European Journal of Neuroscience最新文献

Migraine, a common neurological disorder affecting about 15% of the global population, severely impacts quality of life and poses a significant economic burden. While the exact causes of migraine remain unclear, factors like oxidative stress, neurogenic inflammation, mitochondrial dysfunction, and gut dysbiosis are implicated. Through the gut–brain axis, the gut microbiota appears to play a key role in migraine pathophysiology. Patients with migraine often exhibit gastrointestinal comorbidities, and experimental studies indicate that dysbiosis can worsen migraine-like pain by amplifying inflammation and disrupting gut barrier integrity. This narrative review aims to assess the effects of probiotics, prebiotics, and synbiotics on migraine attack frequency and severity, focusing on their role in modulating gut microbiota. Evidence suggests probiotics may reduce migraine frequency and severity by enhancing gut barrier function and regulating inflammation. Prebiotics, through the improvement of gut eubiosis, may also help alleviate symptoms. However, the effects of probiotics are strain and dose dependent, leading to inconsistent findings. Studies on prebiotics and synbiotics are limited but indicate potential benefits in reducing migraine symptoms. Despite promising findings, the current literature presents mixed results regarding the effectiveness of probiotics on migraine, highlighting the importance of strain specificity and dosage. The limited number of studies on prebiotics and synbiotics, along with the variability in study designs, strains, dosages, and patient populations, complicates the ability to draw definitive conclusions. Further well-designed clinical trials are needed to elucidate the role of gut microbiota interventions in migraine management and to determine the optimal conditions for their therapeutic use.

The psychedelic psilocybin has gained popularity in recent years as a therapy for treatment-resistant depression and has been reported to reduce symptoms of depression and anxiety. Psilocybin's active metabolite, psilocin, possesses a binding affinity for serotonin receptors as well as for the serotonin transporter (5-HTT). We recently reported that in contrast to wild-type mice, psilocybin did not induce hyperlocomotion and head-twitch responses in mice genetically lacking 5-HTT, suggesting an involvement of 5-HTT in mediating these effects. To further assess the specific role of 5-HTT in psilocybin's acute behavioural effects, we treated C57BL/6 mice with the highly selective 5-HTT inhibitor escitalopram (2.5–5 mg/kg, i.p.) prior to psilocybin administration (1 mg/kg, i.p.), and measured acute behavioural effects including head-twitch response and locomotor activity. We found that acute psilocybin administration increased locomotor activity and induced head twitches, and that escitalopram did not alter these effects. Our study using low doses of escitalopram reveals no direct involvement of 5-HTT in mediating the acute effects of psilocybin in mice, and instead suggests that developmental changes and varying serotonin levels may rather explain the absence of psilocybin's acute behavioural effects previously reported in the 5-HTT homozygous knockout mice.

Pupil dilation (PD) is more pronounced during the correct recognition of previously encountered target items than during the correct rejection of novel, previously unseen foils. This phenomenon, known as the pupil old/new effect, has been interpreted in several ways—one prominent account suggests that it reflects a bottom-up attentional orienting response triggered by activated mnemonic information. Given that the magnitude of an orienting response to a stimulus is influenced by its task relevance, we tested in two experiments whether task instructions modulate the pupil old/new effect. Participants were presented with previously encoded material intermixed with novel items and were instructed to categorize the items as animate/inanimate (nonmnemonic task) and then to make an old/new recognition judgment on a subset of the items (mnemonic task). When the items had strong memory representations, an old/new effect emerged in the nonmnemonic task condition (i.e., when no explicit memory decision was required). In contrast, this effect could not be consistently demonstrated for weakly encoded items. Moreover, when the encoded stimuli were not overlearned, the old/new effect was more pronounced in the mnemonic than in the nonmnemonic task, suggesting that the effect is driven by attentional orientation modulated by task relevance. The pattern of our results thus suggests that strong memory representations can automatically trigger increased PD (i.e., without explicit memory instruction), and that the pupil old/new effect reflects an attentional orienting response toward activated mnemonic information.

The temporal and spatial characteristics of the nociceptive system have been previously investigated to understand pain mechanisms. One way to evaluate the combined temporospatial integration of sensory information is by directional discrimination. Since directional discrimination is a perceptual ability, it may be improved through perceptual learning. Perceptual learning improves the ability to perceive and recognize stimuli through practice but has rarely been investigated in the nociceptive system. The aim of this study was to investigate if perceptual learning affects nociceptive directional discrimination using moving temperature-controlled laser stimuli. Twenty-eight healthy subjects participated in a crossover study on two different days. On each day, subjects went through either supervised (i.e., with feedback) or unsupervised (i.e., without feedback) training to discriminate the direction of the moving stimulus in the right forearm. The noxious stimulus was displaced across the skin in four directions (distal, proximal, lateral, and medial) and five different displacement lengths. The subjects had to indicate the perceived stimulus direction and the degree of certainty in the discriminated direction. The results showed that there was a significant increase in the correctness of the indicated directions and certainty following supervised training. In the lateral–medial direction, the supervised training decreased the directional discrimination threshold (DDT, where 50% of directions were correctly discriminated), which was not observed for the unsupervised training. In conclusion, it was found that only supervised training improves the performance of directional discrimination. While the percentage of correct answers increased following supervised training, the estimated DDT did not decrease in all directions.