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Rationale: Glucagon-like peptide-1 (GLP-1) receptor agonists reduce alcohol consumption in rodents and non-human primates. Semaglutide is a new long-acting GLP-1 receptor agonist, widely used in the clinic against type 2 diabetes and obesity. It is also reported to reduce alcohol intake in rodents., Objectives: This study investigates the possible inhibitory effect of semaglutide on alcohol intake in alcohol-preferring African green monkeys., Methods: We performed a vehicle-controlled study on male monkeys that had demonstrated a preference for alcohol. In the monkeys selected for voluntary alcohol drinking, alcohol consumption was measured for ten days at baseline (Monday to Friday for two weeks). During this period, the monkeys had access to alcohol 4 h per day and free access to water 24 h per day. After two weeks of baseline measurements, the monkeys were randomized to semaglutide or vehicle. Each group consisted of ten monkeys, and the two groups were balanced with respect to baseline alcohol intake. Following the baseline period, the monkeys were treated with escalating doses of semaglutide (up to 0.05 mg/kg) or vehicle subcutaneously twice weekly for two weeks during which period alcohol was not available. After uptitration, the monkeys had access to alcohol 4 h daily for 20 days (Monday to Friday for 4 weeks), and alcohol consumption was measured. During this alcohol exposure period, treatment with semaglutide (0.05 mg/kg twice weekly) or vehicle continued for three weeks followed by a one-week washout period., Results: Compared to the vehicle, semaglutide significantly reduced alcohol intake. There were no signs of emetic events or changes in water intake., Conclusions: These data demonstrate for the first time the potent effect of semaglutide in reducing voluntary alcohol intake in non-human primates and further substantiate the need for clinical trials investigating the effect of semaglutide in patients with alcohol-use disorder., (© 2024. The Author(s).)

The probabilistic topography and inter-individual variability of the pituitary gland (PG) remain undetermined. The absence of a standardized reference atlas hinders research on PG volumetrics. In this study, we aimed at creating maximum probability maps for the anterior and posterior PG in young female adults. We manually delineated the anterior and posterior parts of the pituitary glands in 26 healthy subjects using high-resolution MRI T1 images. A three-step procedure and a cost function-masking approach were employed to optimize spatial normalization for the PG. We generated probabilistic atlases and maximum probability maps, which were subsequently coregistered back to the subjects' space and compared to manual delineations. Manual measurements led to a total pituitary volume of 705 ± 88 mm³, with the anterior and posterior volumes measuring 614 ± 82 mm³ and 91 ± 20 mm³, respectively. The mean relative volume difference between manual and atlas-based estimations was 1.3%. The global pituitary atlas exhibited an 80% (± 9%) overlap for the DICE index and 67% (± 11%) for the Jaccard index. Similarly, these values were 77% (± 13%) and 64% (± 14%) for the anterior pituitary atlas and 62% (± 21%) and 47% (± 17%) for the posterior PG atlas, respectively. We observed a substantial concordance and a significant correlation between the volume estimations of the manual and atlas-based methods for the global pituitary and anterior volumes. The maximum probability maps of the anterior and posterior PG lay the groundwork for automatic atlas-based segmentation methods and the standardized analysis of large PG datasets., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Patients with Anorexia Nervosa (AN) and athletes share intense physical activity and pituitary hormonal disturbances related to absolute (AN) or relative (athletes) undernutrition. Pituitary gland (PG) structure evaluations in those conditions are scarce, and did not differentiate anterior from posterior lobe. We evaluated the structure-function relationship of anterior and posterior PG in AN and athletes, and potential reversibility of this alteration in a group of weight-recovered patients (AN&#95;Rec). Manual delineation of anterior (AP) and posterior (PP) PG was performed on T1-weighted MR images in 17 women with AN, 15 women with AN&#95;Rec, 18 athletes women and 25 female controls. Anthropometric, hormonal, and psychometric parameters were explored and correlated with PG volumes. AP volume (APV) was lower in AN (448 ± 82 mm 3 ), AN&#95;Rec (505 ± 59 mm 3 ), and athletes (540 ± 101 mm 3 ) vs. Controls (615 ± 61 mm 3 , p < 0.00001, p < 0.00001 and p = 0.02, respectively); and smaller in AN vs. AN&#95;Rec (p = 0.007). PP volume did not show any differences between the groups. APV was positively correlated with weight (R = 0.36, p = 0.011) in AN, and luteinizing hormone (R = 0.35, p = 0.014) in total group. In AN, mean growth hormone (GH) was negatively correlated with global pituitary volume (R = 0.31, p = 0.031) and APV (R = 0.29, p = 0.037). Absolute and relative undernutrition led to a decreased anterior pituitary gland volume, which was reversible with weight gain, correlated with low bodyweight, and blockade of gonadal hypothalamic-pituitary axis. Intriguing inverse correlation between anterior pituitary gland volume and GH plasma level could suggests a low storage capacity of anterior pituitary gland and increased reactivity to low insulin-like growth factor type 1., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In recent decades, numerous structural brain imaging studies investigated purported morphometric changes in early (EB) and late onset blindness (LB). The results of these studies have not yielded very consistent results, neither with respect to the type, nor to the anatomical locations of the brain morphometric alterations. To better characterize the effects of blindness on brain morphometry, we performed a systematic review and an Anatomical-Likelihood-Estimation (ALE) coordinate-based-meta-analysis of 65 eligible studies on brain structural changes in EB and LB, including 890 EB, 466 LB and 1257 sighted controls. Results revealed atrophic changes throughout the whole extent of the retino-geniculo-striate system in both EB and LB, whereas changes in areas beyond the occipital lobe occurred in EB only. We discuss the nature of some of the contradictory findings with respect to the used brain imaging methodologies and characteristics of the blind populations such as the onset, duration and cause of blindness. Future studies should aim for much larger sample sizes, eventually by merging data from different brain imaging centers using the same imaging sequences, opt for multimodal structural brain imaging, and go beyond a purely structural approach by combining functional with structural connectivity network analyses., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We perceive our surrounding environment using all of our senses in parallel, building a rich multisensory representation of space (Chebat I et al. i , 2018a; Harrar I et al. i , 2018). 21 Harrar, V., Aubin, S., Chebat, D.-R., Kupers, R. and Ptito, M.. (2018). 31 Maidenbaum, S., Chebat, D.-R., Levy-Tzedek, S. and Amedi, A.. 43 Ptito, M., Chebat, D.-R. and Kupers, R. [Extracted from the article]

For blind individuals, tactile maps are useful tools to form cognitive maps through touch. However, they still experience challenges in cognitive map formation and independent navigation. Three-dimensional (3D) tactile information is thus increasingly being considered to convey enriched spatial information, but it remains unclear if it can facilitate cognitive map formation compared to traditional two-dimensional (2D) tactile information. Consequently, the present study investigated the impact of the type of sensory input (tactile 2D vs. tactile 3D vs. a visual control condition) on cognitive map formation. To do so, early blind (EB, n = 13), late blind (LB, n = 12), and sighted control (SC, n = 14) participants were tasked to learn the layouts of mazes produced with different sensory information (tactile 2D vs. tactile 3D vs. visual control) and to infer routes from memory. Results show that EB manifested stronger cognitive map formation with 3D mazes, LB performed equally well with 2D and 3D tactile mazes, and SC manifested equivalent cognitive map formation with visual and 3D tactile mazes but were negatively impacted by 2D tactile mazes. 3D tactile maps therefore have the potential to improve spatial learning for EB and newly blind individuals through a reduction of cognitive overload. Installation of 3D tactile maps in public spaces should be considered to promote universal accessibility and reduce blind individuals' wayfinding deficits related to the inaccessibility of spatial information through non-visual means., (© 2023. The Author(s).)

The ubiquitous distribution of the classic endocannabinoid system (cannabinoid receptors CB1 and CB2) has been demonstrated within the monkey nervous system, including the retina. Transient receptor potential vanilloid type 1 (TRPV1) is a cannabinoid-like non-selective cation channel receptor that is present in the retina and binds to endovannilloids and endocannabinoids, like anandamide, 2-arachidonoylglycerol and N-arachidonoyl dopamine. Retinal expression patterns of TRPV1 are available for rodents and data in higher mammals like humans and monkeys are scarce. We therefore thoroughly examined the expression and localization of TRPV1 in the retina, at various eccentricities, of the vervet (Chlorocebus sabeus) monkey, using Western blots and immunohistochemistry. Our results demonstrate that TRPV1 is found mainly in the outer and inner plexiform layers, and in the retinal ganglion cell (RGC) layer with a higher density in the periphery. Co-immunolabeling of TRPV1 with parvalbumin, a primate horizontal cell marker, revealed a clear overlap of expression throughout the entire cell structure with most prominent staining in the cell body membrane and synaptic terminals. Furthermore, double labeling of TRPV1 and syntaxin was found throughout amacrine cells in the inner plexiform layer. Finally, double staining of TRPV1 and Brn3a allowed us to confirm its previously reported expression in the cell bodies and dendrites of RGCs. The presence of TRPV1 in the horizontal pathway suggests a function of this receptor in lateral inhibition between photoreceptors through the horizontal cells, and between bipolar cells through amacrine cells.

Despite the fact that complete visual deprivation leads to volumetric reductions in brain structures associated with spatial learning, blind individuals are still able to navigate. The neural structures involved in this function are not fully understood. Our study aims to correlate the performance of congenitally blind individuals (CB) and blindfolded sighted controls (SC) in a life-size obstacle-course using a visual-to-tactile sensory substitution device, with the size of brain structures (voxel based morphometry-VBM-) measured through structural magnetic resonance Imaging (MRI). VBM was used to extract grey matter volumes within several a-priori defined brain regions in all participants. Principal component analysis was utilized to group brain regions in factors and orthogonalize brain volumes. Regression analyses were then performed to link learning abilities to these factors. We found that (1) both CB and SC were able to learn to detect and avoid obstacles; (2) their learning rates for obstacle detection and avoidance correlated significantly with the volume of brain structures known to be involved in spatial skills. There is a similar relation between regions of the dorsal stream network and avoidance for both SC and CB whereas for detection, SC rely more on medial temporal lobe structures and CB on sensorimotor areas.

There is ongoing controversy regarding the role of rapid eye movements (EMs) during rapid eye movement (REM) sleep. One prevailing hypothesis is that EMs during REM sleep are indicative of the presence of visual imagery in dreams. We tested the validity of this hypothesis by measuring EMs in blind subjects and correlating these with visual dream content. Eleven blind subjects, of whom five were congenitally blind (CB) and six late blind (LB), and 11 matched sighted control (SC) subjects participated in this study. All participants underwent full-night polysomnography (PSG) recordings that were staged manually following American Academy of Sleep Medicine (AASM) criteria. Nocturnal EMs were detected automatically using a validated EM detector, and EM activity was represented as "EM coverage" computed as percentage of time with EM in each sleep stage. Frequency of sensory dream elements was measured in dream recall questionnaires over a 30-day period. Both blind groups showed less EM coverage during wakefulness, N1, N2 and REM sleep than did controls. CB and LB subjects did not differ in EM activity. Validation of the detector applied to blind subjects revealed an overall accuracy of 95.6 ± 3.6%. Analysis of dream reports revealed that LB subjects reported significantly more visual dream elements than did CB. Although no specific mechanisms can be revealed in the current study, the quasi absence of nocturnal EMs in LB subjects despite preserved visual dream content does not support the visual scanning of dreams hypothesis. Specifically, results suggest a dissociation between EMs and visual dream content in blind individuals., (© 2019 European Sleep Research Society.)

Among the deficits in visual processing that accompany healthy aging, the earliest originate in the retina. Moreover, sex-related differences in retinal function have been increasingly recognized. To better understand the dynamics of the retinal aging trajectory, we used the light-adapted flicker electroretinogram (ERG) to functionally assess the state of the neuroretina in a large cohort of age- and sex-matched vervet monkeys ( N = 35), aged 9 to 28 years old, with no signs of obvious ocular pathology. We primarily isolated the cone-bipolar axis by stimulating the retina with a standard intensity light flash (2.57 cd/s/m 2 ) at eight different frequencies, ranging from 5 to 40 Hz. Sex-specific changes in the voltage and temporal characteristics of the flicker waveform were found in older individuals (21-28 years-old, N = 16), when compared to younger monkeys (9-20 years-old, N = 19), across all stimulus frequencies tested. Specifically, significantly prolonged implicit times were observed in older monkeys ( p < 0.05), but a significant reduction of the amplitude of the response was only found in old male monkeys ( p < 0.05). These changes might reflect ongoing degenerative processes targeting the retinal circuitry and the cone subsystem in particular. Altogether, our findings corroborate the existing literature in humans and other species, where aging detrimentally affects photopic retinal responses, and draw attention to the potential contribution of different hormonal environments.

Fetal alcohol spectrum disorder (FASD) is a chronic debilitating condition resulting in behavioral and intellectual impairments and is considered the most prevalent form of preventable mental retardation in the industrialized world. We previously reported that 2-year-old offspring of vervet monkey ( Chlorocebus sabeus ) dams drinking, on average, 2.3 ± 0.49 g ethanol per Kg maternal body weight 4 days per week during the last third of pregnancy had significantly lower numbers of CA1 (-51.6%), CA2 (-51.2%) and CA3 (-42.8%) hippocampal neurons, as compared to age-matched sucrose controls. Fetal alcohol-exposed (FAE) offspring also showed significantly lower volumes for these structures at 2 years of age. In the present study, we examined these same parameters in 12 FAE offspring with a similar average but a larger range of ethanol exposures (1.01-2.98 g/Kg/day; total ethanol exposure 24-158 g/Kg). Design-based stereology was performed on cresyl violet-stained and doublecortin (DCX)-immunostained sections of the hippocampus. We report here significant neuronal deficits in the hippocampus with a significant negative correlation between daily dose and neuronal population in CA1 ( r 2 = 0.486), CA2 ( r 2 = 0.492), and CA3 ( r 2 = 0.469). There were also significant correlations between DCX population in the dentate gyrus and daily dose ( r 2 = 0.560). Both correlations were consistent with linear dose-response models. This study illustrates that neuroanatomical sequelae of fetal ethanol exposure are dose-responsive and suggests that there may be a threshold for this effect.

Deductive reasoning and working memory are integral parts of executive functioning and are important skills for blind people in everyday life. Despite the importance of these skills, the influence of visual experience on reasoning and working memory skills, as well as on the relationship between these, is unknown. In this study, fifteen participants with congenital blindness (CB), fifteen with late blindness (LB), fifteen sighted blindfolded controls (SbfC), and fifteen sighted participants performed two tasks of deductive reasoning and two of working memory. We found that while the CB and LB participants did not differ in their deductive reasoning abilities, the CB group performed worse than the sighted controls, and the LB group performed better than the SbfC group. Those with CB outperformed all the other groups in both of the working memory tests. Working memory is associated with deductive reasoning in all three visually impaired groups, but not in the sighted group. These findings suggest that deductive reasoning is not a uniform skill, and that it is associated with visual impairment onset, the level of reasoning difficulty, and the degree of working memory load.

The brain operates through the synaptic interaction of distant neurons within flexible, often heterogeneous, distributed systems. Histological studies have detailed the connections between distant neurons, but their functional characterization deserves further exploration. Studies performed on the corpus callosum in animals and humans are unique in that they capitalize on results obtained from several neuroscience disciplines. Such data inspire a new interpretation of the function of callosal connections and delineate a novel road map, thus paving the way toward a general theory of cortico-cortical connectivity. Here we suggest that callosal axons can drive their post-synaptic targets preferentially when coupled to other inputs endowing the cortical network with a high degree of conditionality. This might depend on several factors, such as their pattern of convergence-divergence, the excitatory and inhibitory operation mode, the range of conduction velocities, the variety of homotopic and heterotopic projections and, finally, the state-dependency of their firing. We propose that, in addition to direct stimulation of post-synaptic targets, callosal axons often play a conditional driving or modulatory role, which depends on task contingencies, as documented by several recent studies., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The endocannabinoid (eCB) system has been found in all visual parts of the central ner-vous system and plays a role in the processing of visual information in many species, including monkeys and humans. Using anatomical methods, cannabinoid receptors are present in the monkey retina, particularly in the vertical glutamatergic pathway, and also in the horizontal GABAergic pathway. Modulating the eCB system regulates normal retinal function as demonstrated by electrophysiological recordings. The characterization of the expression patterns of all types of cannabinoid receptors in the retina is progressing, and further research is needed to elucidate their exact role in processing visual information. Typical cannabinoid receptors include G-protein coupled receptor CB1R and CB2R, and atypical cannabinoid receptors include the G-protein coupled receptor 55 (GPR55) and the ion channel transient receptor potential vanilloid 1 (TRPV1). This review focuses on the expression and localization studies carried out in monkeys, but some data on other animal species and humans will also be reported. Furthermore, the role of the endogenous cannabinoid receptors in retinal function will also be presented using intraocular injections of known modulators (agonists and antagonists) on electroretinographic patterns in monkeys. The effects of the natural bioactive lipid lysophosphatidylglucoside and synthetic FAAH inhibitor URB597 on retinal function, will also be described. Finally, the potential of typical and atypical cannabinoid receptor acti-vity regulation in retinal diseases, such as age-related macular degeneration, diabetic retinopathy, glaucoma, and retinitis pigmentosa will be briefly explored.

Recent studies using full-field electroretinography (ffERG) that triggers a non-specific mass response generated by several retinal sources have attributed an important role for cannabinoid receptors in mediating vision in primates. Specific cone-mediated responses evoked through the photopic flicker ERG appear to be a better way to validate the assumption that endogenous cannabinoids modulate the cone pathway, since FAAH is mainly expressed in the vervet monkey cone photoreceptors. The aim of this study is two-fold: (1) to use the photopic flicker ERG to target the cone pathway specifically, and (2) use URB597 as a selective inhibitor of the endocannabinoid degrading enzyme Fatty Acid Amide Hydrolase (FAAH) to enhance the levels of fatty acid amides, particularly anandamide. We recorded ERGs under four different flicker frequencies (15, 20, 25, and 30 Hz) in light-adapted conditions after intravitreal injections of URB597. Our results show that intravitreal injections of URB597, compared to the vehicle DMSO, increased significantly ffERG amplitudes at 30 Hz, a frequency that solely recruits cone activity. However, at 15 Hz, a frequency that activates both rods and cones, no significant difference was found in the ERG response amplitude. Additionally, we found no differences in implicit times after URB597 injections compared to DMSO vehicle. These results support the role of molecules degraded by FAAH in cone-mediated vision in non-human primates.