Neurosci. Lett. [JOURNAL]
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200 papers
Lethal yellow mutation in the Raly-Agouti locus reduces the energy expenditure in male mice.
Khotskin NV, Izyurov AE, Kulikov AV
Neurosci Lett · 2025 Oct · PMID 40912352 · Publisher ↗
The lethal yellow (A) mutation in the Raly-Agouti locus leads to ectopic expression of the agouti protein in the brain where it inhibits melanocortin receptors, causes obesity as well as alters some traits of adaptive be...
The lethal yellow (A) mutation in the Raly-Agouti locus leads to ectopic expression of the agouti protein in the brain where it inhibits melanocortin receptors, causes obesity as well as alters some traits of adaptive behavior. In the present study we used the Phenomaster calorimetric module tool to compare the travel distance, food and O consumption as well as CO excretion in 12 weeks old males of C57BL/6- A and C57BL/6 mice. The A mutation did not affect travelled distance and food consumption. At the same time, this mutation significantly reduced O consumption and CO excretion which are the main indices of indirect calorimetry. This result suggests that the reduced energy expenditure is a cause of obesity in C57BL/6- A mice. These mutant mice seem to use energy received with food in a more economical way compared to C57BL/6 mice. The results of the present study increase the impact of C57BL/6- A mice as a convenient model of neural and molecular mechanisms of economical expenditure of energy resources.
Comparative analysis of antioxidant status in Lewis and SHR inbreed rat strains.
Sell F, Pereira AG, Ramos A … +2 more , Izídio GS, Filho DW
Neurosci Lett · 2025 Oct · PMID 40907736 · Publisher ↗
The inbred rat strains Lewis (LEW) and Spontaneously Hypertensive Rats (SHR) are known for their genetically determined differences in anxiety-related behaviors and blood pressure levels. However, the relationship betwee...
The inbred rat strains Lewis (LEW) and Spontaneously Hypertensive Rats (SHR) are known for their genetically determined differences in anxiety-related behaviors and blood pressure levels. However, the relationship between these variables remains unclear, with some researchers suggesting that oxidative stress and antioxidant systems may play a crucial role in their regulation. To explore this, several oxidative stress biomarkers were evaluated in the brain and liver of both male and female LEW and SHR rats. In the brain, LEW male rats exhibited lower levels of reduced glutathione (GSH), total glutathione (GT), glutathione reductase (GR) and glutathione S-transferase (GST) activity, and higher glutathione peroxidase (GPx) activity compared to SHR males. LEW females had lower GSH, GT, catalase (CAT) and GST activity, and higher GPx activity than their SHR counterparts. Additionally, males, regardless of strain, showed lower levels of thiobarbituric acid reactive substances and GPx activity, but higher GSH levels and GT activity compared to females. Conversely, in the liver, there were no significant differences in GSH activity, but interactions between strain and sex were observed for all other biomarkers evaluated. Overall, the results indicate that LEW rats have a lower brain antioxidant capacity compared to SHR rats, while the liver data are more variable. This constitutively lower antioxidant profile in the brain of LEW rats, observed in both sexes, may be correlated with their high anxiety/emotionality behavior, when compared to the SHR rats.
Directional flow of brain connections and neurodevelopmental outcomes in healthy full-term newborns.
Chirumamilla VC, Mulkey SB, Anwar T … +7 more , Baker R, Maxwell GL, Asis-Cruz J, Kapse K, Limperopoulos C, Plessis AD, Govindan RB
Neurosci Lett · 2025 Oct · PMID 40889547 · Full text
OBJECTIVE: We examined whether directional flow among brain hubs in healthy-term infants is associated with neurodevelopmental outcomes at two years of age. METHODS: High-density electroencephalography (EEG) was collecte...
OBJECTIVE: We examined whether directional flow among brain hubs in healthy-term infants is associated with neurodevelopmental outcomes at two years of age. METHODS: High-density electroencephalography (EEG) was collected within 72 h after birth. Neurodevelopmental outcomes (cognitive, language, and motor scores) were measured using Bayley Scales of Infant Development-III (BSID-III) at two years. Source signals were extracted from the hubs, and directed information flow from hub was calculated using partial directed coherence method in delta band. The relationship between information flow and BSID-III scores was assessed using stepwise regression. RESULTS: Forty-seven newborns had EEG and BSID-III scores. Efferent flow from the left amygdala (t-statistic = -2.97, p = 0.027), right amygdala (t-statistic = -2.15, p = 0.03), and right caudate nucleus (t-statistic = -2.16, p = 0.036) were negatively associated, while the left pallidum (t-statistic = 2.72, p = 0.02) was positively associated with cognitive scores. The efferent flow from the right amygdala (t-statistic = -2.34, p = 0.03) was negatively associated with language scores, while efferent flow from the brainstem (t-statistic = 2.38, p = 0.03) was positively associated with motor scores. CONCLUSIONS: Efferent output from specific hubs at birth is associated with neurodevelopmental outcomes at two years of age.
Left-right asymmetry in the thoracic spinal cord.
Kirkwood PA
Neurosci Lett · 2025 Oct · PMID 40886764 · Publisher ↗
Evidence of left-right asymmetry in the spinal cord has been accumulating for some time. This report adds an anatomical example. For thoracic segments in the cat, the dorsal root entries of a given segment, at least for...
Evidence of left-right asymmetry in the spinal cord has been accumulating for some time. This report adds an anatomical example. For thoracic segments in the cat, the dorsal root entries of a given segment, at least for T5 to T9, were shown to have a tendency to be located more rostrally on the right than on the left. Measurements of the root positions have been brought together from notes in experimental protocols over nine years (36 animals). The rostral-most root of a segment on the right was found to lie up to 4.5 mm more rostrally than that on the left (mean 0.93 ± 1.05 mm, n = 86), while the caudal-most root was similarly asymmetric by up to 5.5 mm (mean 0.98 ± 1.72 mm, n = 30). These results are supported by very similar measurements made from the undamaged regions of spinal cords in a further 36 animals that had spinal cord lesions. Implications of the asymmetry are discussed.
Region-specific modulation and predictive potential of the oscillatory dynamics in an ex vivo model of ictogenesis in the CA1, CA3 and dentate gyrus.
Vagiaki LE, Xydias D, Kefalogianni M … +3 more , Psilodimitrakopoulos S, Stratakis E, Sidiropoulou K
Neurosci Lett · 2025 Oct · PMID 40886763 · Publisher ↗
The hippocampus, including the cornu ammonis (CA) and dentate gyrus (DG) subregions, is a brain area highly susceptible to seizure-like activity (SLA). Most studies conducted in vivo have been performed in a single hippo...
The hippocampus, including the cornu ammonis (CA) and dentate gyrus (DG) subregions, is a brain area highly susceptible to seizure-like activity (SLA). Most studies conducted in vivo have been performed in a single hippocampal subregion. In our study, we used the high [K] (HK) model of SLA to investigate the role of oscillatory activity in predicting SLA and in its modulation by anti-epileptic drugs in the three hippocampal subregions (CA1, CA3 and DG). For this, we recorded spontaneous local field potentials (LFPs) in CA1, CA3 and DG subregions from mouse hippocampal slices. We find that the oscillatory activity in the 20 s pre-ictal period is significantly different compared to the oscillatory activity in the absence of SLA or to a more distant period from the ictal event. A classification algorithm revealed that the oscillatory dynamics, particularly in the CA1 subregion, can predict the emergence of an ictal event with high accuracy. Furthermore, oscillatory activity is differentially modulated by anti-epileptic drugs in the different hippocampal subregions. We found that diazepam and carbamazepine modulated the oscillatory activity significantly greater in the CA3 and DG subregions, compared to CA1. Imaging of neuronal activation in the ex vivo model of seizure-like activity, using the Fos protein as an activity marker, revealed a similar subregion-dependent differential modulation following diazepam and carbamazepine perfusion. Therefore, while oscillatory activity in the pre-ictal period in the CA1 subregion can better predict the emergence of ictal events, anti-convulsant drugs have a stronger effect in oscillatory activity in the CA3 and DG subregions.
A novel angiotensin II type 2 receptor antagonist TDI05 alleviates the peripheral neuropathic pain.
Mao Q, Zeng Y, Liang H … +7 more , Hou S, Wang Q, Zhang J, Lan Z, Wang H, Wang J, Zhao H
Neurosci Lett · 2025 Nov · PMID 40885515 · Publisher ↗
Neuropathic pain is a debilitating chronic pain condition often associated with heightened inflammatory responses and increased angiotensin II type 2 receptor (ATR) expression. This study systematically evaluated the the...
Neuropathic pain is a debilitating chronic pain condition often associated with heightened inflammatory responses and increased angiotensin II type 2 receptor (ATR) expression. This study systematically evaluated the therapeutic efficacy of TDI05, a novel ATR antagonist, for treating neuropathic pain management. In vitro experiments using RAW 264.7 macrophages showed that TDI05 treatment significantly reduced ATR expression at both the protein and mRNA levels, as determined by Western blotting and qPCR analysis, while CCK-8 assays confirmed its non-cytotoxicity. ELISA showed TDI05 reduced the production of inflammatory mediators (TNF-α, IL-1β, IL-8) by RAW 264.7 cells. Remarkably, in co-cultured systems with HT22 neuronal cells, these anti-inflammatory effects corresponded to significant down-regulation of pain-related ion channels transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1). In vivo validation utilizing three well-established rodent neuropathic pain models, TDI05 administration produced dose-dependent analgesic effects, significantly increasing mechanical withdrawal thresholds. Furthermore, immunofluorescence staining showed TDI05 reduced ATR expression in sciatic nerve macrophages, while immunohistochemistry analysis confirmed suppression of TRPA1/TRPV1 expression in sensory neurons in the mouse spared nerve injury (SNI) model. Collectively, these findings establish TDI05 as a compelling therapeutic candidate for neuropathic pain treatment through ATR-mediated inflammatory pathway inhibition and subsequent nociceptive TRP channel inhibition.
Effects of body weight support on intermuscular coherence in triceps surae muscle during walking.
Oshima A, Hamada T, Kitamura M … +1 more , Kamibayashi K
Neurosci Lett · 2025 Oct · PMID 40865867 · Publisher ↗
The triceps surae muscle plays an important role in walking. Previous studies using coherence analysis of surface electromyography (EMG) have indicated that each muscle pair in the triceps surae [i.e., the medial head of...
The triceps surae muscle plays an important role in walking. Previous studies using coherence analysis of surface electromyography (EMG) have indicated that each muscle pair in the triceps surae [i.e., the medial head of gastrocnemius (MG)-the lateral head of gastrocnemius (LG), MG-the soleus (SOL), and LG-SOL] receives common oscillatory input during walking. Although significant intermuscular coherence (IMC) in the triceps surae muscle during normal walking has been observed in the beta and low-gamma frequency bands, it remains unclear whether IMC in these frequency bands depends on the degree of the afferent input. This study aimed to investigate whether attenuating afferent input affects IMC in the triceps surae muscle during walking. Since load-related afferent input plays an important role in neuromuscular control during walking, we focused on walking under body weight support (BWS) to modulate load-related afferent input. Fourteen healthy young adults participated in this study. The four BWS conditions were used: 100 % (no unloading), 80 %, 60 %, and 40 % of individual body weight. IMC was calculated from surface EMG in the stance phase during walking in the following three pairs: MG-LG, MG-SOL, and LG-SOL. The results showed no significant changes in IMC levels with increasing BWS levels in any frequency bands in all muscle pairs. These results suggest that common oscillatory inputs to the triceps surae muscle during walking are robust to the attenuation of load-related afferent input. The present results will contribute to a better understanding of neuromuscular control in the triceps surae muscle during walking.
Membrane fusion deficits of acutely isolated synaptic vesicles from the brains of depression-like mice.
Zhao X, Shah PT, Feng L … +7 more , Song S, Feng Y, Wu C, Liu R, Wang Y, Zhang S, Wu Z
Neurosci Lett · 2025 Oct · PMID 40865866 · Publisher ↗
Depression is a common and debilitating psychiatric disorder increasingly associated with presynaptic dysfunction, particularly impairments in synaptic vesicle (SV)-mediated neurotransmitter release, yet its underlying n...
Depression is a common and debilitating psychiatric disorder increasingly associated with presynaptic dysfunction, particularly impairments in synaptic vesicle (SV)-mediated neurotransmitter release, yet its underlying neurobiological mechanisms remain largely unresolved. In this study, we investigated SV morphology and fusion capability in a chronic variable stress (CVS)-induced mouse model of depression. To enable this analysis, we established an optimized protocol integrating differential centrifugation, density gradient ultracentrifugation, and size exclusion chromatography to isolate high-purity SVs from mouse brain tissue. Behavioral analyses confirmed the depression-like phenotype in CVS mice, characterized by anhedonia, anxiety-like behavior and behavioral despair. Although SV morphology, as characterized by TEM, appeared largely preserved, reconstituted vesicle fusion assays demonstrated a significant decline in their fusion capacity, suggesting impaired neurotransmitter release. These findings provide direct evidence of functional SV alternations in depression and underscore the key role of presynaptic dysfunction in its pathophysiology. The optimized SV isolation workflow developed in this study offers a valuable tool for investigating presynaptic mechanisms in neuropsychiatric disorders.
Computational modeling of orthodromically evoked synaptic potentials of striatal projection neurons of direct and indirect pathways.
García-Mata M, Laville A, Tapia D … +2 more , Galarraga E, Bargas J
Neurosci Lett · 2025 Oct · PMID 40865865 · Publisher ↗
Orthodromic stimulation has revealed great differences in the subthreshold and suprathreshold synaptic response kinetics of direct vs. indirect striatal projection neurons: dSPNs vs. iSPNs. Global synaptic responses of b...
Orthodromic stimulation has revealed great differences in the subthreshold and suprathreshold synaptic response kinetics of direct vs. indirect striatal projection neurons: dSPNs vs. iSPNs. Global synaptic responses of both neuron classes involve AMPA, NMDA and GABA synaptic potentials differentially distributed throughout the somatodendritic membrane. Although both responses may outlast a single initial stimulus for hundreds of milliseconds, iSPNs postsynaptic responses fire briefer action potential trains and exhibit an initial faster repolarization than those from dSPNs. Experimental evidence suggests that this divergence is due to different proportions of Ca3 (T) Ca channels in dendritic compartments, leading to a differential activation of Ca-activated K-channels, and therefore, particular contributions of synaptic inputs. In this computational work, we follow previous experimental evidence to find an efficient and minimal configuration of these currents to simulate the subthreshold and suprathreshold synaptic responses that have been reported for these neuron classes, while anatomical constraints remained constant. The Results illustrate intriguing GABAergic influences in the synaptic integration of dSPNs and iSPNs and important functional differences between the basal ganglia pathways that they originate.
HOXD4-mediated transcriptional activation of ESM1 drives glioblastoma progression in human tumor cells and mouse models.
Zhang D, Yuan Y, Wang H
Neurosci Lett · 2025 Oct · PMID 40854419 · Publisher ↗
BACKGROUND: HOXD4, a critical transcription factor (TF), is commonly overexpressed in glioblastoma (GBM). However, its functional role in GBM pathogenesis remains poorly understood METHODS: Cell phenotype alterations wer...
BACKGROUND: HOXD4, a critical transcription factor (TF), is commonly overexpressed in glioblastoma (GBM). However, its functional role in GBM pathogenesis remains poorly understood METHODS: Cell phenotype alterations were determined by measuring cell viability, invasion, migration, cycle distribution, apoptosis, and tube formation. The relationship between HOXD4 and the ESM1 promoter was verified by luciferase reporter assay. RESULTS: HOXD4 and ESM1 levels were upregulated in GBM. HOXD4 inhibition impeded GBM cell growth, invasion, and migration while enhancing apoptosis and oxidative stress, and it diminished HUVEC tube formation in vitro. HOXD4 inhibition exerted an in vivo anti-growth activity in GBM xenografts. Mechanistically, HOXD4 enhanced ESM1 transcription. Moreover, ESM1 re-expression had a counteracting impact on HOXD4 inhibition-mediated alterations of cell phenotypes. CONCLUSION: Our study demonstrates that HOXD4-mediated transcriptional activation of ESM1 enhances GBM cell malignant phenotypes and tumor angiogenesis in GBM.
Neurodegenerative features of damage to Deiters neurons in the lateral vestibular nucleus of mice after vestibular stimulation.
Mikheeva IB, Zhuikova NS, Chernomorets IY … +2 more , Pavlik LL, Arkhipov VI
Neurosci Lett · 2025 Oct · PMID 40850606 · Publisher ↗
The structure and function of the lateral vestibular nucleus (LVN), also called Deiters' nucleus, was studied in mice after 8 h of vestibular stimulation. This stimulation resulted in postural instability and movement di...
The structure and function of the lateral vestibular nucleus (LVN), also called Deiters' nucleus, was studied in mice after 8 h of vestibular stimulation. This stimulation resulted in postural instability and movement disturbances in the open field, which recovered to control levels after 48 h. The behavioral disorder was accompanied by changes in the structure of the lateral vestibular nucleus: the number of neurons decreased, their size decreased, and the number of dark neurons increased. In addition, microglial density increased 48 h after stimulation. At the ultrastructural level, significant changes occurred in Deiters neurons: a large number of lysosomes and lipofuscin granules were identified, and dramatic changes in the morphology of mitochondria were revealed. We identified two phases of increased mitophagy: one hour after vestibular stimulation and 5 days after it. If the first phase of mitophagy activation is caused by severe stress and the death of some neurons, then the second phase, in our opinion, can be caused by delayed neuroinflammation. Notably, micromitophagosomes containing fragments of cristae surrounded by a double membrane were observed within and adjacent to mitochondria. The obtained data indicate that damage to Deiters neurons after long-term vestibular stimulation has signs of neurodegeneration. The results of our work can contribute to understanding the mechanisms of movement disorders in neurodegenerative diseases.
Transcranial magnetic stimulation over right intraparietal sulcus improves selective attention for feature discriminating.
Zhang J, Song P, Hu S … +6 more , Wang X, Jia Y, Li S, Lin H, Pan N, Wang Y
Neurosci Lett · 2025 Oct · PMID 40846175 · Publisher ↗
BACKGROUND: Previous studies have confirmed the coordinated control of attentional processes by the frontal and parietal lobes. However, the function of the intraparietal sulcus (IPS) in the attention system remains uncl...
BACKGROUND: Previous studies have confirmed the coordinated control of attentional processes by the frontal and parietal lobes. However, the function of the intraparietal sulcus (IPS) in the attention system remains unclear. In this study, we measured transcranial magnetic stimulation (TMS)-evoked event-related potentials (ERPs) to determine the extent to which the right intraparietal sulcus (rIPS) is involved in attentional processing. We hypothesized that TMS potentiates the activation of the rIPS during attentional processing. METHODS: We enrolled 26 healthy participants who received single-pulse real and sham TMS at the rIPS while performing a dual-feature delayed matching task with sequential pairs of visual stimuli (S1 followed by S2). Participants were asked to discriminate whether the relevant feature of S2 was identical to S1 while ignoring the irrelevant feature. RESULTS: The results showed a shorter response time for real TMS to the rIPS compared to sham TMS in the color task. N270 amplitudes decreased during selective attentional processing. CONCLUSIONS: Single-pulse TMS to the rIPS decreases the amplitude of the N270, improving selective attention and enhancing task performance. Our results show that TMS can activate the IPS to facilitate attentional processing for feature discrimination.
Corrigendum to "Increasing indoxyl sulfate induces iNOS expression via aryl hydrocarbon receptor leading to microglia hyperactivation in the prefrontal cortex of autism-like offspring rats" [Neurosci. Lett. 862 (2025) 138298].
Miao Y, Luo R, Lin F … +7 more , Tong B, Yan J, Yang T, Sun Z, Li T, Xiao L, Chen J
Neurosci Lett · 2025 Sep · PMID 40829980 · Publisher ↗
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Tropisetron modulates the firing activity of pyramidal and fast-spiking hippocampal CA1 neurons in a mouse model of Alzheimer's disease.
Zhang T, E ED, Liu C … +3 more , Li JW, Zhong N, Zhang XQ
Neurosci Lett · 2025 Oct · PMID 40829711 · Publisher ↗
BACKGROUND: Hyperexcitability of hippocampal CA1 pyramidal neurons contributes to cognitive deficits in Alzheimer's disease (AD). Tropisetron, a 5-HT receptor antagonist and partial α7 nicotinic acetylcholine receptor (α...
BACKGROUND: Hyperexcitability of hippocampal CA1 pyramidal neurons contributes to cognitive deficits in Alzheimer's disease (AD). Tropisetron, a 5-HT receptor antagonist and partial α7 nicotinic acetylcholine receptor (α7nAChR) agonist, has shown neuroprotective effects, but its impact on hippocampal neuronal excitability remains unclear. OBJECTIVE: This study aimed to examine the effects of tropisetron on CA1 pyramidal neurons and fast-spiking interneurons in wild-type (WT) and hAPP-J20 AD model mice, a transgenic model for early-onset AD. METHODS: Whole-cell patch-clamp recordings were performed on hippocampal slices from 4-month-old WT and hAPP-J20 mice. Neuronal firing and action potential characteristics, including resting membrane potential (RMP), input resistance, threshold, amplitude and half-width were assessed with and without tropisetron. RESULTS: Pyramidal neurons in hAPP-J20 mice exhibited hyperexcitability, characterized by enhanced spike numbers, increased input resistance, and decreased RMP. Tropisetron significantly decreased their excitability accompanied by lowering action potential threshold and reducing amplitude. In contrast, tropisetron induced complex effects on fast-spiking interneurons, including a reduction in spike numbers at higher current steps, a lower action potential threshold, and a decrease in spike amplitude. CONCLUSION: Tropisetron modulates the firing activity of pyramidal and fast-spiking hippocampal CA1 neurons in hAPP-J20 mice, suggesting its potential to restore network balance and mitigate AD-related dysfunctions. These findings support further investigation into tropisetron as a therapeutic agent for AD.
Dopamine inhibits excitatory synaptic responses in layer I of the rat parasubiculum.
Carter F, Hobishi H, Chapman CA
Neurosci Lett · 2025 Oct · PMID 40818632 · Publisher ↗
The parasubiculum is a component of the hippocampal formation that projects to the entorhinal cortex and plays an important role in spatial navigation. Dopamine has marked effects on excitatory synaptic transmission in t...
The parasubiculum is a component of the hippocampal formation that projects to the entorhinal cortex and plays an important role in spatial navigation. Dopamine has marked effects on excitatory synaptic transmission in the hippocampus and entorhinal cortex, and the present study investigated the effects of dopamine on evoked field excitatory postsynaptic potentials (fEPSP) in layer I of the rat parasubiculum in vitro. Application of 50 μM dopamine for 15 min resulted in a reduction in the amplitude of fEPSPs to 71 ± 5 % of baseline that was reversed following washout of dopamine. A lower concentration of 10 μM dopamine had no effect. Application of the dopamine D-like receptor antagonist SCH23390 failed to block the reduction in fEPSP amplitude induced by dopamine, but the D-like receptor antagonist sulpiride prevented significant reductions in fEPSPs. Application of sulpiride alone facilitated fEPSP amplitude to 110 ± 3 % of baseline. These findings suggest that strong activation of dopaminergic inputs to the parasubiculum likely results in reduced excitatory synaptic activation of parasubicular neurons which may attenuate activity in their outputs to the entorhinal cortex.
Manipulation of bladder contraction by cell-type selective optogenetics of the anterior cingulate cortex neurons in a mouse model with increased urinary frequency.
Shimura H, Manita S, Mochizuki T … +7 more , Kira S, Sawada N, Bito H, Sakimura K, Takeda M, Kitamura K, Mitsui T
Neurosci Lett · 2025 Oct · PMID 40803548 · Publisher ↗
Optogenetics is a powerful technique for both investigating the mechanism underlying neurological disorders and modifying them using disease model animals. However, there is limited evidence demonstrating the potential o...
Optogenetics is a powerful technique for both investigating the mechanism underlying neurological disorders and modifying them using disease model animals. However, there is limited evidence demonstrating the potential of optogenetics in disease (lower urinary tractdysfunction; LUTD) model with targetingthe cerebral cortex.Here, we evaluated the effect of optogenetic stimulation of GABAergic neurons intheanterior cingulate cortex (ACC) on urodynamics in a urinary frequency mouse model. Channelrhodopsin-2 (ChR2) was selectively expressed in parvalbumin expressing neurons of the ACC in mice. For the induction of urinary frequency, 0.1% acetic acid was perfused into the bladder, while normal saline was used for control. Photostimulation was delivered to the ACC and intercontraction intervals (ICIs) were measured before, during and after photostimulation. Photostimulation prolonged ICI only during stimulation and ICI was recovered after stimulation in control condition. We found in the urinary frequency model that photostimulation also significantly prolonged ICI, which was recovered after stimulation. Cell-type selective photoactivation in the ACC can modulate urodynamics in disease model. The application of optogenetics for the treatment of LUTD have an advantage of temporal specificity, making it useful for controlling immediate urgency.
Arbutin improves spatial learning and memory in a lipopolysaccharide-induced neuroinflammation model via attenuating of astrocytes activation and oxidative stress.
Pouramir A, Nosratiyan N, Askari H … +3 more , Ghasemi-Kasman M, Shirzad M, Pouramir M
Neurosci Lett · 2025 Oct · PMID 40803547 · Publisher ↗
Neuroinflammation has a key role in neurodegenerative disorders and can be mimicked by systemic administration of lipopolysaccharide (LPS), which impairs cognitive function and hippocampal structure. This study examined...
Neuroinflammation has a key role in neurodegenerative disorders and can be mimicked by systemic administration of lipopolysaccharide (LPS), which impairs cognitive function and hippocampal structure. This study examined the neuroprotective effects of arbutin, a natural hydroquinone glycoside, in LPS-induced mouse model of neuroinflammation. Twenty-eight NMRI mice were divided into four groups: control, LPS, arbutin 25 mg/kg + LPS, and arbutin 50 mg/kg + LPS. Morris water maze behavioral assessment revealed that LPS significantly increased escape latency (P = 0.005) and distance explored (P = 0.003). Arbutin treatment significantly changed these effects at both doses, with 50 mg/kg showing higher efficacy (P = 0.009 vs. 25 mg/kg, P = 0.02). Histopathological analyses showed a remarkable decrease in the number of damaged neurons in CA1 and CA3 regions in arbutin-treated groups (P < 0.001), with increased NeuN-positive neurons (P < 0.05). Astrocyte reactivity, evaluated by GFAP immunostaining, was significantly suppressed by arbutin in both regions, specifically at 50 mg/kg (CA1: P = 0.0006; CA3: P = 0.0188). Oxidative stress assays demonstrated that arbutin preserved total antioxidant capacity (P = 0.0091) and reduced lipid peroxidation (P < 0.0001). Collectively, these findings indicate that arbutin mitigates LPS-induced cognitive impairment and neuroinflammation through antioxidant, anti-inflammatory, and neuroprotective mechanisms in a dose-dependent manner, supporting its potential as a supplementary therapeutic agent for neuroinflammatory manifestations.
DOPAnization of α-synuclein exacerbates dopaminergic neurodegeneration in the substantia nigra.
Togawa K, Matsumoto S, Deng L … +3 more , Jin M, Itoh Y, Hirotsune S
Neurosci Lett · 2025 Oct · PMID 40803546 · Publisher ↗
Parkinson's disease (PD) is characterized by the selective and progressive loss of dopaminergic (DAergic) neurons in the substantia nigra (SN). Although abnormal forms and aggregates of the α-synuclein (αSyn) protein are...
Parkinson's disease (PD) is characterized by the selective and progressive loss of dopaminergic (DAergic) neurons in the substantia nigra (SN). Although abnormal forms and aggregates of the α-synuclein (αSyn) protein are considered to cause PD, the underlying mechanisms of the preferential death of dopaminergic neurons are largely unknown. We recently reported that a tyrosine hydroxylase post-translationally converted a tyrosine residue of αSyn to dihydroxyphenylalanine (DOPA), termed DOPAnization, in the DAergic neurons of PD patients, which facilitated the formation of αSyn oligomers and increased neuronal toxicity in vitro. However, whether DOPAnized αSyn promotes the progressive death of DAergic neurons in vivo has not been determined. Here, we report that intranigral administration of in vitro-prepared DOPAnized αSyn oligomers induced more severe and progressive neurodegeneration in DAergic neurons than did the administration of unmodified αSyn aggregates. We also found that DOPAnized αSyn oligomers enhanced microglial activation, preceding the severe loss of SN neurons and their nigrostriatal projections. These findings suggest that DOPAnized αSyn in DAergic neurons plays a key role in the pathogenesis of PD.
Takens' theorem to assess EEG traces: Regional variations in brain dynamics.
Tozzi A, Jaušovec K
Neurosci Lett · 2025 Oct · PMID 40789435 · Publisher ↗
Takens' theorem (TT) proves that the behaviour of a dynamical system can be effectively reconstructed within a multidimensional phase space. This offers a comprehensive framework for examining temporal dependencies, dime...
Takens' theorem (TT) proves that the behaviour of a dynamical system can be effectively reconstructed within a multidimensional phase space. This offers a comprehensive framework for examining temporal dependencies, dimensional complexity and predictability of time series data. We applied TT to investigate the physiological regional differences in EEG brain dynamics of healthy subjects, focusing on three key channels: FP1 (frontal region), C3 (sensorimotor region), and O1 (occipital region). We provided a detailed reconstruction of phase spaces for each EEG channel using time-delay embedding. The reconstructed trajectories were quantified through measures of trajectory spread and average distance, offering insights into the temporal structure of brain activity that traditional linear methods struggle to capture. Variability and complexity were found to differ across the three regions, revealing notable regional variations. FP1 trajectories exhibited broader spreads, reflecting the dynamic complexity of frontal brain activity associated with higher cognitive functions. C3, involved in sensorimotor integration, displayed moderate variability, reflecting its functional role in coordinating sensory inputs and motor outputs. O1, responsible for visual processing, showed constrained and stable trajectories, consistent with repetitive and structured visual dynamics. These findings align with the functional specialization of different cortical areas, suggesting that the frontal, sensorimotor and occipital regions operate with autonomous temporal structures and nonlinear properties. This distinction may have significant implications for advancing our understanding of normal brain function and enhancing the development of brain-computer interfaces. In sum, we demonstrated the utility of TT in revealing regional variations in EEG traces, underscoring the value of nonlinear dynamics.
Inhibition of calcium-sensing receptor by its antagonist protects dopaminergic neurons from MPTP/MPP-induced neurotoxicity via regulating mitochondrial function, autophagy, and apoptosis in vivo and in vitro.
Qi H, Shen D, Wang H … +2 more , Sang W, Jiang C
Neurosci Lett · 2025 Oct · PMID 40789434 · Publisher ↗
Parkinson's disease (PD) is characterized by progressive degeneration of dopaminergic neurons. The role of calcium-sensing receptor (CaSR) in the pathogenesis of PD remains poorly understood. We employed the CaSR antago...
Parkinson's disease (PD) is characterized by progressive degeneration of dopaminergic neurons. The role of calcium-sensing receptor (CaSR) in the pathogenesis of PD remains poorly understood. We employed the CaSR antagonist NPS-2143 in bothin vivoandin vitroexperiments to investigate the therapeutic potential of CaSR modulation. Our findings revealed that MPTP/MPP exposure significantly upregulated CaSR expression. Functionally, CaSR overexpression exacerbated intracellular Ca dyshomeostasis under MPTP/MPP toxicity. Inhibition of CaSR with NPS-2143 demonstrated marked neuroprotection, evidenced by improved motor function and preservation of dopaminergic neurons in MPTP-treated mice, alongside reduced cellular apoptosis in MPP-injured MN9D cells. Mechanistically, NPS-2143 enhanced autophagy in MPP-exposed cells while reversing 3-MA-induced autophagy suppression. Furthermore, NPS-2143 mitigated mitochondrial dysfunction, as shown by reduced reactive oxygen species accumulation, restored mitochondrial membrane potential, and normalized ATP production in MPP-treated cells. These results collectively demonstrate that CaSR antagonism protects dopaminergic neurons through coordinated regulation of mitochondrial homeostasis, autophagic flux, and apoptotic pathways. Our study highlights CaSR as a promising therapeutic target for PD prevention and identifies NPS-2143 as a potential neuroprotective agent targeting CaSR.
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