Biology subjects

Bellesi, M.

Publications and source records attributed to Bellesi, M..

9 recordsLinked to original sources

bioRxiv2026

Are infraslow oscillations the missing link between sleep and Alzheimer's?

INTRODUCTIONLocus coeruleus and glymphatic dysfunction are linked both to Alzheimers disease (AD) and, recently, to infraslow oscillation in sleep spindle (sigma) activity (ISO). Here we hypothesise ISO integrity is a critical link between sleep and AD. METHODSWe analyzed non-rapid eye movement sleep EEG from AD and controls, extracting ISO peak amplitude, intrinsic frequency, and bandwidth from the sigma-power time course. We assessed group differences and correlations with plasma biomarkers (A{beta}42/40, pTau181 and 217, NfL, GFAP). RESULTSISO peak amplitude was significantly reduced in AD, while intrinsic frequency and bandwidth were preserved. ISO peak amplitude positively correlated with A{beta}42/40 ratio, and ISO bandwidth correlated with GFAP and NfL levels, and with lower verbal memory retention. DISCUSSIONSuch selective weakening of ISO in AD is consistent with LC dysfunction and impaired glymphatic cycling. ISO may be a novel mechanism and electrophysiological marker linking sleep microarchitecture to AD pathology.

neuroscience↗

bioRxiv2025

The semantics of dreams

Dreams are universal yet deeply personal experiences. While memory and personal concerns influence dream content, the impact of other individual, generalizable traits remains poorly understood. To address this gap, we built a multimodal dataset including dream and wakefulness reports, alongside demographic, psychometric, cognitive, and sleep-related measures in a large adult cohort. Natural language processing characterized the semantic features that quantitatively distinguish dream from wakefulness reports, with this distinction significantly modulated by individual-specific factors. Longitudinal and cross-sample analyses further demonstrated that major external events, such as the COVID-19 pandemic, affect dream content, leaving lasting traces. Overall, the findings highlight a dynamic interplay between stable individual traits and external events in shaping dream experiences, offering novel insights into the cognitive and emotional architecture of dreaming.

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bioRxiv2024

Enhancing sleep via rocking ameliorates motor behavior and reduces beta-amyloid levels in a mouse model of Alzheimer's disease

Alzheimers disease (AD) is a progressive neurodegenerative disorder associated with cognitive decline and characterized by beta-amyloid plaque and tau tangle pathology. Recent research indicates a bidirectional relationship between AD pathology and sleep disturbances, with disrupted sleep exacerbating AD progression through increased beta-amyloid and tau accumulation. This strongly indicates that improving sleep may exert a direct protective effect on preventing the accumulation and spreading of AD pathology, and possibly slow the cognitive decline. Here we investigated the effects of enhancing sleep via vestibular stimulation (rocking) on AD progression in a 3xTg mouse model. Over a four-month period starting in early adulthood (p60), we monitored sleep patterns, motor function, memory, and AD pathology. Twelve-hour rocking during the light period significantly increased non-rapid eye movement (NREM) sleep duration in mice, although this effect diminished over time due to habituation. Despite this, rocking attenuated motor function decline and reduced beta-amyloid levels in the cerebral cortex of treated mice. No noticeable changes in tau levels were observed following sleep enhancement. In conclusion, our findings highlight the potential of non-pharmacological methods to enhance NREM sleep and modify disease trajectory in AD models, emphasizing the critical role of sleep in neuroprotection.

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bioRxiv2024

The individual determinants of morning dream recall

Evidence suggests that (almost) everyone dreams during their sleep and may actually do so for a large part of the night. Yet, dream recall shows large interindividual variability. Understanding the factors that influence dream recall is crucial for advancing our knowledge regarding dreams origin, significance, and functions. Here, we tackled this issue by prospectively collecting dream reports along with demographic information and psychometric, cognitive, actigraphic, and electroencephalographic measures in 204 healthy adults (18-70 y, 113 females). We found that attitude towards dreaming, proneness to mind wandering, and sleep patterns are associated with the probability of reporting a dream upon morning awakening. The likelihood of recalling dream content was predicted by age and vulnerability to interference. Moreover, dream recall appeared to be influenced by night-by-night changes in sleep patterns and showed seasonal fluctuations. Our results provide an account for previous observations regarding inter- and intra-individual variability in morning dream recall.

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bioRxiv2023

Sleep loss impairs myelin function by altering cholesterol metabolism in oligodendroglia

The increasing prevalence of sleep deprivation in modern society demands comprehension of the biological consequences of sleep loss on brain functioning. Our study reveals significant effects of sleep deprivation on myelin integrity. As a result, we identify increased conduction delays in nerve signal propagation, hindered interhemispheric synchronization, and impaired motor performance associated with sleep loss. By profiling oligodendrocyte transcriptome and lipidome, we observe sleep loss-induced endoplasmic reticulum stress and lipid metabolism disruption, particularly affecting cholesterol homeostasis. This shift in cholesterol levels alters myelin physical properties. Boosting cholesterol transport to myelin sheaths prevents sleep loss effects on nerve signal propagation and behavior. Our findings highlight the critical role of oligodendrocyte cholesterol regulation in behavioral deficits associated with sleep loss and unveil a novel target for intervention.

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bioRxiv2023

Adolescent chronic sleep restriction promotes alcohol drinking in adulthood: evidence from epidemiological and preclinical data.

Epidemiological investigations have indicated that insufficient sleep is prevalent among adolescents, posing a globally underestimated health risk. Sleep fragmentation and sleep loss during adolescence have been linked to concurrent emotional dysregulation and an increase in impulsive, risk-taking behaviors, including a higher likelihood of substance abuse. Among the most widely used substances, alcohol stands as the primary risk factor for deaths and disability among individuals aged 15-49 worldwide. While the association between sleep loss and alcohol consumption during adolescence is well documented, the extent to which prior exposure to sleep loss in adolescence contributes to heightened alcohol use later in adulthood remains less clearly delineated. Here, we analyzed longitudinal epidemiological data spanning 9 years, from adolescence to adulthood, including 5497 participants of the Avon Longitudinal Study of Parents And Children cohort. Sleep and alcohol measures collected from interviews and questionnaires at 15 and 24 years of age were analyzed with multivariable linear regression and a cross-lagged autoregressive path model. Additionally, we employed a controlled preclinical experimental setting to investigate the causal relationship underlying the associations found in the human study and to assess comorbid behavioral alterations. Preclinical data were collected by sleep restricting Marchigian Sardinian alcohol preferring rats (msP, n=40) during adolescence and measuring voluntary alcohol drinking concurrently and in adulthood. Polysomnography was used to validate the efficacy of the sleep restriction procedure. Behavioral tests were used to assess anxiety, risky behavior, and despair. In humans, after adjusting for covariates, we found a cross-sectional association between all sleep parameters and alcohol consumption at 15 years of age but not at 24 years. Notably, alcohol consumption (Alcohol Use Disorder Identification Test for Consumption) at 24 years was predicted by insufficient sleep at 15 years whilst alcohol drinking at 15 years could not predict sleep problems at 24. In msP rats, adolescent chronic sleep restriction escalated alcohol consumption and led to increased propensity for risk-taking behavior in adolescence and adulthood. Our findings demonstrate that adolescent insufficient sleep causally contributes to higher adult alcohol consumption, potentially by promoting risky behavior.

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bioRxiv2022

Ultrastructural effects of sleep and wake on the parallel fiber synapses of the cerebellum

Multiple evidence in rodents shows that the strength of excitatory synapses in the cerebral cortex and hippocampus is greater after wake than after sleep. The widespread synaptic weakening afforded by sleep is believed to keep the cost of synaptic activity under control, promote memory consolidation, and prevent synaptic saturation, thus preserving the brains ability to learn day after day. The cerebellum is highly plastic and the Purkinje cells, the sole output neurons of the cerebellar cortex, are endowed with a staggering number of excitatory parallel fiber synapses. However, whether these synapses are affected by sleep and wake is unknown. Here we used serial block face scanning electron microscopy to obtain the full 3D reconstruction of more than 7,000 spines and their parallel fiber synapses in the mouse posterior vermis. We find that most Purkinje cell spines carry a synapse, but some do not. The latter, which we call "naked" spines, are [~]5% of all spines after wake but grow to [~]10% of all spines after sleep. Further analysis shows that the changes in the number of naked synapses with wake and sleep can be accounted for by a change in the number of "branched" synapses, which are housed in two or more spines sharing the same neck. Thus, during sleep branched spines may lose one or more synapses or convert to single spines, while the opposite changes occur after wake. Because branched synapses almost always contact different parallel fibers, these results also suggest that during wake, coincidences of firing over parallel fibers may translate into the formation of synapses converging on the same branched spine, which may be especially effective at driving the soma of Purkinje cells. Sleep, on the other hand, may promote the pruning of branched synapses that were formed due to spurious coincidences.

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bioRxiv2019

Integrity of corpus callosum is essential for the cross-hemispheric propagation of sleep slow waves: a high-density EEG study in split-brain patients

The slow waves of NREM-sleep (0.5-4Hz) reflect experience-dependent plasticity and play a direct role in the restorative functions of sleep. Importantly, slow waves behave as traveling waves and their propagation is assumed to reflect the structural properties of white matter connections. Based on this assumption, the corpus callosum (CC) may represent the main responsible for cross-hemispheric slow wave propagation. To verify this hypothesis, here we studied a group of patients who underwent total callosotomy due to drug-resistant epilepsy. Overnight high-density (hd)-EEG recordings (256 electrodes) were performed in five totally callosotomized in-patients (CP; 40-53y, 2F), in three control non-callosotomized neurological in-patients (NP; 44-66y, 2F, 1M epileptic), and in an additional sample of 24 healthy adult subjects (HS; 20-47y, 13F). Data were inspected to select NREM-sleep epochs and artefactual or non-physiological activity was rejected. Slow waves were detected using an automated algorithm and their properties and propagation patterns were computed. For each slow wave parameter and for each patient, the relative z-score and the corresponding p-value were calculated with respect to the distribution represented by the HS-group. Group differences were considered significant only when a Bonferroni corrected P < 0.05 was observed in all the CP and in none of the NP. A regression-based adjustment was used to exclude potential confounding effects of age. Slow wave density, amplitude, slope and propagation speed did not differ across CP and HS. In all CP slow waves displayed a significantly reduced probability of cross-hemispheric propagation and a stronger inter-hemispheric asymmetry. Moreover, we found that the incidence of large slow waves tended to differ across hemispheres within individual NREM epochs, with a relative predominance of the right over the left hemisphere in both CP and HS. The absolute magnitude of this inter-hemispheric difference was significantly greater in CP relative to HS. This effect did not depend on differences in slow wave origin within each hemisphere across groups. Present results indicate that the integrity of the CC is essential for the cross-hemispheric traveling of sleep slow waves, supporting the assumption of a direct relationship between white matter structural integrity and cross-hemispheric slow wave propagation. Our findings also imply a prominent role of cortico-cortical connections, rather than cortico-subcortico-cortical loops, in slow wave cross-hemispheric synchronization. Finally, this data indicate that the lack of the CC does not lead to differences in sleep depth, in terms of slow wave generation/origin, across brain hemispheres.

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bioRxiv2017

Role of somatostatin-positive cortical interneurons in the generation of sleep slow waves

Cortical slow waves - the hallmark of NREM sleep - reflect near-synchronous OFF periods in cortical neurons. However, the mechanisms triggering such OFF periods are unclear, as there is little evidence for somatic inhibition. We studied cortical inhibitory interneurons that express somatostatin (SOM), because [~]70% of them are Martinotti cells that target diffusely layer 1 and can block excitatory transmission presynaptically, at glutamatergic terminals, and postsynaptically, at apical dendrites, without inhibiting the soma. In freely moving mice, we show that SOM+ cells can fire immediately before slow waves and their optogenetic stimulation triggers neuronal OFF periods during sleep. Next, we show that chemogenetic activation of SOM+ cells increases slow wave activity (SWA), the slope of individual slow waves, and the duration of NREM sleep; whereas their chemogenetic inhibition decreases SWA and slow wave incidence without changing time spent asleep. By contrast, activation of parvalbumin+ (PV+) cells, the most numerous population of cortical inhibitory neurons, greatly decreases SWA and cortical firing. These results indicate that SOM+ cells, but not PV+ cells, are involved in the generation of sleep slow waves. Whether Martinotti cells are solely responsible for this effect, or are complemented by other classes of inhibitory neurons, remains to be investigated.

neuroscience↗