Neurosci. Lett. [JOURNAL]
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200 papers
Modulatory effects of GLT-1 enhancer, MC-100093, on neuroinflammatory factors in mesocorticolimbic brain regions of female P rats exposed chronically to ethanol.
Bhowmik KK, Alotaibi A, Abou-Gharbia M … +2 more , Childers W, Sari Y
Neurosci Lett · 2026 Mar · PMID 41617146 · Full text
Chronic ethanol intake increases extracellular glutamate concentrations in important reward-related brain regions, including the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc), ultimately resulting in oxidat...
Chronic ethanol intake increases extracellular glutamate concentrations in important reward-related brain regions, including the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc), ultimately resulting in oxidative stress and inflammation. Recent studies from our laboratory demonstrated that MC-100093, a synthetic beta-lactam lacking antibacterial properties and functioning as a GLT-1 modulator, decreased ethanol consumption. This study examined the impact of the GLT-1 modulator, MC-100093, on chronic ethanol consumption and neuroinflammation in specific subregions of the NAc (core and shell) and mPFC (Prelimbic, PL; and Infralimbic, IL) in female alcohol preferring rats in a dose-dependent manner. MC-100093 treatment decreased ethanol consumption at both doses (100 and 150 mg/kg, i.p.) following a five-week drinking paradigm. MC-100093 attenuated ethanol-induced increase of the pro-inflammatory cytokines HMGβ-1 and TNF-α expression across all investigated mesocorticolimbic brain regions. Moreover, MC-100093 treatment attenuated the ethanol-induced increase of RAGE expression in these brain regions at both doses. MC-100093 treatment decreased ethanol consumption, and this behavioral outcome correlated with a reduction in pro-inflammatory markers, indicating that MC-100093 may serve as a potential agent for mitigating the effects of chronic ethanol exposure associated with inflammation.
Effects of vestibular habituation training on synaptic plasticity in the medial prefrontal cortex of mice with motion sickness.
Fang S, Wang B, Zhang SL … +5 more , Wu H, Guo WW, Ren LL, Wang Y, Yang SM
Neurosci Lett · 2026 Mar · PMID 41611008 · Publisher ↗
BACKGROUND: Motion sickness (MS) is triggered by vestibular conflict, yet how vestibular habituation training (VHT) engages higher-order cortical circuits remains unclear. OBJECTIVE: To test whether VHT modulates medial...
BACKGROUND: Motion sickness (MS) is triggered by vestibular conflict, yet how vestibular habituation training (VHT) engages higher-order cortical circuits remains unclear. OBJECTIVE: To test whether VHT modulates medial prefrontal cortex (mPFC) activity and structural plasticity in a rotational MS model. METHODS: Male C57BL/6J mice were assigned to control (CON), motion sickness (MS), or vestibular habituation training (VHT) groups. MS was induced by a single 4-g session (four 1-min bouts; total 4 min), whereas VHT mice received 14 daily sessions (30 × 1-min bouts/day; total 30 min/day). Behavioral outcomes, core body temperature, c-Fos expression in the medial vestibular nucleus (MVN) and mPFC, and mPFC dendritic and spine morphology (Golgi-Cox) were assessed after the final exposure (MS: induction session; VHT: day-14 session). RESULTS: MS caused hypoactivity, impaired motor coordination, reduced sucrose preference, hypothermia, and increased c-Fos in the MVN and mPFC. After VHT, behavioral and autonomic measures returned to control-like levels. MVN c-Fos was reduced to a control-like range, whereas mPFC c-Fos was attenuated but remained above controls. Morphologically, MS increased dendritic length and complexity, reduced spine density, and did not alter spine width. VHT restored dendritic length and spine density, increased dendritic complexity further, and reduced spine width. CONCLUSION: VHT is associated with reduced MS-related neural activation and a distinct pattern of mPFC dendritic and spine remodeling, supporting higher-order cortical plasticity during vestibular habituation.
Characterization of calcium currents and their contributions to firing behaviour of primary motoneurons in developing zebrafish.
Gaudreau SF, Bui TV
Neurosci Lett · 2026 Mar · PMID 41565099 · Publisher ↗
Calcium currents in vertebrate motoneurons undergo developmental changes as motoneurons mature and develop specialized functions. The rapid development of zebrafish presents a unique opportunity to link changes in calciu...
Calcium currents in vertebrate motoneurons undergo developmental changes as motoneurons mature and develop specialized functions. The rapid development of zebrafish presents a unique opportunity to link changes in calcium currents of motoneurons to changes in the rapid and stereotyped motor maturation of zebrafish. As swimming matures from crude, large amplitude body bends to refined, low amplitude tailbeats, the involvement of the primary motoneurons that innervate fast muscle becomes less prevalent. During this time, primary motoneuron innervation, dendritic arborization, and firing properties become refined. In this study, we aimed to characterize the presence and influence on firing behaviour of low-voltage and high-voltage activated calcium currents in primary motoneurons during early development, when primary motoneurons undergo functional maturation. Our whole-cell patch-clamp electrophysiology data in zebrafish aged 2 to 5 days post-fertilization (dpf) reveal unique characteristics of calcium currents in zebrafish primary motoneurons, such as the influence of L-type and N-type calcium currents on the regulation of repetitive firing at 3 and 5 dpf, the emergence of P/Q-type calcium currents that regulate repetitive firing as of 4 dpf, and the absence of post-inhibitory rebounds characteristic of T-type calcium currents. These findings highlight how precise changes in properties of ion currents can shape neuronal function during development.
The distribution map of α4 and α7 subunits of nAch receptors in the olfactory bulb of male rat neonates born to STZ-induced hyperglycemia model mothers.
Baradaran R, Alipour N, Anbarkeh FR … +1 more , Ghandy N
Neurosci Lett · 2026 Mar · PMID 41558592 · Publisher ↗
BACKGROUND: Alpha4 and alpha7 nicotinic acetylcholine receptors (nAChRs) are critical for neuronal survival and are highly expressed in the rat olfactory bulb (OB). Gestational diabetes mellitus (GDM) affects the central...
BACKGROUND: Alpha4 and alpha7 nicotinic acetylcholine receptors (nAChRs) are critical for neuronal survival and are highly expressed in the rat olfactory bulb (OB). Gestational diabetes mellitus (GDM) affects the central nervous system, including the OB. This study investigates the effects of maternal diabetes on the distribution of alpha4 and alpha7 nAChR subunits in the OB of male rat neonates. METHODS: Timed-pregnant female Wistar rats were randomly assigned to three groups: Control (no intervention), Stz (streptozotocin, 45 mg/kg, i.p.), and Stz + Ins (streptozotocin, 45 mg/kg, i.p., plus 4-6 units of Neutral Protamine Hagedorn insulin, subcutaneous daily). One week after STZ-induced hyperglycemia confirmation, females were mated with non-diabetic males, with vaginal plaque observation marking gestation day 1. After natural childbirth, Male pups were divided into two age subgroups: postnatal day 7 (P7, n = 4) and postnatal day 14 (P14, n = 4). Brains were extracted for immunohistochemical analysis of alpha4 and alpha7 nAChR expression and dark neuron counts. RESULTS: The optical density (OD) of alpha4 and alpha7 nAChRs in the Stz group was significantly lower than in the Control group across all OB layers at P7 and P14. Conversely, the Stz + Ins group exhibited significantly higher OD compared to the Stz group. Dark neuron counts were significantly elevated in the Stz group compared to the Control and Stz + Ins groups, particularly in the mitral cell layer. CONCLUSION: Maternal hyperglycemia reduces nAChR expression and increases dark neuron populations in the OB of neonatal rats, potentially contributing to olfactory dysfunction. Insulin treatment mitigates these adverse effects.
L17E cell-penetrating peptide enhances intranasal delivery of IgG to the cerebrospinal fluid in mice.
Hashikawa N, Terado T, Noda T … +5 more , Kashimoto R, Iima T, Oro M, Tambara S, Hashikawa-Hobara N
Neurosci Lett · 2026 Mar · PMID 41554326 · Publisher ↗
Antibody-based therapeutics are promising for treating central nervous system (CNS) diseases; however, brain delivery is severely restricted by the blood-brain barrier (BBB). Intranasal administration has gained attentio...
Antibody-based therapeutics are promising for treating central nervous system (CNS) diseases; however, brain delivery is severely restricted by the blood-brain barrier (BBB). Intranasal administration has gained attention as a noninvasive route proposed to reduce the impact of the BBB; however, the efficiency of delivering large biomolecules, such as antibodies, remains insufficiently characterized. This study aimed to investigate whether cell-penetrating peptides (CPPs) could increase detectable IgG levels in the cerebrospinal fluid (CSF) following intranasal administration in mice. Rabbit IgG was intranasally administered to ICR mice, either alone or in combination with CPPs (R9, Penetratin, or L17E). IgG levels in the CSF and serum were quantified by ELISA, and both time-course and dose-dependent effects were analyzed. IgG alone was not detected in the CSF, whereas serum IgG levels increased dose-dependently. Co-administration of Penetratin or L17E resulted in detectable CSF IgG levels, with L17E exceeding Penetratin. By contrast, no delivery was observed in the R9 group. Serum IgG levels also increased in the Penetratin and L17E groups. Time-course analysis with L17E showed that CSF IgG reached its highest measured level at 24 h and declined thereafter, whereas serum IgG reached higher levels at earlier time points and remained relatively stable. Dose-response analysis revealed linear increases in serum IgG, while CSF IgG levels depended on the concentration of L17E. These findings indicate that co-administration with amphipathic CPPs, particularly L17E, enables detectable IgG delivery to the CSF following intranasal administration in mice, although the underlying mechanisms and therapeutic relevance remain to be clarified.
Repeated exposure to motor imagery enhances focal brain activation during motor imagery practice after stroke.
Klick SM, Rubino C, Magnuson JR … +9 more , Penko L, Rajendran A, Denyer R, Jones CB, Brocato J, Lamb C, Schaurich C, Boyd LA, Kraeutner SN
Neurosci Lett · 2026 Mar · PMID 41548864 · Publisher ↗
Stroke results in motor impairments of the upper limbs, linked to altered activation in sensorimotor regions. Motor imagery (MI; the mental rehearsal of movement) activates sensorimotor regions, providing the basis for i...
Stroke results in motor impairments of the upper limbs, linked to altered activation in sensorimotor regions. Motor imagery (MI; the mental rehearsal of movement) activates sensorimotor regions, providing the basis for its effectiveness as an intervention for motor recovery after stroke. Yet, the effect of repeated MI on brain activation after stroke is unexplored. In this study, thirty-three individuals with stroke (>3 months) performed MI of an upper-limb movement using their paretic arm and hand across two sessions on two different days. Brain activation was obtained via functional magnetic resonance imaging (fMRI). Group-level contrasts revealed: 1) focal brain activation in Session 2 relative to Session 1, and 2) functional localization to sensorimotor regions. Together, these findings demonstrate that MI induces changes in brain activation after only two sessions in individuals with stroke, specifically encompassing activation in sensorimotor areas. Familiarizing individuals to MI prior to its use may improve applications of MI for learning and recovery.
Dose-dependent impact of extremely low-frequency electromagnetic field (ELF-EMF) on the neuroplasticity in the hippocampus of adult rats.
Klimiuk M, Kletkiewicz H, Wyszkowska J … +2 more , Dokladny K, Rogalska J
Neurosci Lett · 2026 Mar · PMID 41544927 · Publisher ↗
Extremely low-frequency electromagnetic field (ELF-EMF) therapy is gaining attention for its potential benefits in treating neurodegenerative conditions. However, the underlying molecular mechanisms responsible for the p...
Extremely low-frequency electromagnetic field (ELF-EMF) therapy is gaining attention for its potential benefits in treating neurodegenerative conditions. However, the underlying molecular mechanisms responsible for the possible protective effects of ELF-EMF remain unclear. Our previous research revealed that ELF-EMF exposure can establish a new "set-point" for stress responses, with outcomes dependent on field intensity. Stress hormones have been shown to modulate hippocampal function and plasticity. Therefore, our study aimed to assess how ELF-EMF exposure affects the expression of transcripts related to hippocampal plasticity, including genes related to neurogenesis (BDNF, TrkB, GAP43), synaptic activity (PSD95, SYN1), and cell survival (Bcl-2, Bcl-xL, Bak1). Adult rats were exposed to ELF-EMF (50 Hz) at 1 mT and 7 mT intensities for three 7-day periods, 1 h/day, with 3-week break between each cycle. A subset of animals was sacrificed after each exposure to collect hippocampi. The relative expression of neural/synaptic genes and anti-/pro-survival factors was measured by real-time quantitative polymerase chain reaction. Our findings indicate that ELF-EMF exposure modulates mRNA expression of neural/synaptic genes and anti-/pro-survival factors. The direction and dynamics of changes depend on ELF-EMF intensity and the number of exposures. "Low-intensity" ELF-EMF (1 mT) increased pro-neuroplastic factors expression, while "high-intensity" ELF-EMF (7 mT) decreased them. In summary, "low-intensity" ELF-EMF enhances adaptive processes like neuroplasticity by eliciting a mild stress response, while "high-intensity" exposure disrupts homeostasis and brain function by inducing severe stress. Our findings indicate that the overall effects of ELF-EMF depend on the intricate interplay between stress reactions and long-term brain plasticity.
Mutant glial fibrillary acidic protein reduces the capacity for glutamate uptake in hippocampal astrocytes.
Yamazaki Y, Fujiwara H, Goto JI … +1 more , Tanaka KF
Neurosci Lett · 2026 Mar · PMID 41539412 · Publisher ↗
Astrocytes preserve synaptic function and maintain excitatory-inhibitory balance by regulating neurotransmitter homeostasis, notably through the clearance of glutamate from the extracellular space. This process is essent...
Astrocytes preserve synaptic function and maintain excitatory-inhibitory balance by regulating neurotransmitter homeostasis, notably through the clearance of glutamate from the extracellular space. This process is essential for preventing excitotoxicity in the central nervous system. Mutations in glial fibrillary acidic protein (GFAP) are associated with astrocytic dysfunction, leading to neurological symptoms, e.g., seizures. Although such mutations are implicated in neurological disorders including Alexander disease, their direct impact on the astrocytic uptake of synaptically released glutamate has not been demonstrated. Here, we assessed glutamate uptake in hippocampal astrocytes of mice expressing mutant GFAP using whole-cell recordings of transporter-mediated currents in acute hippocampal slices. Glutamate release into the synaptic cleft varied according to the intensity of afferent fiber stimulation, but transporter current amplitudes did not differ significantly between mutant and control mice under baseline conditions. In contrast, when adenosine A receptors were blocked to relieve the tonic inhibition of glutamate release, transporter currents were significantly smaller in mutant mice than in controls at high stimulation intensities. These findings indicate that astrocytes expressing mutant GFAP exhibit impaired glutamate uptake capacity, which may be insufficient to prevent excitotoxicity or seizures under conditions of excessive glutamate release.
Medial prefrontal Cortex, dopamine and glutamate modulation in regulating Reward-Seeking and frustration responses.
de Oliveira Lima CA, da Silva Mendonça P, Crispim JG … +8 more , da Silva RL, Silva RC, de Melo Alcantara LF, Duarte FS, de Melo Rego MJ, da Rocha Pitta MG, Pereira MC, da Rosa MM
Neurosci Lett · 2026 Mar · PMID 41520996 · Publisher ↗
BACKGROUND: Behavior is often reinforced by rewarding experiences, which promote actions that yield positive outcomes contributing to adaptive decision-making. However, the absence of an anticipated reward can provoke ne...
BACKGROUND: Behavior is often reinforced by rewarding experiences, which promote actions that yield positive outcomes contributing to adaptive decision-making. However, the absence of an anticipated reward can provoke negative emotional responses, such as frustration and anxiety, potentially leading to maladaptive behaviors. Understanding how the brain responds to reward and its omission is a growing focus in neuroscience, especially regarding how neurotransmitter systems in key circuits manage unmet expectations. The medial prefrontal cortex (mPFC), a central integrative hub, regulates downstream regions to process both rewarding and aversive outcomes. Although dopamine is known to guide reward prediction and adaptive behavior, the specific roles of dopaminergic and glutamatergic pathways in the mPFC remain unclear. METHODS: In this study, we investigated the influence of mPFC and the differential roles of dopaminergic D2 and NMDA receptors within the mPFC on reward-seeking behaviors using a cued sucrose-seeking task. RESULTS: Our results show that D2 dopamine receptor and NMDA receptor activity in the mPFC are essential for maintaining reward-seeking behaviors when expected rewards are omitted, highlighting dopamine and glutamate's role in sustaining reward-persistent behavior. Conversely, only D2 blockade into mPFC affected cue-reward seeking behavior. Solely NMDA blockage in the mPFC and mPFC silencing reduced anxiety, suggesting a nuanced role for mPFC and glutamatergic signaling in managing the emotional response to unmet expectations. CONCLUSION: These findings provide new insights into how distinct neurotransmitter systems in the mPFC and mPFC itself contribute to the behavioral and emotional adjustments following reward and reward omission.
G protein-coupled receptor 17 promotes neuropathic pain in male mice by upregulating spinal NMDAR subunit expression.
Li B, Xu X, Xiao Q … +11 more , Zhang K, Yu X, Xiao Y, Lu S, Jin W, Sun P, Li L, Ma C, Lu Z, Wu Y, Ke C
Neurosci Lett · 2026 Feb · PMID 41519370 · Publisher ↗
Neuropathic pain is a prevalent and debilitating chronic condition for which current treatments often provide inadequate relief. This constitutes a significant unmet clinical need, highlighting the importance of identify...
Neuropathic pain is a prevalent and debilitating chronic condition for which current treatments often provide inadequate relief. This constitutes a significant unmet clinical need, highlighting the importance of identifying novel molecular targets for more effective pharmacotherapy. Synaptic remodeling-mediated central sensitization is a key regulatory factor. Glutamate is a major excitatory transmitter in the central nervous system and binds to NMDA receptors in the postsynaptic membrane to promote synaptic remodeling. In C57 mice with spared nerve injury, it was noted that GPR17 and the GluN2A and GluN2B subunits of the NMDA receptor were elevated in the L4-L6 region of the spinal cord. Lentiviral knockdown of spinal GPR17 attenuated mechanical allodynia, suppressed astrocyte activation, and decreased levels of GluN2A and GluN2B subunits. GPR17 controls neuropathic pain, stimulates astrocyte activation, and NMDA receptor overexpression on neurons. Targeting GPR17 may represent a new therapeutic strategy for the management of neuropathic pain.
Differential neuroinflammatory trajectories in the hippocampus and prefrontal cortex after acute LPS administration.
Yue Z, Li M, Wang J … +4 more , Quan S, Wang Y, Niu Z, Li Y
Neurosci Lett · 2026 Mar · PMID 41519369 · Publisher ↗
Neuroinflammation is a key pathological feature of central nervous system disorders, yet its temporal and regional dynamics remain poorly defined. In this study, we systematically investigated neuroinflammatory responses...
Neuroinflammation is a key pathological feature of central nervous system disorders, yet its temporal and regional dynamics remain poorly defined. In this study, we systematically investigated neuroinflammatory responses and neuronal injury in the hippocampus and prefrontal cortex following a single intraperitoneal injection of lipopolysaccharide (LPS, 1 mg/kg) in mice. Fifty-four male C57BL/6N mice were randomly divided into six groups, and serum and brain tissues were collected at 0, 3, 6, 12, 24, and 48 h after LPS administration. Cytokine levels were detected by enzyme-linked immunosorbent assay (ELISA), neuronal injury was assessed by Nissl staining, and proteins expression was examined by Western blot. The results showed that peripheral cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), exhibited a rapid and transient increase, peaking at 3 h and returning to baseline within 24 h, whereas central inflammatory responses displayed marked region- and time-dependent differences. In the hippocampus, IL-1β showed delayed but sustained elevation, peaking at 12 h and accompanied by progressive neuronal injury. In contrast, the prefrontal cortex exhibited an early cytokines surge at 3 h, with prolonged IL-1β elevation, and a biphasic pattern of neuronal damage characterized by early injury, partial recovery, and delayed exacerbation. These spatiotemporal dynamics were paralleled by differential activation of the TLR4/MyD88/NF-κB pathway. These findings reveal that LPS-induced neuroinflammation is a heterogeneous and dynamic process rather than a uniform response, providing new insight into region-specific vulnerability and the dissociation between peripheral and central inflammatory kinetics.
Enhanced antidepressant effects of fluoxetine combined with quercetin: studies in vitro and in vivo.
Yang R, Mao Y, Yang J … +2 more , Ma H, Shen J
Neurosci Lett · 2026 Mar · PMID 41519368 · Publisher ↗
OBJECTIVES: This study aims to explore the enhanced antidepressant effects of the commonly used depressant fluoxetine combined with a dietary supplement quercetin, using both in vitro and in vivo models. METHODS: In vitr...
OBJECTIVES: This study aims to explore the enhanced antidepressant effects of the commonly used depressant fluoxetine combined with a dietary supplement quercetin, using both in vitro and in vivo models. METHODS: In vitro, we established both hydrogen peroxide (HO)-damaged and glutamate-damaged SH-SY5Y cells as cellular models. SH-SY5Y cells were exposed to 250 μM HO or 16 mM glutamate and co-treated with 1 μM fluoxetine, 10 μM quercetin, or their combination for 24 h. Cell viability was detected.In vivo, we applied a chronic unpredictable mild stress (CUMS) animal model. C57BL/6 mice were treated with fluoxetine (5 or 10 mg/kg), quercetin (40 mg/kg), or their combinations. Depressive-like behaviors including Sucrose preference test (SPT), Tail suspension test (TST), and Forced swimming test (FST) were assessed. Nissl staining was carried out for observing changes in hippocampal neurons. RESULTS: Fluoxetine combined with quercetin protected SH-SY5Y cells from HO- or glutamate-induced damage, improved depressive-like behaviors and reduced hippocampal neuronal injury in CUMS mice, demonstrating enhanced antidepressant effects compared to monotherapy. CONCLUSION: Combining fluoxetine with quercetin enhances antidepressant effects, suggesting a way to reduce the clinically required dosage of fluoxetine, thereby reducing its side effects.
Comparative effects of antidepressants on cocaine-induced hyperthermia in rats: a preclinical study.
Okada T, Obi S, Takano M … +2 more , Shioda K, Suda S
Neurosci Lett · 2026 Feb · PMID 41512926 · Publisher ↗
PURPOSE: Cocaine abuse is a major public health concern and is often associated with acute hyperthermia, which can be fatal and has limited pharmacological interventions for its management. Although antidepressants are f...
PURPOSE: Cocaine abuse is a major public health concern and is often associated with acute hyperthermia, which can be fatal and has limited pharmacological interventions for its management. Although antidepressants are frequently prescribed to cocaine users, particularly to those with comorbid depression, their safety within this context remains unclear, as some can exacerbate the toxicity of cocaine. This study aimed to evaluate the effects of various antidepressants on cocaine-induced hyperthermia in rats to identify safer treatment options. SUBJECTS AND METHODS: Adult male Wistar rats received intraperitoneal injections of cocaine (30 mg/kg) following pretreatment with one of the following antidepressants: mirtazapine, fluoxetine, venlafaxine, amitriptyline, or moclobemide. To elucidate the mechanism underlying the effects of mirtazapine, the selective 5-HT2A receptor antagonists ketanserin and ritanserin were also tested. Rectal temperature was measured every 30 min for up to 240 min after cocaine administration. RESULTS: Cocaine administration significantly elevated body temperature in control rats. However, pretreatment with mirtazapine significantly suppressed this hyperthermic response, presumably via central 5-HT2A receptor antagonism. Ketanserin and ritanserin similarly suppressed hyperthermia, supporting this proposed mechanism. In contrast, moclobemide exacerbated the hyperthermia, venlafaxine prolonged the hyperthermic response, and fluoxetine and amitriptyline had no significant effect on the hyperthermic response. CONCLUSION: Mirtazapine may be a safer antidepressant option for managing depression in cocaine users because of its capacity to suppress hyperthermia without enhancing monoamine reuptake inhibition. Notably, caution should be exercised when prescribing monoamine oxidase inhibitors and SNRIs to this population. However, further clinical studies are required to validate these findings.
Electroacupuncture at GV20 and GV24 acupoints ameliorates migraine by blocking NLRP3-mediated pyroptosis via inhibiting the Piezo1 channel.
Luo J, Feng L, Xu W … +4 more , Lang J, Wang L, Zhao Z, Lang B
Neurosci Lett · 2026 Mar · PMID 41506593 · Publisher ↗
Migraine is a complex neuro-glio-vascular disorder, and electroacupuncture (EA) have been recommended as an alternative therapy for migraine. However, the mechanism of action of EA on GV20 (Baihui) and GV24 (Shenting) ac...
Migraine is a complex neuro-glio-vascular disorder, and electroacupuncture (EA) have been recommended as an alternative therapy for migraine. However, the mechanism of action of EA on GV20 (Baihui) and GV24 (Shenting) acupoints in treating migraine remains unclear. Thus, this study was performed to explore the potential mechanisms underlying the therapeutic influence of EA stimulation at GV20 and GV24 acupoints in the migraine treatment. After therapeutic effects of EA stimulation at GV20 and GV24 acupoints on migraine rat model established by dural electrical stimuli (DES) stimulation exploration, numerous approaches, such as qRT-PCR, immunofluorescence, and western blot, were applied to assess the expression of Piezo1 and pyroptosis-related proteins. Finally, Piezo1 activator (Yoda1) was used to confirm the involvement of Piezo1 channel in the treatment actions of EA stimulation at GV20 and GV24 acupoints on migraine. The results showed that EA stimulation at GV20 and GV24 acupoints forcefully alleviated the mechanical allodynia and central sensitization in rat model of migraine, also downregulated the expression of pro-inflammatory cytokines, containing TNF-α, IL-6, and IL-1β. In addition, EA stimulation at GV20 and GV24 acupoints also changed the expression of Piezo1 and pyroptosis-related proteins in rat model of migraine. Interestingly, treatment with the Yoda1 could reverse the therapeutic influences of EA stimulation at GV20 and GV24 acupoints in migraine rat model. Of note, the effect of EA stimulation at GV20 and GV24 acupoints on the expression of pyroptosis-related proteins could also be reverse by Yoda1 administration. This study emphasizes the EA efficacy at GV20 and GV24 acupoints on the migraine rat model established by DES stimulation, and proposes a mechanism involving inhibition of Piezo1 channel to block NLRP3-mediated pyroptosis in migraine.
The role of childhood trauma in hippocampal subfield alterations in lithium-treated type I bipolar disorder and healthy controls: A subfield volumetry MRI study.
Aparecido-de-Almeida J, Soeiro-de-Souza MG
Neurosci Lett · 2026 Mar · PMID 41494570 · Publisher ↗
BACKGROUND: Type I bipolar disorder (BD-I) affects approximately 1% of the global population, and alterations in the morphology of the hippocampus, a cerebral region critical for memory and emotional regulation, may play...
BACKGROUND: Type I bipolar disorder (BD-I) affects approximately 1% of the global population, and alterations in the morphology of the hippocampus, a cerebral region critical for memory and emotional regulation, may play an important role in its pathophysiology. Childhood Adversity (CA), including abuse and neglect, has been linked to structural hippocampal changes and elevated psychiatric risk, yet the impact of CA on hippocampal subfields in BD remains poorly understood. METHODS: Eighty‑five euthymic patients with BD-I on stable lithium therapy (age 18-40), and 59 healthy controls were assessed (both groups trauma-exposed with score of Childhood Trauma Questionnaire (CTQ) > 25). Volumes of 12 hippocampal subfields were measured using FreeSurfer v6.0.0 and ENIGMA protocols. Partial correlations between CTQ subscale scores and subfield volumes were identified, controlling for age, sex, lithium use, and intracranial volume. RESULTS: In the BD-I group, higher physical neglect scores correlated with larger right hippocampal volumes: total hippocampus, CA1, hippocampal fissure, and presubiculum, whereas high emotional abuse scores were associated with increased left hippocampal fissure and subiculum volume. No significant associations were observed in controls, indicating specificity of trauma‑related alterations in BD-I. CONCLUSION: Different CA subtypes yield distinct volumetric signatures in BD-I: physical neglect seems to drive expansion especially in right‑hemisphere subfields, while emotional abuse appears to enlarge the left subiculum. These findings highlight potential neuroplasticity biomarkers and may help inform early and targeted interventions.
Prolonged exposure of cerebrocortical neurons to diazepam induces downregulation of surface α1-containing GABA receptors and uncoupling of GABA/benzodiazepine site interactions through different mechanisms.
González Gómez LC, Gravielle MC
Neurosci Lett · 2026 Feb · PMID 41448450 · Publisher ↗
GABA receptors play a crucial role in mediating fast inhibitory neurotransmission in the central nervous system. These receptors are targets of numerous pharmacological agents used clinically to control neuronal excitabi...
GABA receptors play a crucial role in mediating fast inhibitory neurotransmission in the central nervous system. These receptors are targets of numerous pharmacological agents used clinically to control neuronal excitability in different neurological disorders. Sustained stimulation of GABA receptors by endogenous or exogenous modulators leads to adaptive homeostatic alterations in the receptor function. In particular, chronic benzodiazepine administration results in tolerance to most of the behavioral effects, limiting the clinical use of these drugs for long-term treatments. In previous studies, we found that prolonged exposure of rat cerebrocortical neurons to diazepam produces uncoupling of GABA/benzodiazepine site interactions and decreased expression of the GABA receptor α1 subunit gene, mediated by a mechanism involving the activation of L-type voltage-gated calcium channels (L-VGCCs). This work aimed to further explore the molecular basis of GABA receptor regulation induced by prolonged benzodiazepine stimulation. Our findings indicate that diazepam increases intracellular calcium levels, confirming the dependence of benzodiazepine-induced GABA receptor regulation on calcium entry through L-VGCCs. Immunocytochemical analyses revealed that sustained diazepam treatment reduces the expression of α1-containing GABA receptors on the cell surface, which likely impacts functional receptors. By knocking-down α1 subunit expression, we demonstrated that α1 downregulation alone results in minor, non-significant uncoupling, suggesting that additional GABA receptor modifications contribute to the observed uncoupling. Altogether, our results suggest that persistent exposure of GABA receptors to benzodiazepines produces uncoupling and downregulation of functional α1-containing GABA receptors through two distinct mechanisms, both initiated by calcium influx through L-VGCCs.
Recovery from cuprizone induced incontinence is not dependent upon remyelination.
Lahiri A, Papile LE, Dhari Z … +5 more , Lustig JT, Lombardo ET, Lavoie ER, Sutter PA, Crocker SJ
Neurosci Lett · 2026 Feb · PMID 41435926 · Publisher ↗
Dysfunction in bladder control (incontinence) is a significant comorbidity in multiple sclerosis that diminishes patients' quality of life and is a leading cause of hospitalization. Recent evidence indicates that CNS dem...
Dysfunction in bladder control (incontinence) is a significant comorbidity in multiple sclerosis that diminishes patients' quality of life and is a leading cause of hospitalization. Recent evidence indicates that CNS demyelination is sufficient to induce incontinence, while bladder control is also restored following remyelination. Based on this strong association, we hypothesized that remyelination is necessary for the restoration of bladder function control after acute demyelination. To test this, we evaluated changes in bladder function in mice in which Myelin regulatory factor (Myrf) was conditionally knocked out in oligodendrocyte precursor cells (OPC)(PDGFR⍺- CreER, Myrf (Myrf-cKO)) and compared these with control groups during and after being subjected to cuprizone treatment. Here, we report that acute demyelination leads to bladder control dysfunction which was evidenced by significantly increased voiding behavior irrespective of genotype. However, during the remyelination phase, we observed an amelioration of incontinence in all groups, including mice in which remyelination fails (e.g. Myrf-cKO mice). These data suggest that while active demyelination can initiate loss of bladder function control, failed remyelination is not an impediment to potential adaptive changes which may facilitate restoration of proper bladder function.
Chlorogenic acid exerts anti-inflammation and neuroprotective effect in pentylenetetrazole-induced epilepsy mouse model by regulating microglia polarization via Nrf2/HO-1 pathway.
Sun Y, Wang J, Zhang A … +2 more , Hu A, Wu L
Neurosci Lett · 2026 Feb · PMID 41423014 · Publisher ↗
Chlorogenic acid (CGA) possesses diverse biological functions, including antioxidant, anti-inflammatory, and anti-apoptotic, both in vitro and in vivo. Recent studies have suggested that CGA also has neuroprotective effe...
Chlorogenic acid (CGA) possesses diverse biological functions, including antioxidant, anti-inflammatory, and anti-apoptotic, both in vitro and in vivo. Recent studies have suggested that CGA also has neuroprotective effects. However, its potential to alleviate seizures and attenuate epilepsy-related neuropathology remains unclear. This study investigated the effects and underlying mechanisms of CGA in a pentylenetetrazole (PTZ)-induced epilepsy mouse model. CGA treatment significantly reduced epileptic seizures. Nissl and NeuN immunofluorescence staining revealed that CGA also significantly reduced neuronal damage. Furthermore, CGA promoted microglial polarization from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype and suppressed neuroinflammation, evidenced by iNOS/IBA-1 and Arg-1/IBA-1 immunofluorescence and RT-PCR. BrdU staining revealed that CGA inhibited epilepsy-induced aberrant neurogenesis. In addition, behavioral tests showed improved cognitive performance following CGA treatment. Finally, western blot analysis indicated the activation of the Nrf2/HO-1 pathway, and Nrf2 knockdown reversed CGA's effects. These findings suggest that CGA exerts anti-seizure and neuroprotective effects via microglial modulation through the Nrf2/HO-1 pathway.
Antinociceptive role of IL-10/STAT3 signaling in trigeminal neuropathic pain male rat model through Pomc and β-endorphin.
Perdana LP, Fabillar J, Arini DS … +6 more , Raman S, Raju R, Ikutame D, Oshima M, Miyoshi K, Matsuka Y
Neurosci Lett · 2026 Feb · PMID 41421421 · Publisher ↗
Interleukin-10 (IL-10) is a cytokine that can exert an analgesic effect on trigeminal neuropathic pain (TNP). However, its precise mechanism remains unclear. In this study, we investigated the antinociceptive effects of...
Interleukin-10 (IL-10) is a cytokine that can exert an analgesic effect on trigeminal neuropathic pain (TNP). However, its precise mechanism remains unclear. In this study, we investigated the antinociceptive effects of recombinant IL-10 (rIL-10) in a rat model of infraorbital nerve constriction. Using male Sprague-Dawley rats, we administered rIL-10 or phosphate-buffered saline to the intra-trigeminal ganglion and observed a peak analgesic effect at 4 h post-injection in the rIL-10 group. Real-time PCR demonstrated significant upregulation of the Proopiomelanocortin (Pomc) gene in rIL-10-treated rats, with immunofluorescence staining confirming increased expression of bioactive peptide β-endorphin (β-END) in the same group. In situ hybridization assay further localized Pomc expression to satellite glial cells and neurons in the trigeminal ganglion, with β-END exhibiting a similar distribution. To elucidate the signaling mechanism, we co-administered a STAT3 inhibitor, Stattic, which abolished the analgesic effect of rIL-10, suppressed Pomc upregulation, and reduced β-END expression. These findings indicate that the STAT3 pathway is a critical mediator of rIL-10-induced analgesia, with Pomc and β-END as potential molecular effectors.
Suppression of 5-HT receptor signaling impairs normal eye development in zebrafish.
Ulhaq ZS, Kishida M
Neurosci Lett · 2026 Feb · PMID 41412499 · Publisher ↗
Serotonin (5-HT) signaling plays essential roles in vertebrate development beyond neurotransmission, including in ocular morphogenesis. Here, we investigated the effects of Ritanserin, a non-selective 5-HT receptor antag...
Serotonin (5-HT) signaling plays essential roles in vertebrate development beyond neurotransmission, including in ocular morphogenesis. Here, we investigated the effects of Ritanserin, a non-selective 5-HT receptor antagonist, on zebrafish embryonic development with a focus on eye formation. While Ritanserin exposure (0.1-10 μM) did not affect mortality or hatching rates up to 96 h post-fertilization (hpf), higher concentrations (5-10 μM) induced developmental abnormalities, such as microphthalmia, pericardial edema, blood congestion, and craniofacial malformations by 5 days post-fertilization (dpf). Ritanserin significantly reduced the expression of cyp19a1b, encoding brain aromatase (AroB) involved in local estrogen synthesis within the eye, and pax6a, a key regulator of retinal neurogenesis, without altering cyp19a1a levels. Co-treatment with exogenous 5-HT or estradiol (E) partially rescued eye size, optic nerve morphology, pax6a expression, and reduced retinal apoptosis. Moreover, visual deficits induced by Ritanserin, as shown by impaired visual background adaptation (VBA) and optomotor responses (OMR), were similarly reversed by 5-HT or E. These findings demonstrate that 5-HT signaling is critical for proper eye development in zebrafish, likely through regulation of estrogen synthesis and neuroretinal gene expression, and suggest that serotonergic disruption during early development can lead to structural and functional visual deficits.
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