Decreased olfactory discrimination is associated with impulsivity in healthy volunteers

In clinical populations, olfactory abilities parallel executive function, implicating shared neuroanatomical substrates within the ventral prefrontal cortex. In healthy individuals, the relationship between olfaction and personality traits or certain cognitive and behavioural characteristics remains unexplored. We therefore tested if olfactory function is associated with trait and behavioural impulsivity in nonclinical individuals. Eighty-three healthy volunteers (50 females) underwent quantitative assessment of olfactory function (odour detection threshold, discrimination, and identifcation). Each participant was rated for trait impulsivity index using the Barratt Impulsiveness Scale and performed a battery of tasks to assess behavioural impulsivity (Stop Signal Task, SST; Information Sampling Task, IST; Delay Discounting). Lower odour discrimination predicted high ratings in non-planning impulsivity (Barratt Non-Planning impulsivity subscale); both, lower odour discrimination and detection threshold predicted low inhibitory control (SST; increased motor impulsivity). These fndings extend clinical observations to support the hypothesis that defcits in olfactory ability are linked to impulsive tendencies within the healthy population. In particular, the relationship between olfactory abilities and behavioural inhibitory control (in the SST) reinforces evidence for functional overlap between neural networks involved in both processes. These fndings may usefully inform the stratifcation of people at risk of impulse-control-related problems and support planning early clinical interventions

Long-COVID cognitive impairments and reproductive hormone deficits in men may stem from GnRH neuronal death

BACKGROUND: We have recently demonstrated a causal link between loss of gonadotropin-releasing hormone (GnRH), the master molecule regulating reproduction, and cognitive deficits during pathological aging, including Down syndrome and Alzheimer's disease. Olfactory and cognitive alterations, which persist in some COVID-19 patients, and long-term hypotestosteronaemia in SARS-CoV-2-infected men are also reminiscent of the consequences of deficient GnRH, suggesting that GnRH system neuroinvasion could underlie certain post-COVID symptoms and thus lead to accelerated or exacerbated cognitive decline. METHODS: We explored the hormonal profile of COVID-19 patients and targets of SARS-CoV-2 infection in post-mortem patient brains and human fetal tissue. FINDINGS: We found that persistent hypotestosteronaemia in some men could indeed be of hypothalamic origin, favouring post-COVID cognitive or neurological symptoms, and that changes in testosterone levels and body weight over time were inversely correlated. Infection of olfactory sensory neurons and multifunctional hypothalamic glia called tanycytes highlighted at least two viable neuroinvasion routes. Furthermore, GnRH neurons themselves were dying in all patient brains studied, dramatically reducing GnRH expression. Human fetal olfactory and vomeronasal epithelia, from which GnRH neurons arise, and fetal GnRH neurons also appeared susceptible to infection. INTERPRETATION: Putative GnRH neuron and tanycyte dysfunction following SARS-CoV-2 neuroinvasion could be responsible for serious reproductive, metabolic, and mental health consequences in long-COVID and lead to an increased risk of neurodevelopmental and neurodegenerative pathologies over time in all age groups. FUNDING: European Research Council (ERC) grant agreements No 810331, No 725149, No 804236, the European Union Horizon 2020 research and innovation program No 847941, the Fondation pour la Recherche Médicale (FRM) and the Agence Nationale de la Recherche en Santé (ANRS) No ECTZ200878 Long Covid 2021 ANRS0167 SIGNAL, Agence Nationale de la recherche (ANR) grant agreements No ANR-19-CE16-0021-02, No ANR-11-LABEX-0009, No. ANR-10-LABEX-0046, No. ANR-16-IDEX-0004, Inserm Cross-Cutting Scientific Program HuDeCA, the CHU Lille Bonus H, the UK Medical Research Council (MRC) and National Institute of Health and care Research (NIHR)

Alcohol-Related Context Modulates Performance of Social Drinkers in a Visual Go/No-Go Task: A Preliminary Assessment of Event-Related Potentials

Background Increased alcohol cue-reactivity and altered inhibitory processing have been reported in heavy social drinkers and alcohol-dependent patients, and are associated with relapse. In social drinkers, these two processes have been usually studied separately by recording event-related potentials (ERPs) during rapid picture presentation. The aim of our study was to confront social drinkers to a task triggering high alcohol cue-reactivity, to verify whether it specifically altered inhibitory performance, by using long-lasting background picture presentation. Methods ERP were recorded during visual Go/No-Go tasks performed by social drinkers, in which a frequent Go signal (letter “M”), and a rare No-Go signal (letter “W”) were superimposed on three different types of background pictures: neutral (black background), alcohol-related and non alcohol-related. Results Our data suggested that heavy social drinkers made more commission errors than light drinkers, but only in the alcohol-related context. Neurophysiologically, this was reflected by a delayed No-Go P3 component. Conclusions Elevated alcohol cue-reactivity may lead to poorer inhibitory performance in heavy social drinkers, and may be considered as an important vulnerability factor in developing alcohol misuse. Prevention programs should be designed to decrease the high arousal of alcohol stimuli and strengthen cognitive control in young, at-risk individuals.This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Hyperphosphorylation and Cleavage at D421 Enhance Tau Secretion

It is well established that tau pathology propagates in a predictable manner in Alzheimer’s disease (AD). Moreover, tau accumulates in the cerebrospinal fluid (CSF) of AD’s patients. The mechanisms underlying the propagation of tau pathology and its accumulation in the CSF remain to be elucidated. Recent studies have reported that human tau was secreted by neurons and non-neuronal cells when it was overexpressed indicating that tau secretion could contribute to the spreading of tau pathology in the brain and could lead to its accumulation in the CSF. In the present study, we showed that the overexpression of human tau resulted in its secretion by Hela cells. The main form of tau secreted by these cells was cleaved at the C-terminal. Surprisingly, secreted tau was dephosphorylated at several sites in comparison to intracellular tau which presented a strong immunoreactivity to all phospho-dependent antibodies tested. Our data also revealed that phosphorylation and cleavage of tau favored its secretion by Hela cells. Indeed, the mimicking of phosphorylation at 12 sites known to be phosphorylated in AD enhanced tau secretion. A mutant form of tau truncated at D421, the preferential cleavage site of caspase-3, was also significantly more secreted than wild-type tau. Taken together, our results indicate that hyperphosphorylation and cleavage of tau by favoring its secretion could contribute to the propagation of tau pathology in the brain and its accumulation in the CSF

Fecal short-chain fatty acids predict digestive disorders in premature infants

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Fiber-type differences in masseter muscle associated with different facial morphologies

BACKGROUND: The influence of muscle forces and associated physiologic behaviors on dental and skeletal development is well recognized but difficult to quantify because of the limited understanding of the interrelationships between physiologic and other mechanisms during growth. METHODS: The purpose of this study was to characterize fiber-type composition of masseter muscle in 44 subjects during surgical correction of malocclusion. Four fiber types were identified after immunostaining of biopsy sections with myosin heavy chain-specific antibodies, and the average fiber diameter and percentage of muscle occupancy of the fiber types were determined in each of 6 subject groups (Class II or Class III and open bite, normal bite, or deepbite). A 2 × 3 × 4 analysis of variance was used to determine significant differences between mean areas for fiber types, vertical relationships, and sagittal relationships. RESULTS: There were significant differences in percentage of occupancy of fiber types in masseter muscle in bite groups with different vertical dimensions. Type I fiber occupancy increased in open bites, and conversely, type II fiber occupancy increased in deepbites. The association between sagittal jaw relationships and mean fiber area was less strong, but, in the Class III group, the average fiber area was significantly different between the open bite, normal bite, and deepbite subjects. In the Class III subjects, type I and I/II hybrid fiber areas were greatly increased in subjects with deepbite. CONCLUSIONS: Given the variation between subjects in fiber areas and fiber numbers, larger subject populations will be needed to demonstrate more significant associations between sagittal relationships and muscle composition. However, the robust influence of jaw-closing muscles on vertical dimension allowed us to conclude that vertical bite characteristics vary according to the fiber type composition of masseter muscle