Neuroscience Letters最新文献

The mesopontine tegmentum (MPT), consisting of the pedunculopontine tegmentum (PPTg) and laterodorsal tegmentum (LDTg) regulates reward and aversion via direct projections to key regions including the striatum, substantia nigra, and ventral tegmental area. Chronic alcohol consumption followed by abstinence significantly downregulates the M₄ muscarinic receptor in the dorsolateral striatum. Since cholinergic projections from the mesopontine tegmentum (MPT) provide an external source of acetylcholine to this region, it is imperative to investigate how alcohol exposure and subsequent abstinence induce molecular alterations within the cholinergic system of the mesopontine tegmentum. In this study, we first characterised PPTg and LDTg projections to the dorsal striatum in alcohol-preferring iP rats, then assessed changes to cholinergic gene expression in the MPT following long-term voluntary alcohol consumption and abstinence. Using a combined retrograde tracing and immunofluorescence approach, we demonstrate that PPTg and LDTg provide direct, bilateral cholinergic innervation to both the dorsolateral and dorsomedial striatum, with less topographical specificity than previously reported in other strains. Following six months of intermittent alcohol access, RT-qPCR revealed a transient decrease in Chrna7 expression in the LDTg that returned to baseline after 14 days abstinence, and a downregulation of Chrm4 expression in the PPTg during abstinence. Together, these findings reveal that long-term voluntary alcohol consumption reconfigures mesopontine cholinergic signalling, which may contribute to the neurobiological underpinnings of AUD. SIGNIFICANCE STATEMENT: Long-term voluntary alcohol consumption reconfigures mesopontine cholinergic signalling, which may contribute to the neurobiological underpinnings of AUD.

Background: Schizotypal personality (SP) is characterized by cognitive-perceptual disturbances, interpersonal difficulties, and disorganized behavior. We examined associations between SP traits and affect, and insula-centered neural mechanisms underlying this link.

Methods: One hundred sixty-one university students completed the Schizotypal Personality Questionnaire-Brief and the Positive and Negative Affect Schedule and underwent resting-state fMRI. Seed-based whole-brain functional connectivity (FC) analyses used bilateral ventral anterior, dorsal anterior, and posterior insula seeds. Pearson correlations and mediation analyses tested associations among SP traits, Negative Affect, and FC.

Results: Cognitive-Perceptual traits correlated positively with Negative Affect (r = 0.36, p < 0.001). FC between the right inferior parietal lobule (IPL.R) and the left ventral anterior insula (vAI.L) was positively correlated with Cognitive-Perceptual traits (r = 0.33, p < 0.001), whereas FC between the right cerebellar Crus I and the vAI.L was negatively correlated (r = -0.37, p < 0.001). FC between the right ventral anterior insula (vAI.R) and the Left Calcarine Gyrus (CAL.L) was also negative (r = -0.30, p < 0.001). vAI.L-IPL.R FC partially mediated the Cognitive-Perceptual traits-Negative Affect association (indirect effect = 0.1883, 95% bootstrap CI [0.0246, 0.4022]).

Conclusion: vAI.L-IPL.R FC partially accounts for the link between Cognitive-Perceptual traits and Negative Affect, highlighting a potential neural pathway underlying affective vulnerability in SP.

Visual aftereffects are perceptual distortions that occur after prolonged exposure to a visual stimulus. We examined zebrafish larval behaviors in response to unidirectional or bidirectional grating movement in red, green, and blue during adaptation and test phases. At the end of the test, larvae were collected to assess cone photoreceptor expression Unidirectional motion adaptation induced robust, color-dependent MAEs, with the strongest effect under red stimuli, followed by green and blue. In contrast, bidirectional adaptation abolished MAEs across all colors. General locomotor activity decreased during test phases, with unidirectional adaptation maintaining higher activity than bidirectional, particularly under red stimuli. Importantly, qRT-PCR and immunostaining revealed no changes in cone photoreceptor markers, indicating that the observed behavioral modulation occurred independently of photoreceptor expression. Together, these findings demonstrate that color selectively modulates motion perception in zebrafish larvae, with red stimuli producing the strongest motion adaptation effects, while general locomotor activity and photoreceptor expression remain largely unaffected. These behavioral patterns may arise from higher-order neural processing rather than from changes at the level of photoreceptor composition.

Background and aim: Epilepsy is a prevalent neurological disorder frequently accompanied by cognitive impairments and neuronal damage. Neuroinflammation-particularly mediated by interleukin-1β (IL-1β)-plays a critical role in epileptogenesis. Sphingosine-1-phosphate (S1P), a bioactive lipid mediator, has been implicated in neuroprotection and anti-inflammatory signaling; however, its role in epilepsy remains unclear. This study aimed to investigate the effects and underlying mechanisms of S1P in a pentylenetetrazol (PTZ)-induced mouse model of epilepsy.

Methods: Male C57BL/6 mice were administered PTZ (33 mg/kg, i.p.) every other day for a total of 15 injections to establish a seizure-kindling model. S1P (0.5 mg/mL) was administered intraperitoneally during the subsequent treatment period. Seizure activity was assessed using electroencephalographic (EEG) recordings. Cognitive function was evaluated with the Morris water maze. Hippocampal neuronal morphology was examined via Nissl staining. The expression levels of IL-1β mRNA and precursor protein in the hippocampus were measured by qRT-PCR and Western blotting, respectively.

Results: S1P treatment significantly reduced seizure frequency and amplitude, shortened seizure duration, and ameliorated EEG abnormalities in epileptic mice. In behavioral assays, S1P improved spatial learning and memory performance. Histological analysis demonstrated reduced neuronal degeneration and preservation of hippocampal architecture in S1P-treated epileptic mice. Furthermore, S1P markedly decreased hippocampal IL-1β expression at both the mRNA and protein levels.

Conclusions: S1P exerts anti-seizure and neuroprotective effects in PTZ-induced epileptic mice and attenuates IL-1β-mediated neuroinflammation. These findings suggest that the S1P-IL-1β axis may represent a promising therapeutic target for epilepsy and its associated cognitive impairments.

Taurine (2-aminoethanesulfonic acid) is a naturally abundant amino acid known to support mitochondrial stability and neuronal stress resistance; however, its role in prion peptide-induced neurotoxicity has not been established. Here, we investigated whether taurine protects neuronal cells from toxicity induced by the prion protein fragment PrP(106-126) and whether autophagic flux contributes to this effect. Using an in vitro neuroblastoma cell model, we found that taurine pretreatment restored autophagic flux, as reflected by increased LC3-II/LC3-I ratios and reduced p62 accumulation. Taurine also attenuated PrP(106-126)-induced loss of mitochondrial membrane potential and apoptotic cell death. Importantly, inhibition of autophagic degradation with chloroquine prevented these protective effects, supporting a causal role for autophagy. These findings suggest that taurine mitigates prion peptide-mediated mitochondrial dysfunction by restoring autophagic flux in neuronal cells. While limited to a single in vitro model, this study provides foundational evidence that taurine-mediated modulation of autophagy may represent a potential therapeutic avenue for protein misfolding-related neurodegenerative disorders.

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.

We aimed to determine whether chronic nicotine use, alcohol consumption, and gambling alters brain glucose metabolism. We retrospectively analyzed data from 131 healthy men who participated in health check-ups at Samsung Changwon Hospital Health Promotion Center during 2013 (baseline) and 2018 (follow-up). The health checks included a brain ¹⁸F-fluorodeoxyglucose positron emission tomography (PET), a questionnaire of tobacco use, the Alcohol Use Disorders Identification Test (AUDIT; Korean version), and the Problem Gambling Severity Index (PGSI). From brain PET scans, the mean uptake in regions-of-interest was scaled to the mean global cortical uptake by each individual, defining the standardized uptake value ratio. We established a model for tobacco use, AUDIT, and PGSI with regional SUVR as a dependent variable and tobacco use, AUDIT, and PGSI as predictors adjusted for age using Bayesian hierarchical modelling. All data were analyzed using R (The R Foundation for Statistical Computing). This study included 131 healthy males (mean age at baseline and follow-up: 43.0 ± 3.4, 48.1 ± 3.3 years, respectively). Tobacco use was negatively associated with glucose metabolism in the caudate, thalamus, cingulate, and frontal lobe, and positively associated with the cerebellum, whereas AUDIT or PGSI were not associated with regional glucose metabolism. In conclusion, tobacco use was associated with altered brain glucose metabolism in the caudate, thalamus, cingulate, frontal lobe, and the cerebellum. However, neither hazardous alcohol consumption, nor problem gambling showed any association with brain glucose metabolism. Our findings might provide new insights into the neural mechanisms of chronic nicotine use.

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.