Neurosci. Lett. [JOURNAL]
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200 papers
Dynorphinergic neuroadaptations in the islands of Calleja: implications for alcohol use disorder.
Cuozzo AM, Lepreux G, Reis DJ … +2 more , Wei G, Walker BM
Neurosci Lett · 2026 Jul · PMID 42392562 · Publisher ↗
Dysregulation of the dynorphin (DYN)/kappa-opioid receptor (KOR) system is heavily implicated in symptoms of alcohol use disorder (AUD) including negative affective-like states that can drive maladaptive behavioral regul...
Dysregulation of the dynorphin (DYN)/kappa-opioid receptor (KOR) system is heavily implicated in symptoms of alcohol use disorder (AUD) including negative affective-like states that can drive maladaptive behavioral regulation. Substantial efforts have been made towards understanding the neurobiology of DYN/KOR dysregulation; however, the role of dynorphinergic islands of Calleja (IC) within the olfactory tubercle (OT; part of the ventral striatum) remain poorly understood. Presently, adult male Wistar rats were trained to self-administer 10% alcohol, exposed to either air or alcohol vapor for eight weeks, and alcohol self-administration and 22-kHz ultrasonic vocalizations (USVs) assessed during acute withdrawal. Subsequently, brains were extracted during acute withdrawal and DYN A-like immunoreactivity was measured in the OT. Alcohol vapor-exposed rats demonstrated increased alcohol consumption and 22-kHz USVs compared to air-exposed controls. Vapor-exposed rats additionally demonstrated increased DYN A-like immunoreactivity in the IC. Moreover, the average DYN A neuron size positively correlated with the number of 22-kHz USVs in vapor exposed animals, but not in air-exposed controls. The present findings identify the IC as a novel DYN-associated region that may be recruited during alcohol dependence with enhanced DYN plasticity in the IC contributing to affective dysregulation in AUD and other neuropsychiatric conditions.
Differential vulnerability of cochlear nuclei to Lmx1 deficiency: abnormal patterning and implications for auditory circuitry.
Iskusnykh I, Yamoah EN, Chizhikov VV … +1 more , Fritzsch B
Neurosci Lett · 2026 Jun · PMID 42379263 · Publisher ↗
Precise regulation of progenitor identity is essential for the formation of functional auditory circuits. Cochlear nuclei arise from two major progenitor populations: Atoh1-expressing progenitors generate excitatory glut...
Precise regulation of progenitor identity is essential for the formation of functional auditory circuits. Cochlear nuclei arise from two major progenitor populations: Atoh1-expressing progenitors generate excitatory glutamatergic neurons, while Ptf1a-expressing progenitors generate inhibitory GABAergic and glycinergic neurons. Lmx1a and Lmx1b, expressed in the hindbrain roof plate, maintain Atoh1 expression in lower rhombic lip progenitors that give rise to excitatory neurons of the cochlear nuclei. Detailed analysis using dye tracing of cochlear and vestibular central projections revealed an overall reduction of input in both Lmx1a knockout mice and Lmx1a knockout mice with additonal loss of one copy of Lmx1b, although projections to the dorsal cochlear nucleus (DCN) remain relatively preserved. Dye insertion at the crossing of the acoustic stria demonstrate a progressive loss of the ventral acoustic stria (VAS) and its altered trajectory between the trigeminal and restiform body in Lmx1a and Lmx1a;Lmx1b mice. Together, these data show that the anteroventral cochlear nucleus (AVCN) is most severely affected at both embryonic and postnatal stages, showing loss and reduction of central projections. Ultimately, these findings identify Lmx1-dependent regulatory activity as a critical checkpoint for the proper development and connectivity of auditory pathways.
Role of nNOS/sGC pathway in the insular cortex in control of cardiovascular, autonomic and corticosterone responses to restraint stress in rats.
Goulart MT, Busnardo C, Belém-Filho IJA … +6 more , Fassini A, Ventris-Godoy AC, Cecílio Hallak JE, Correa FMA, Crestani CC, Alves FHF
Neurosci Lett · 2026 Jun · PMID 42372904 · Publisher ↗
The insular cortex (IC) is part of brain networks involved in physiological responses to stressful events. However, the local neurochemical mechanisms involved in the processing of stress responses by IC are still poorly...
The insular cortex (IC) is part of brain networks involved in physiological responses to stressful events. However, the local neurochemical mechanisms involved in the processing of stress responses by IC are still poorly understood. Thus, we investigated the involvement of nitrergic neurotransmission within the IC acting via neuronal isoform of nitric oxide synthase (nNOS), as well as its primary downstream target, soluble guanylate cyclase (sGC), in physiological responses during acute restraint stress, with a particular emphasis on cardiovascular and autonomic responses. For this, the selective nNOS inhibitor N(ω)propyl-L-arginine hydrochloride (NPLA, 0.04 nmol/100 nL), the NO scavenger carboxy-PTIO (1 nmol/100 nL) or the selective sGC inhibitor ODQ (1 nmol/100 nL) were bilaterally microinjected into the IC before restraint stress. We observed that the pressor and tachycardic responses to restraint were enhanced in animals treated with either NPLA, carboxy-PTIO or ODQ in the IC. Increase in circulating corticosterone during restraint was reduced in animals that received NPLA or carboxy-PTIO microinjections, but ODQ did not affect this neuroendocrine effect. Restraint-evoked drop in tail skin temperature was not affected by any of the IC pharmacological treatments. Overall, our findings provide evidence of an inhibitory influence of IC nNOS/sGC pathway in cardiovascular responses to restraint stress, whereas nNOS present within the IC is involved in corticosterone release into the circulation through sGC-independent mechanisms.
Jak1 inhibition reduces acute allodynia induced by specific upstream cytokines in rats: implications for the onset of Jak1 pain modulation.
McGaraughty S, Strasburg D, McCarthy R … +5 more , Ciura S, Kouzehgarani GN, Wilper T, Bertels Z, Housley W
Neurosci Lett · 2026 Jun · PMID 42336078 · Publisher ↗
Clinical data from patients treated with Jak1 inhibitors for diverse autoimmune diseases point to a reduction of pain at the first readouts, hinting at an action on nociceptors prior to its immunomodulatory role. Dorsal...
Clinical data from patients treated with Jak1 inhibitors for diverse autoimmune diseases point to a reduction of pain at the first readouts, hinting at an action on nociceptors prior to its immunomodulatory role. Dorsal root ganglion neurons have been shown to possess both receptors for cytokines that activate the Jak1 pathway, and Jak pathway enzymes. Cytokines that do or do not activate the Jak1 pathway and have receptors on nociceptors were administered intraplantarly to determine if these could induce a relatively quick mechanical allodynia in rats. Thus, IFNβ (300-600U), IFNα (300-600U), IL-1β (0.5-1 ng), TNFα (1-2.5 pg), and IL-6 (0.5-1 ng) evoked significant allodynia within 30 min of injection. IFNγ (1-10 ng) did not induce hind paw sensitivity. A Jak1 inhibitor, ABT-317 (1, 3, 10 mg/kg), administered 30 min prior to cytokine injection, prevented allodynia following IFNβ, IFNα, and IL-6 injections, but did not affect sensitivity after IL-1β or TNFα. The potent anti-inflammatory, prednisolone (10 mg/kg), did not affect the acute allodynia induced by IFNβ, IFNα, and IL-6 injections. ABT-317 (10 mg/kg) also reduced allodynia in a collagen arthritis model at a time when prednisolone was ineffective. ABT-317 did not modulate acute mechanical allodynia or nocifensive behaviors induced by prototypical nociceptor activators, AITC (500 µg) and capsaicin (10 µg). In addition to a well-accepted anti-inflammatory effect, the current data add to growing evidence suggesting a direct modulatory role for Jak1 inhibitors on nociceptors that can dampen pain signaling associated with specific cytokines like IL-6, IFNβ, and IFNα.
Glucocorticoids-induced depressive-like behaviors in mice: oral ingestion of corticosterone or hydrocortisone - A comparative study.
de Oliveira Torres CI, Holanda VAD, de Oliveira MC … +4 more , de Sousa-Silva AN, Moura CA, da Silva ED, Gavioli EC
Neurosci Lett · 2026 Jun · PMID 42320875 · Publisher ↗
Chronic administration of glucocorticoids is widely used to model stress-related depression in rodents. However, corticosterone, the primary endogenous glucocorticoid in rodents, is highly lipophilic and typically requir...
Chronic administration of glucocorticoids is widely used to model stress-related depression in rodents. However, corticosterone, the primary endogenous glucocorticoid in rodents, is highly lipophilic and typically requires ethanol dissolution, which may confound behavioral outcomes. Hydrocortisone (cortisol) is also detectable in mouse blood and it displays a closely related dynamics under physiological and stressful conditions to corticosterone. This study compared the behavioral effects of oral exposure to hydrocortisone hemissucinate with corticosterone (dissolved in 1% ethanol) in mice. To this aim, male Swiss mice were orally exposed for 10 days to water, hydrocortisone (0.1 mg/ml), 1% ethanol, or corticosterone (0.1 mg/ml in 1% ethanol). Body weight was daily monitored. Behavioral assessments included sucrose preference, tail suspension, splash, open field, marble burying, social interaction, and object recognition tests. Our findings showed that both glucocorticoids induced body weight loss, and reduced sucrose preference and social interaction, besides impaired memory recognition. However, 1% ethanol increased immobility in the tail suspension test and influenced body weight, thus confounding the corticosterone-related effects. Anxiety-like behaviors assessed in the exploration to the center areas of the open field, and the number of marble buried in the home cage was unaffected after chronic glucocorticoid exposure. In conclusion, hydrocortisone induced depressive-like behaviors and cognitive impairment similar to those produced by corticosterone, but without solvent-related bias. These data support the use of repeated hydrocortisone exposure in drinking water as a methodological approach to induce depressive-like phenotype in mice.
Data-driven clustering of prefrontal activation identifies functional phenotypes under prioritized dual-task walking conditions in Parkinson's disease.
Zhang X, Li W, Hu Y … +7 more , Yu Y, Lu J, Liang S, Han J, Cheng Y, Wu J, Yu N
Neurosci Lett · 2026 Jun · PMID 42314968 · Publisher ↗
BACKGROUND: Gait impairment in Parkinson's disease (PD) relates to motor-cognitive interactions, yet the specific neural characteristics patterns of different individuals under various task strategies remain unclear. Thi...
BACKGROUND: Gait impairment in Parkinson's disease (PD) relates to motor-cognitive interactions, yet the specific neural characteristics patterns of different individuals under various task strategies remain unclear. This study aimed to explore prefrontal activation heterogeneity in three prioritized dual-task walking (DTW) conditions and to identify subgroups based on neural activation characteristics, thus revealing differences in the integration of cognitive and motor resources. METHODS: Thirty-nine patients were tested during their OFF-medication state. Functional near-infrared spectroscopy (fNIRS) was used to record oxygenated hemoglobin (HbO) concentrations in the prefrontal cortex during three DTW conditions: non-prioritized (NP-DTW), motor-prioritized (MP-DTW), cognition-prioritized (CP-DTW) and single task walking. Prefrontal activation patterns were analyzed using clustering and differences between subgroups in gait, cognitive, and activation modulation capacity were compared. RESULTS: Clustering identified three subgroups: high-activity (HA), moderate-activity (MA) and low-activity group (LA). HA showed significant task modulation capacity with good gait and cognitive performance. LA, although having the lowest prefrontal activation, achieved optimal gait performance and automaticity, and superior cognition. MA showed moderate activation, but the worst gait and cognition. DTW significantly reduced gait performance, while the motor-prioritized strategy significantly mitigated gait deterioration induced by dual-tasking. CONCLUSIONS: Patients exhibit significant heterogeneity in prefrontal activation under DTW. Different activation subgroups reflect diverse functional phenotypes. Identifying subgroups based on activation characteristics aids in precision assessment and the design of personalized interventions and could inform the development of targeted rehabilitation strategies to improve patient outcomes and quality of life. TRIAL REGISTRATION: Chinese Clinical Trial Registry, www.chictr.org.cn, ChiCTR2300074453.
Antiallodynic effect of a novel sigma-1 receptor antagonist N-(1-benzylpiperidin-4-yl)-2,4-dichlorobenzamide (Dicloperidine): Synthesis and combined bioevaluation.
Navarrete-Vázquez G, Morales-Galindo DK, Ortiz-Andrade R … +6 more , Torres-Gómez H, Schepmann D, Wünsch B, Granados-Soto V, Arratia-Damian W, Déciga-Campos M
Neurosci Lett · 2026 Jun · PMID 42314967 · Publisher ↗
This study describes the synthesis and combined biological evaluation (in silico, in vitro, and in vivo) of N-(1-benzylpiperidin-4-yl)-2,4-dichlorobenzamide (Dicloperidine), a novel analogue structurally related to compo...
This study describes the synthesis and combined biological evaluation (in silico, in vitro, and in vivo) of N-(1-benzylpiperidin-4-yl)-2,4-dichlorobenzamide (Dicloperidine), a novel analogue structurally related to compound LMH-2 and haloperidol, both stablished sigma-1 receptor (σR) antagonists. Haloperidol and LMH-2 have previously demonstrated antihyperalgesic and antiallodynic effects in rat models of neuropathy induced by chronic constriction injury of the sciatic nerve and hyperglycemia. Dicloperidine was synthesized and its structure was confirmed by spectroscopic techniques. The in vitro affinity of Dicloperidine for σR was evaluated using a competitive radioligand binding assay. Dicloperidine exhibited high σR affinity (Ki = 2.6 nM), surpassing that of LMH-2 and haloperidol (Ki ≈ 6 nM). The in vivo antiallodynic activity of Dicloperidine was assessed in Wistar rats subjected to spinal nerve ligation (SNL). Its concentration-dependent antiallodynic effect at the spinal level was reversed by PRE-084, a σR agonist, thereby supporting σR antagonism as a principal mechanism underlying Dicloperidine's action. Collectively, these findings support σ1R antagonism as a potential therapeutic strategy for the management of neuropathic pain.
Embedding EEG trajectories in a Möbius-like manifold: An exploratory study.
Tozzi A
Neurosci Lett · 2026 Jun · PMID 42309345 · Publisher ↗
Time-frequency decompositions and nonlinear dynamical methods analyze electroencephalographic (EEG) signals as time series evolving in Euclidean state spaces. We explore an alternative representation of EEG dynamics in w...
Time-frequency decompositions and nonlinear dynamical methods analyze electroencephalographic (EEG) signals as time series evolving in Euclidean state spaces. We explore an alternative representation of EEG dynamics in which neural activity evolves within a Möbius-like state space. While conventional amplitude-phase descriptions represent oscillatory activity within a cylindrical state space, we additionally consider that a shift of half an oscillatory cycle reverses the sign of the waveform, transforming positive amplitudes into negative ones and vice versa. This symmetry introduces a twist into the cylindrical representation, yielding a non-orientable topology analogous to a Möbius strip in which EEG activity evolves as a continuous cyclic trajectory. Using normalized signal amplitude and instantaneous phase derived from the Hilbert transform, we reconstructed three-dimensional trajectories from EEG recordings of a healthy young adult. Our Möbius-like approach describes the geometry of the embedded EEG trajectory in terms of cyclic evolution, phase-dependent symmetry, winding number and torsion. The winding number quantifies cumulative oscillatory phase progression by measuring the number of rotations performed by the trajectory around the manifold, whereas torsion captures local changes in amplitude-phase organization by characterizing how strongly the trajectory twists in three-dimensional space. Together, these descriptors provide complementary assessment of global and local neural dynamics that are not represented by conventional EEG measures based solely on temporal, spectral or statistical properties. Potential applications include characterization of physiological and pathological brain activity, trajectory-based EEG feature extraction, integration with brain-computer interface approaches and comparative analysis of neural dynamics across cognitive and behavioral conditions.
Brain vascular structures contribute to the outflow of lymphatic vessels in the human.
Altınöz D, Özkan M, Mortaş FN … +4 more , Pirdal B, Aslıyüksek H, Çakır H, Çavdar S
Neurosci Lett · 2026 Jun · PMID 42303083 · Publisher ↗
The brain lymphatic system clears metabolic waste from neural tissue, maintains extracellular fluid homeostasis, and supports brain function. Its dysfunction is associated with neurodegenerative disorders and neuroinflam...
The brain lymphatic system clears metabolic waste from neural tissue, maintains extracellular fluid homeostasis, and supports brain function. Its dysfunction is associated with neurodegenerative disorders and neuroinflammation. Thus, lymphatic efflux is essential for brain physiology. This study evaluated the superficial and deep vascular structures involved in extracranial lymphatic drainage of the human brain. Immunohistochemistry (IHC) and Western blot analyses were used to identify LVs associated with superficial (Trolard and Labbé) and deep (internal cerebral and vein of Galen) cerebral veins and the internal jugular vein (IJV). Furthermore, the anterior (ACA), middle (MCA), internal carotid (ICA), and vertebral (VA) arteries were analyzed for LYVE-1 (a lymphatic endothelial marker) and CD31 (a vascular endothelial marker). Western blotting was used to confirm the IHC findings. The IHC analyses showed LVs in the adventitia of the vessels accompanying the ICA, VA, and IJV. However, no true LVs were observed along the ACA and MCA, nor along the superficial or deep venous structures of the brain, except the IJV. The diameters of LVs ranged from 40.1-3612.7 µm (Mean ± SD: 990.0 ± 1448.6) accompanying the ICA, 11.3-221.4 µm (Mean ± SD: 67.1 ± 72.7 µm) accompanying the VA, and 5.0-264.7 µm (Mean ± SD: 40.4 ± 61.3 µm) accompanying the IJV. Western blotting confirmed the presence of LVs accompanying the ICA, VA, and IJV. Understanding the circulation of the human brain lymphatic system can provide insights into neurological disease and new therapeutic approaches.
Genetic suppressions of CRMP2 phosphorylation ameliorate α-synuclein accumulation in an α-synucleinopathy mouse model.
Ayala Guevara V, Goshima Y, Ohshima T
Neurosci Lett · 2026 Jun · PMID 42289231 · Publisher ↗
α-synucleinopathies are a group of neurodegenerative diseases characterized by the accumulation of phosphorylated α-synuclein, forming the primary component of Lewy bodies. Current treatments can alleviate symptoms, howe...
α-synucleinopathies are a group of neurodegenerative diseases characterized by the accumulation of phosphorylated α-synuclein, forming the primary component of Lewy bodies. Current treatments can alleviate symptoms, however, there is still a lack of understanding in the mechanisms involved in the pathological processes, making difficult the development of novel therapies that can hinder the neurodegeneration. Phosphorylation of CRMP2 has previously been reported to contribute to the synaptic deficits observed in these disorders. Moreover, prior research has found increased phosphorylation of CRMP2 in DLB patients, hinting a possible involvement of CRMP2 in the pathological processes of these diseases. Therefore, in this study we used an A53T mouse model in which CRMP2 phosphorylation is prevented (A53T;CRMP2KI mice) to evaluate changes in α-synuclein accumulation and neuroinflammation. As a result, we were able to observe a reduction in phosphorylated α-synuclein (pα-synuclein) accumulation in the CA1 region of the hippocampus along with a reduction in microglia number. In addition, we were able to observe an improvement in the cognitive impairment that these mice tend to present. Taken together, these findings reaffirm the role of CRMP2 in α-synucleinopathies and suggest that CRMP2 might be a potential therapeutic target for these neurodegenerative diseases.
CCDC181, a kinocilium-localization protein, is dispensable for hair bundle development and auditory perception.
Liu C, Nahornyi R, Li J … +2 more , Oh SI, Zhao B
Neurosci Lett · 2026 Jun · PMID 42288241 · Full text
Inner ear cochlear hair cells exhibit a highly specialized ciliary architecture that consists of a bundle of stereocilia responsible for mechanotransduction and, during development, a single kinocilium that governs hair...
Inner ear cochlear hair cells exhibit a highly specialized ciliary architecture that consists of a bundle of stereocilia responsible for mechanotransduction and, during development, a single kinocilium that governs hair bundle polarity. While the morphogenesis of stereocilia is being extensively characterized and many key molecules have been identified, the molecular mechanisms governing the formation and subsequent degeneration of the kinocilium remain largely unknown. Through immunohistochemical staining, we found that CCDC181, a microtubule-binding protein, is abundantly expressed in the postnatal cochlear hair cells and specifically localized to the kinocilium. To investigate its function in cochlear hair cell morphogenesis and auditory perception, we generated a Ccdc181 knockout mouse. Hair cell morphology was characterized by using immunostaining and electron microscopy, and auditory function was then evaluated by measuring auditory brainstem responses. Our data suggests that loss of CCDC181 has minimal effects on kinocilium morphogenesis, hair cell polarity, and normal hearing in mice.
Physical restraint induces conditioned place aversion and region-specific c-Fos activation in mice.
Reinders E, Tondravi M, Lee SR … +3 more , Beyene E, Nguyen T, LeGates TA
Neurosci Lett · 2026 Jun · PMID 42270034 · Full text
Linking environmental contexts with stressful experiences is critical for engaging adaptive responses necessary to avoid future threats. Yet, active context-dependent avoidance remains poorly understood. Here, we establi...
Linking environmental contexts with stressful experiences is critical for engaging adaptive responses necessary to avoid future threats. Yet, active context-dependent avoidance remains poorly understood. Here, we establish a restraint-induced conditioned place aversion (CPA) paradigm to examine how an acute physiological stressor acquires negative motivational value through contextual association. We found that mice repeatedly exposed to physical restraint in a contextually distinguishable chamber later avoid that location, demonstrating that restraint stress can drive learned aversion in the absence of continued exposure. To identify potential neuronal correlates underlying this learned association, we quantified c-Fos expression in several areas implicated in aversive motivation, emotional salience, and contextual encoding. We found that restraint within the context of the CPA paradigm was associated with increased c-Fos in the nucleus accumbens (NAc) and basolateral amygdala (BLA) while c-Fos expression increased in the ventral hippocampus in response to exposure to the contextual cues alone. These findings reveal region-specific activation in response to restraint stress and associated contextual cues. By connecting classical stress models and associative learning, this work provides a potential platform for further investigation of the neural mechanisms underlying stress-related negative affect and avoidance behaviors.
Glycine removal from both glycinergic and glutamatergic synapses into astrocytic processes by glycine transporter 1 in the adult mouse spinal cord.
Shimizu-Okabe C, Kobayashi R, Konno T … +2 more , Ishihara Y, Takayama C
Neurosci Lett · 2026 Jun · PMID 42252052 · Publisher ↗
Glycine (Gly) and γ-aminobutyric acid (GABA) are inhibitory neurotransmitters in the spinal cord. Released Gly is removed by two Gly transporters (GlyTs): GlyT1 and GlyT2. We have previously demonstrated the localization...
Glycine (Gly) and γ-aminobutyric acid (GABA) are inhibitory neurotransmitters in the spinal cord. Released Gly is removed by two Gly transporters (GlyTs): GlyT1 and GlyT2. We have previously demonstrated the localization of GlyT2, which reuptakes Gly into presynaptic terminals. In the present study, we focused on GlyT1, which terminates glycinergic transmission by uptaking Gly into astrocytes. GlyT1 may also regulate glutamatergic transmission by controlling the concentration of Gly, which is a co-agonist of N-methyl D-aspartate receptors in the forebrain, where glycinergic synapses are sparse or absent. The immunohistochemical localization of GlyT1 was examined using a newly established GlyT1 antibody in the adult spinal cord; glycinergic, GABAergic, and glutamatergic synapses were intermingled in this region. GlyT1 was localized not only near peri-synaptic sites but also throughout astrocytic processes in the gray matter, including laminae I and II, where glycinergic terminals were sparse. GlyT1-positive honeycomb-like structures often contained GlyT2-positive glycinergic terminals. Immuno-electron microscopic analysis revealed that GlyT1-expressing astrocytic processes filled the entire interneuronal space and sealed not only inhibitory but also excitatory synapses; however, GlyT1 was not expressed in axon terminals. In addition, both GlyT1 and astrocytic GABA transporter, GAT-3, were similarly localized in the astrocytic processes. Together, these results suggest that GlyT1 expression is unrelated to glycinergic terminal density. Gly may be removed by GlyT1 from the entire interneuronal space-including glycinergic, GABAergic, and glutamatergic synaptic clefts-into astrocytic processes. Moreover, GlyT1 may regulate glutamatergic transmission via N-methyl D-aspartate receptors and might be involved in neural plasticity in the spinal cord.
BAI attenuates depression by inhibiting P2X7R and NOX2: Insights from a pharmacological animal study.
Thawkar BS, Sawant NS, Yadav H
Neurosci Lett · 2026 Jun · PMID 42250723 · Publisher ↗
The present study demonstrated that baicalin produces antidepressant effects in rats exposed to chronic unpredictable mild stress. Following stress (ST) induction, behavioural evaluations such as the forced swim test, ta...
The present study demonstrated that baicalin produces antidepressant effects in rats exposed to chronic unpredictable mild stress. Following stress (ST) induction, behavioural evaluations such as the forced swim test, tail suspension test, sucrose preference test, and open field test were used to assess BAI's efficacy. Biochemical (BC) analyses further showed that BAI administration increased key neurotransmitter levels while lowering IL-1β, P2X7 receptor, NOX2, and reactive oxygen species expression. Overall, these findings indicate that BAI effectively counteracts CUMS-induced depressive alterations at both behavioural and molecular levels, supporting its potential as an antidepressant candidate.
Prenatal alcohol exposure differently affects seizure susceptibility and severity depending on its mechanism of induction: role of excitatory synapses and parvalbumin-positive interneurons.
Dos Santos Heringer L, de Azevedo TB, Pereira Pontes TM … +3 more , Ciríaco PS, Blanco Martinez AM, Mendonça HR
Neurosci Lett · 2026 Jun · PMID 42248444 · Publisher ↗
BACKGROUND: Prenatal alcohol exposure (PAE) leads to several neurological developmental deficits, including seizure predisposition. It is speculated that alcohol would interfere with the development of GABAergic neurons,...
BACKGROUND: Prenatal alcohol exposure (PAE) leads to several neurological developmental deficits, including seizure predisposition. It is speculated that alcohol would interfere with the development of GABAergic neurons, which would fail to control neocortical excitability. METHODS: In order to test this hypothesis, we have orally exposed pregnant Swiss mice to 3 g/kg of ethanol or water daily from gestational day (G)14 until G19. At post-natal day (P)16, their offspring were submitted to analysis of seizure susceptibility and severity either by 80 mg/kg of pentylenetetrazol- or hyperthermia-provoked seizures. Subsequently, animals were euthanized and brains fixed and harvested for anatomical and immunofluorescent analyses of the number and distribution of vGluT1, parvalbumin (PV), somatostatin (SST) or vasointestinal peptide (VIP)-positive interneurons in the somatosensory cortex. RESULTS: We have found that PAE differently modulates seizures, depending on its induction mechanism: it promoted increased seizure severity after PTZ induction, but decreased seizure susceptibility after hyperthermia. Anatomical analyses revealed no alteration of cortical size. Immunofluorescence showed that PV+, but not SST+ and VIP+ interneurons, are increased in number in the somatosensory cortex, mainly in the supragranular layers. Besides, vGlut1-positive presynaptic sites were increased after PAE. DISCUSSION: These results suggest that PAE promotes increased presence of PV+ interneurons in the somatosensory neocortex, which in turn, may promote a homeostatic enhancement of excitatory circuitry to maintain E/I balance. When PTZ blocks GABAA receptors, it unmasks this enhanced excitatory circuitry, increasing seizure severity. On the other hand, when submitted to hyperthermia, the increased PV+ network protects from seizure generation, decreasing its susceptibility.
Luteolin attenuates tramadol-induced parkinsonism-like toxicity by modulating neurotransmitters, neuroinflammation, and GSK-3β signaling in rats.
Kalia N, Barik SK, Kaur R … +1 more , Singh S
Neurosci Lett · 2026 Jun · PMID 42242349 · Publisher ↗
Parkinsonism is a progressive neurodegenerative condition characterized by dopaminergic neuronal dysfunction, oxidative stress, neuroinflammation, neurotransmitter imbalance, and motor impairment. Chronic tramadol exposu...
Parkinsonism is a progressive neurodegenerative condition characterized by dopaminergic neuronal dysfunction, oxidative stress, neuroinflammation, neurotransmitter imbalance, and motor impairment. Chronic tramadol exposure has been reported to induce behavioural and neurochemical alterations resembling Parkinsonism-like neurotoxicity. The present study evaluated the neuroprotective potential of luteolin against tramadol-induced Parkinsonism-like neurotoxicity in rats using levodopa as a standard antiparkinsonian reference drug. Wistar rats were divided into five groups: normal control, tramadol (50 mg/kg, i.p.), luteolin-treated groups (50 and 100 mg/kg, p.o.), and levodopa (10 mg/kg, p.o.). Behavioural assessments were performed using Open Field, Rota Rod, and Narrow Beam Walking tests. Oxidative stress markers, inflammatory cytokines, neurotransmitter levels, and glycogen synthase kinase-3β (GSK-3β) expression were estimated, followed by histopathological evaluation of striatal tissues. Chronic tramadol administration produced significant behavioural deficits, oxidative stress, elevated inflammatory cytokines, neurotransmitter imbalance, and increased GSK-3β expression. Luteolin treatment significantly improved locomotor activity, restored antioxidant defenses, normalized neurotransmitter levels, reduced neuroinflammation, and attenuated GSK-3β expression in a dose-dependent manner. Histopathological findings further confirmed the neuroprotective effect of luteolin. These findings demonstrate that luteolin attenuates tramadol-induced neurobehavioural and neurochemical alterations through modulation of oxidative stress, neuroinflammation, neurotransmitter imbalance, and GSK-3β signaling, suggesting its therapeutic potential against Parkinsonism-like neurodegenerative alterations.
Corrigendum to "Selective upregulation of fatty acid-binding protein 5 within the basolateral amygdala blunts stress-induced reinstatement of cocaine-seeking behavior in mice" [Neurosci. Lett. 878 (2026) 138558].
Roeder N, Powell A, Hamilton J … +6 more , Richardson B, Sharma A, Sharafshah A, Blum K, Pinhasov A, Thanos PK
Neurosci Lett · 2026 Jun · PMID 42236339 · Publisher ↗
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Chronic low-dose oral methylglyoxal intake is associated with delayed circadian sleep timing and altered gut microbiota in mice.
Oishi K, Suzuki N, Takei H … +2 more , Zhuang H, Ishikawa M
Neurosci Lett · 2026 May · PMID 42217608 · Publisher ↗
Reactive carbonyls including methylglyoxal (MGO) in foodstuffs irreversibly modify proteins and generate advanced glycation end products (AGEs) that are considered toxic. On the other hand, it has also been suggested tha...
Reactive carbonyls including methylglyoxal (MGO) in foodstuffs irreversibly modify proteins and generate advanced glycation end products (AGEs) that are considered toxic. On the other hand, it has also been suggested that chronic MGO consumption does not necessarily intensify renal insufficiency or modify protein AGEs. We compared the effects of drinking water without or with 1% MGO ad libitum for approximately 9 months on sleep parameters, circadian locomotor activity, and gut microbiota in mice. Plasma AGE levels transiently increased after 3 weeks then returned to baseline. Electroencephalographic findings revealed that MGO significantly delayed the circadian phase of non-rapid eye movement (NREM) and REM sleep without affecting the total daily durations of these sleep stages. The total daily amounts and diurnal rhythms of wheel-running activity under light/dark conditions were similar between the groups, whereas MGO slightly, but not significantly extended the free-running period under constant darkness. The Firmicutes-to-Bacteroidetes ratio, a marker of gut dysbiosis, was increased >1.6-fold by MGO. Lactobacillus abundance increased >45-fold, which may reflect an adaptive microbial response to chronic MGO exposure. Thus, chronic low-dose MGO intake was associated with delayed circadian sleep onset and alterations in gut microbiota composition in mice, although a direct causal relationship between these phenomena remains unclear.
Lecanemab promotes Fc receptor-dependent cell-mediated internalization and degradation of aggregated amyloid-beta in vitro and ex vivo.
Fritz N, Johannesson M, Eriksson F … +4 more , Osswald G, Lannfelt L, Möller C, Söderberg L
Neurosci Lett · 2026 May · PMID 42214748 · Publisher ↗
Plaque deposits containing aggregated amyloid beta peptide (Aβ) fibrils are present in brain regions affected by Alzheimer's disease (AD). Lecanemab is a therapeutic monoclonal antibody that binds preferentially to solub...
Plaque deposits containing aggregated amyloid beta peptide (Aβ) fibrils are present in brain regions affected by Alzheimer's disease (AD). Lecanemab is a therapeutic monoclonal antibody that binds preferentially to soluble Aβ assemblies known as protofibrils, as well as to aggregated Aβ in amyloid plaques. Administration of lecanemab to individuals with early-stage AD reduces plaque burden and slows cognitive decline. The present study explored the role of immune cells in the mechanism of action of lecanemab using confocal microscopy, flow cytometry, and immunoassays. We show that lecanemab increases the internalization of synthetic Aβ42 protofibrils by human monocytic and mouse microglial cells, and that this effect is Fc gamma receptor-dependent. The Aβ42 protofibrils taken up by these cells were subsequently degraded within lysosomes. To investigate immune cell involvement in a system that resembled the clinical situation more closely, we evaluated the involvement of lecanemab in the removal of plaque pathology from sections of postmortem AD brain by primary human macrophages. Our results confirm that the lecanemab-mediated decrease in plaque pathology requires the presence of immune cells and is Fc gamma receptor-dependent. These data support the hypothesis that lecanemab's clinical effects involve Fc gamma receptor-dependent immune cell-mediated internalization and lysosomal degradation of Aβ protofibrils and plaques.
Itgb3 expression is developmentally regulated in pyramidal neurons of mouse cortex and hippocampus.
Cook HN, Vinson EC, Kalinowski AR … +3 more , Rodriguez HV, Denzler CJ, Vidal GS
Neurosci Lett · 2026 May · PMID 42178018 · Full text
Variants in integrin β3 (Itgb3) are associated with autism spectrum disorder and intellectual disability. Itgb3 deletion in mice leads to aberrant development of excitatory pyramidal neurons in the cerebral cortex and hi...
Variants in integrin β3 (Itgb3) are associated with autism spectrum disorder and intellectual disability. Itgb3 deletion in mice leads to aberrant development of excitatory pyramidal neurons in the cerebral cortex and hippocampus, as well as aberrant social and repetitive behaviors. However, its expression pattern in the developing brain has not been well studied. Due to its functional importance in the developing forebrain, we hypothesized that Itgb3 expression would be developmentally regulated and localized to cortical and hippocampal pyramidal neurons in the mouse brain. We found that Itgb3 mRNA is strongly expressed throughout the forebrain, especially in layer 5 of cerebral cortex and CA3 of hippocampus. In mouse cortical layer 5 and in hippocampal CA3, Itgb3 mRNA expression is high at postnatal day 6-7 and is downregulated in cortex by postnatal day 20-21. It is expressed preferentially in glutamatergic excitatory pyramidal neurons. Peak Itgb3 expression therefore coincides with the timeframe for peak dendritic formation and synaptogenesis in cortical and hippocampal glutamatergic excitatory pyramidal neurons.
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