficit, evidenced by the reduction in latency period and in the discrimination index (DI) of aversive, social, and declarative memories. However, piracetam significantly reversed those deficits. Scopolamine has increased the levels of thiobarbituric acid reactive substances. Scopolamine inhibited significantly brain and plasma cholinesterase activity. In conclusion, scopolamine at a dose of 0.8 mg/kg for 15 days induced memory deficit, oxidative damage and cholinesterase inhibition in brain of mice. Furthermore, piracetam at a dose of 200 mg/kg could reverse the memory impairment induced by scopolamine by mechanisms that are independent of the antioxidant action and cholinesterase inhibition. The present model has showed great sensibility and could be used to evaluate other drugs with the potential for the treatment of diseases related to memory damage.
Alcohol-induced neuropathy associated downregulation of Kv7 channels in primary nociceptors.
Altinok FA, Dallali I, Hasan A … +3 more , Boubekka A, Tilki EK, Ozturk Y
Neurosci Lett · 2026 Jan · PMID 41265632 · Publisher ↗
Chronic alcohol consumption is a well-known risk factor for peripheral neuropathy, often presenting with thermal hyperalgesia and mechanical allodynia. While the involvement of dorsal root ganglia (DRG) neurons in alcoho...
Chronic alcohol consumption is a well-known risk factor for peripheral neuropathy, often presenting with thermal hyperalgesia and mechanical allodynia. While the involvement of dorsal root ganglia (DRG) neurons in alcohol-induced neuropathy (AIN) is recognized, the molecular mechanisms-particularly the role of Kv7-KCNQ potassium channel remains insufficiently understood. This research focused on evaluating the impact ofchronic alcohol exposure on Kv7 channel function and gene expression in DRG neurons, focusing on the KCNQ2 and KCNQ5 subunits.A rat model of AIN was established via oral gavage administration of 35 % ethanol (10 g/kg, twice daily) for 10 weeks. Pain hypersensitivity was evaluated using the electronic von Frey and Hargreaves tests. Quantitative real-time PCR was used to evaluate the mRNA expression of KCNQ2 and KCNQ5 channels. M-current (IM) density and neuronal excitability were assessed through whole-cell voltage-clamp and current-clamp recordings, respectively.Chronic ethanol exposure significantly reduced both mechanical and thermal thresholds, confirming the development of neuropathic pain. We observed a marked downregulation in the mRNA expression of KCNQ2 and KCNQ5 subunits, accompanied by a diminished M-current density within DRG neurons. These alterations were linked to increased neuronal excitability and heightened pain sensitivity in rats exposed to ethanol.These findings demonstrate that AIN is marked by a significant downregulation of KCNQ2 and KCNQ5 channel expression and function, contributing to elevated neuronal excitability and the onset of thermal hyperalgesia and mechanical allodynia. The suppressed activity of KCNQ/M channels within DRG neurons of AIN rats highlights Kv7 channels as promising molecular targets for AIN therapy.
Everolimus ameliorates cognitive deficits and synaptic dysfunction in mice with prefrontal cortical ADNP knockdown.
Xiang Y, Zhang Z, Jiang Y … +1 more , Wei H
Neurosci Lett · 2026 Jan · PMID 41265631 · Publisher ↗
Activity-dependent neuroprotective protein (ADNP), a major risk gene for autism spectrum disorder (ASD) and intellectual disability (ID), is critical for brain development and cognition. Among its regulated processes, au...
Activity-dependent neuroprotective protein (ADNP), a major risk gene for autism spectrum disorder (ASD) and intellectual disability (ID), is critical for brain development and cognition. Among its regulated processes, autophagy is notably affected, with mTORC1 overactivation acting as a negative regulator and frequently reported in ASD. Rapamycin can rescue ASD-related behaviors, and everolimus (EVR), an optimized derivative, is widely applied in clinical practice. However, its role in ADNP-related pathology remains unknown. Here, we established a prefrontal cortex (PFC) ADNP knockdown (KD) mouse model to examine behavioral and molecular consequences, and whether EVR provides benefit. We found that ADNP KD resulted in mTORC1 pathway activation, autophagy impairment, learning and memory deficits, and anxiety-like behaviors, concurrent with dysregulation of microtubule and synaptic proteins. Daily intraperitoneal EVR (5 mg/kg) can effectively alleviate the behavioral and molecular phenotypes caused by ADNP deficiency in the PFC, thereby establishing a strong rationale for targeting the mTOR pathway in treating ADNP-related cognitive impairments.
Constraint-induced movement therapy combined with Nogo-A downregulation enhances corticospinal tract remodeling and motor function in hemiplegic cerebral palsy mice.
Huang Y, Xie Y, Liu L … +9 more , Fan D, Le W, Zhang X, Peng T, Li W, Lin H, He L, Tang H, Xu K
Neurosci Lett · 2026 Jan · PMID 41248798 · Publisher ↗
Constraint-induced movement therapy (CIMT) enhances hand function in hemiplegic cerebral palsy (HCP) and stroke, partly by strengthening corticospinal tract (CST) projections, while down-regulated Nogo-A has been shown t...
Constraint-induced movement therapy (CIMT) enhances hand function in hemiplegic cerebral palsy (HCP) and stroke, partly by strengthening corticospinal tract (CST) projections, while down-regulated Nogo-A has been shown to facilitate neural regeneration in stroke and multiple sclerosis. However, their combined therapeutic effect remains unclear. Therefore, this study explored the impact of CIMT combined with Nogo-A downregulation on CST remodeling and motor function in HCP mice. Mice were randomly assigned to five groups: control, HCP, HCP + CIMT, HCP + SN (siRNA-Nogo-A treatment) and HCP + SN + CIMT. Rotarod and grip test were performed to assess the motor function. Western blot and immunofluorescence staining were performed to quantify Nogo-A and PKCγ expression in the M1 region. Diffusion tensor imaging and transmission electron microscopy were applied to assess fractional anisotropy (FA) of CST and myelin remodeling. Compared with controls, the HCP group exhibited significant motor dysfunction and myelin impairment, characterized by increased Nogo-A expression, decreased PKCγ expression, and reduced FA value of CST (p < 0.05). In contrast, mice treated with CIMT or SN exhibited improved motor function, reduced Nogo-A expression, elevated PKCγ expression, increased FA value of CST, and enhanced myelin remodeling compared with the HCP group (p < 0.05). Notably, CIMT and SN exerted synergistic effects, as the HCP + SN + CIMT group outperformed either single-treatment group (p < 0.05). These findings suggest CIMT combined with Nogo-A downregulation synergistically enhances motor function in HCP mice by reducing Nogo-A expression in M1 region and promoting CST remodeling.
Reducing surgical complexity in SAH models: A modified approach for reliable early and long-term brain injury replication.
Zhao X, Zhang S, Jiang S … +8 more , Yan Z, Liao J, Tian Q, Liu C, Han W, Wang G, Wang L, Li M
Neurosci Lett · 2026 Jan · PMID 41241307 · Publisher ↗
Among subarachnoid hemorrhage (SAH) models, the endovascular perforation method is widely used but limited by complex procedures and low efficiency. In this study, we developed a modified SAH model in male C57BL/6 mice b...
Among subarachnoid hemorrhage (SAH) models, the endovascular perforation method is widely used but limited by complex procedures and low efficiency. In this study, we developed a modified SAH model in male C57BL/6 mice by permanently ligating the unilateral common carotid artery (CCA) while maintaining external carotid artery (ECA) patency. Using laser speckle imaging, neurological scoring, brain water content analysis, TUNEL-NeuN co-staining, and behavioral tests, we compared this modified model to the classical approach. The modified model replicated key early and long-term brain injury features-cerebral edema, neuronal apoptosis, hemodynamic changes and cognition impairment-while significantly reducing surgical time and mortality rate. Total cerebral perfusion 24 h post-SAH was higher, with no differences in edema, apoptosis, or neurological scores versus the classic ECA model. This modified SAH model offers a practical, efficient tool for translational SAH research without compromising pathophysiological accuracy.
Environmental enrichment prevents depression-like behaviours induced by immune system activation in male mice.
Kanashiro A, Medeiros P, Medeiros AC … +4 more , Ferreira FR, de Campos AC, Barichello T, Coimbra NC
Neurosci Lett · 2026 Jan · PMID 41241306 · Publisher ↗
Depression is a debilitating psychiatric illness, and its etiology as well as resistance to current pharmacological treatments are increasingly associated with low-grade inflammation. Environmental enrichment (EE), a par...
Depression is a debilitating psychiatric illness, and its etiology as well as resistance to current pharmacological treatments are increasingly associated with low-grade inflammation. Environmental enrichment (EE), a paradigm that combines sensory and cognitive stimulation, social interaction, and voluntary physical activity, has been widely used to alleviate depression-like behaviours in rodent models, focusing on exposure to psychosocial stressors. However, the potential benefits of EE against depression-like behaviours triggered by immune activation remain unexplored. In this study, male C57BL/6 mice were housed under standard conditions or in EE. After six weeks, mice received an intraperitoneal injection of either physiological saline (vehicle) or lipopolysaccharide (LPS), a potent immunologic stimulus. Twenty-four hours later, anhedonia and behavioural despair were evaluated using the tail suspension test (i.e., frequency, latency, and time of immobility) and the splash test (i.e., latency, frequency, and time of grooming), respectively. LPS administration induced behavioural alterations consistent with depression-like behaviours characterised by increased immobility and decreased grooming. Remarkably, EE exposure prevented the development of LPS-induced depression-like behaviours in the tail suspension test and improved specific parameters in the splash test. Taken together, these findings highlight the therapeutic potential of EE as a non-pharmacological strategy for preventing or alleviating immune system activation-associated depression.
Artemisinin attenuates quinolinic acid-induced neurotoxicity by suppressing neuroinflammatory and apoptotic gene expression in rats.
Arthur R, Shanker U, Singh M … +2 more , Singh TG, Kumar P
Neurosci Lett · 2026 Jan · PMID 41241305 · Publisher ↗
Neurotoxicity, characterised by the structural and functional disruption of the nervous system, remains a major contributor to the pathophysiology of neurodegenerative disorders. It is mostly caused by oxidative stress,...
Neurotoxicity, characterised by the structural and functional disruption of the nervous system, remains a major contributor to the pathophysiology of neurodegenerative disorders. It is mostly caused by oxidative stress, excitotoxicity, mitochondrial dysfunction, and neuroinflammation, which results in gradual neuronal damage and death. Despite breakthroughs in understanding its underlying principles, effective therapeutic strategies to alleviate neurotoxic harm are still limited. Beyond its antimalarial action, artemisinin, a sesquiterpene lactone obtained from Artemisia annua, has recently attracted attention for its strong anti-inflammatory, antioxidant, and neuroprotective qualities. QA was bilaterally injected directly into the rat striatum to simulate neurotoxic conditions, followed by a 21-day artemisinin treatment. On days 0, 14, and 21, motor coordination was evaluated through behavioural assessments, including narrow beam walking, the open field test, and rotarod performance. Striatal homogenates were tested for oxidative stress parameters. qRT-PCR was used for molecular investigations. Hematoxylin and eosin staining was used to investigate histopathological changes in the striatum. Results indicated that artemisinin mitigated neurotoxicity in the experimental rats. It reduced oxidative stress and inflammatory and apoptotic markers in striatal homogenates. In conclusion, artemisinin efficiently reduced neurotoxic damage, indicating its promise as a potential neuroprotective alternative for neurodegenerative diseases.
Intermittent mild skin cooling stimulation inhibits pineal melatonin secretion in urethane-anesthetized rats.
Watanabe N, Moriya M, Hotta H
Neurosci Lett · 2026 Jan · PMID 41237849 · Publisher ↗
Skin thermal stimulation can induce reflexive autonomic nerve responses and thereby influence endocrine functions. Melatonin, secreted from the pineal gland primarily under sympathetic control, exerts various physiologic...
Skin thermal stimulation can induce reflexive autonomic nerve responses and thereby influence endocrine functions. Melatonin, secreted from the pineal gland primarily under sympathetic control, exerts various physiological functions including sleep-wake rhythm regulation. Although photostimulation is a well-known regulator of melatonin secretion, the effect of skin thermal stimulation remains unclear. In this study, we investigated whether intermittent mild cooling stimulation of the skin alters melatonin secretion from the pineal gland in urethane-anesthetized rats. Animals were artificially ventilated, and their rectal temperatures were maintained using a heating pad and a lamp. Using in vivo microdialysis, pineal perfusate was collected every 20 min for 100 min during the animal's light phase and the melatonin concentrations were measured via ELISA. Intermittent cooling stimulation was applied to the skin of the trunk using a Peltier-based contact thermode by alternating the temperature between 30 °C and 15 °C (15 °C/s) for 20 min. Without cooling stimulation, the melatonin concentration in the pineal perfusate remained stable for 100 min. Cooling stimulation did not affect the melatonin concentration during application but reduced it for 40 min after the stimulation was discontinued. This suppression was abolished in rats with bilateral cervical sympathetic nerve transection. Our findings suggest that intermittent mild skin cooling stimulation reflexively suppresses pineal melatonin secretion through cervical sympathetic nerves.
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