Browsing by browse.metadata.contributordepartment "Anatomía Humana y Psicobiología"
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- PublicationEmbargoA computerized analysis of the entire retinal ganglion cell population and its spatial distribution in adult rats(Elsevier, 2009-01) Salinas Navarro, Manuel; Mayor Torroglosa, S.; Jiménez López, M.; Avilés Trigueros, Marcelino; Holmes, T. M.; Lund, R. D.; Villegas Pérez, M. P.; Vidal Sanz, M.; Anatomía Humana y PsicobiologíaIn adult albino (SD) and pigmented (PVG) rats the entire population of retinal ganglion cells (RGCs) was quantified and their spatial distribution analyzed using a computerized technique. RGCs were back-labelled from the optic nerves (ON) or the superior colliculi (SCi) with Fluorogold (FG). Numbers of RGCs labelled from the ON [SD: 82,818 ± 3,949, n = 27; PVG: 89,241 ± 3,576, n = 6) were comparable to those labelled from the SCi [SD: 81,486 ± 4,340, n = 37; PVG: 87,229 ± 3,199; n = 59]. Detailed methodology to provide cell density information at small scales demonstrated the presence of a horizontal region in the dorsal retina with highest densities, resembling a visual streak.
PublicationRestrictedAge-related brain pathology in Octodon degu: blood vessel, white matter and Alzheimer-like pathology(Elsevier, 2009-11-11) Van Groen, Thomas; Kadish, Inga; Popovic, Natalija; Popovic, Miroljub; Caballero Bleda, María; Baño-Otalora, Beatriz; Vivanco, Pablo; Rol, María Ángeles; Madrid, Juan Antonio; Anatomía Humana y PsicobiologíaRecently it has been shown that over 3-year-old wild-type South American rodents, Octodon degus, the "common degu" or degu, of their own accord develop Alzheimer's disease neuropathological hallmarks: amyloid-β-peptide depositions and accumulation of tau-protein. Here we analyzed brains of 1-, 3- and 6-year-old degu's, bred in standard animal facilities. Significant amounts of Aβ and tau deposits are present in the hippocampal formation of 6-year-old O. degus, primarily in the white matter, but these hippocampal Aβ and tau deposits are not present in younger ones. In contrast, significant Aβ deposits in blood vessel walls are already found in 3-year-old animals. The tau deposits in the hippocampal formation coincide with a significant decrease in staining for myelin in the same areas, indicating hippocampal disconnection and, likely, dysfunction. Our findings indicate that (1) cerebral amyloid angiopathy precedes brain parenchyma pathology in aged degu's and (2) the onset of disease seems to be delayed in the laboratory vs. wild-type degu's.- PublicationOpen AccessAnatomía clínica: Implantes cigomáticosLópez González, Laura; Anatomía Humana y Psicobiología; Facultad de Medicina
- PublicationOpen AccessAtlas de disección: guía de estudio Neuroanatomía ILópez González, Laura; Anatomía Humana y Psicobiología; Facultad de Medicina
- PublicationOpen AccessAtlas de disección: guía de estudio Neuroanatomía IILópez González, Laura; Anatomía Humana y Psicobiología; Facultad de Medicina
- PublicationOpen AccessAtlas descriptivo: Anatomía detallada de las estructuras dentales humanasLópez González, Laura; Anatomía Humana y Psicobiología
- PublicationOpen AccessAutomated quantification and topographical distribution of the whole population of S- and L-cones in adult albino and pigmented rats(Association for Research in Vision and Ophthalmology, 2010-06) Ortín Martínez, Arturo; Jiménez López, Manuel; Nadal Nicolás, Francisco M.; Salinas Navarro, Manuel; Alarcón Martínez, Lluis; Sauvé, Yves; Villegas Pérez, María Paz; Vidal Sanz, Manuel; Agudo Barriuso, Marta; Anatomía Humana y PsicobiologíaPurpose.: To quantify the whole population of S- and L-cones in the albino (Sprague-Dawley, SD) and pigmented (Piebald Virol Glaxo, PVG) rats and to study their topographical distribution within the retina. Methods.: Retinal radial sections and whole-mounted retinas were double immunodetected with antibodies against UV-sensitive and L-opsins to detect the S- and L-cones, respectively. Two automated routines were developed to quantify the whole population of S- and L-cones. Detailed isodensity maps of each cone type were generated. In both strains, the presence of dual cones was detected, these were semiautomatically quantified and their distribution determined. The matching distribution of retinal ganglion cells (RGCs) and L-cones was attained by double immunodetection of Brn3a and L-opsin, respectively Results.: The mean number ± SEM of L- or S-cones in SD and PVG retinas was 231,736 ± 14,517 and 239,939 ± 6,494 or 41,028 ± 5,074, and 27,316 ± 2,235, respectively. There was an increasing gradient of S-cone density along the inferonasal quadrant, although the highest densities were found in the retinal rims. The distribution of L-cones seemed to be complementary to the S-cones. The highest densities were observed in the superior nasotemporal axis, paralleling the distribution of Brn3a-positive RGCs. Conclusions.: These data establish, for the first time, the total number and the topographical distribution of S- and L-cones in two rat strains and demonstrate the correlation of L-cones and RGC spatial distribution.
- PublicationOpen AccessAutonomic reactivity in blood-injection-injury and snake phobia(Elsevier, 2018-12) Sánchez-Navarro JP, Juan P.; Martínez-Selva, José M.; Maldonado, Enrique F.; Carrillo-Verdejo, Eduvigis; Pineda, Sara; Torrente, Ginesa; Anatomía Humana y PsicobiologíaObjective: This research aimed to study the salivary flow and other autonomic reactions -heart rate (HR) and skin conductance response (SCR)- in blood-injection-injury (BII) phobia and snake phobia participants, under the assumption that exposure to blood-related pictures in BII phobia will provoke an increase in parasympathetic activity that, in turn, will lead to a greater saliva production than other affective contents. Methods: We selected 18 BII phobia and 14 snake phobia participants along with 22 non-phobia individuals. All participants were exposed to 3 blocks of pictures (12 pictures per block) depicting either mutilations, snakes or neutral, household objects. Saliva samples were taken in the 2-min interval before and after each block. Results: In comparison to other contents, blood-related pictures provoked an increase in salivary flow in BII phobia participants, as well as an increase in the number of SCRs. In the snake phobia group, snake pictures provoked HR acceleration, but the SCRs they elicited did not differ from the SCRs provoked by the blood-related pictures. Conclusion: BII phobia individuals react to their phobic object with a series of physiological changes resulting from a sympathetic-parasympathetic co-activation. This is in contrast with other specific phobias (e.g., small animal phobias) that usually show a sympathetically mediated, defensive reactivity when exposed to their disorder-relevant stimuli. These data support the use of therapeutic interventions in BII phobia that may differ in some respect from those used in other specific phobias.
- PublicationEmbargoBarnes maze performance of Octodon degus is gender dependent(Elsevier, 2010-04-10) Popovic, Natalija; Madrid, Juan Antonio; Rol, María Ángeles; Caballero Bleda, María; Popovic, Miroljub; Anatomía Humana y PsicobiologíaGender differences in spatial navigation have been widely reported in nocturnal rodent species. Here, for the first time we report gender differences in spatial learning and memory of Octodon degus, a long-lived diurnal hystricomorph rodent. In the present study, 16 months old male and female O. degus were tested in the 18-holes Barnes circular maze. The acquisition session consisted of four daily 4 min trials, during 10 days. Seven days later, the retention test was performed. To avoid the effect of hormonal fluctuation on spatial navigation, both the acquisition and the retention tests, were performed in 21-day regular cycling females in a period that corresponds to the diestrus phase of the estrus cycle. At the beginning of the acquisition, female degus were significantly slower than males to find the escape hole, but the situation reversed afterwards. Moreover, during the course of acquisition, females made significantly less reference memory errors, working memory errors as well as omission errors, than males. In both sexes, motivation and learning ceiling effects were reached at days 5–6 of the training. During the acquisition, females used more frequently a spatial strategy, while males preferably applied either serial, random or opposite strategies. The observed cognitive differences between male and female O. degus existed only during the acquisition period but not during the retention, indicating that acquisition and consolidation are differently influenced by gender.
- PublicationOpen AccessBidirectional gut-to-brain and brain-to-gut propagation of synucleinopathy in non-human primates(Oxford University Press, 2020-05-07) Herrero Ezquerro, María Trinidad; Arotcarena, Marie-Laure; Dovero, Sandra; Prigent, Alice; Bourdenx, Mathieu; Camus, Sandrine; Porras, Gregory; Thiolat, Marie-Laure; Tasselli, Maddalena; Aubert, Philippe; Kruse, Niels; Mollenhauer, Brit; Trigo Damas, Ines; Estrada, Cristina; Garcia-Carrillo, Nuria; Vaikath, Nishant; El-Agnaf, Omar M.A.; Vila, Miquel; Obeso, Jose A.; Derkinderen, Pascal; Dehay, Benjamin; Bezard, Erwan; Anatomía Humana y PsicobiologíaIn Parkinson’s disease, synucleinopathy is hypothesized to spread from the enteric nervous system, via the vagus nerve, to the CNS. Here, we compare, in baboon monkeys, the pathological consequences of either intrastriatal or enteric injection of a-synucleincontaining Lewy body extracts from patients with Parkinson’s disease. This study shows that patient-derived a-synuclein aggregates are able to induce nigrostriatal lesions and enteric nervous system pathology after either enteric or striatal injection in a non-human primate model. This finding suggests that the progression of a-synuclein pathology might be either caudo-rostral or rostro-caudal, varying between patients and disease subtypes. In addition, we report that a-synuclein pathological lesions were not found in the vagal nerve in our experimental setting. This study does not support the hypothesis of a transmission of a-synuclein pathology through the vagus nerve and the dorsal motor nucleus of the vagus. Instead, our results suggest a possible systemic mechanism in which the general circulation would act as a route for long-distance bidirectional transmission of endogenous a-synuclein between the enteric and the central nervous systems. Taken together, our study provides invaluable primate data exploring the role of the gut-brain axis in the initiation and propagation of Parkinson’s disease pathology and should open the door to the development and testing of new therapeutic approaches aimed at interfering with the development of sporadic Parkinson’s disease.
- PublicationEmbargoBrain injections of glial cytoplasmicinclusions induce a multiple systematrophy-like pathology(Oxford University Pres, 2022-03-14) Herrero Ezquerro, María Trinidad; Margaux, Teil; Dovero, Sandra; Bourdenx, Mathieu; Arotcarena, Marie-Laure; Camus, Sandrine; Porras, Gregory; Thiolat, Marie-Laure; Trigo-Damas, Ines; Perier, Celine; Estrada, Cristina; Garcia-Carrillo, Nuria; Morari, Michele; Meissner, Wassilios G.; Vila, Miquel; Obeso, Jose A.; Bezard, Erwan; Dehay, Benjamin; Anatomía Humana y PsicobiologíaSynucleinopathies encompass several neurodegenerative diseases, which include Parkinson’s disease, dementiawith Lewy bodies and multiple system atrophy. These diseases are characterized by the deposit ofa-synucleinaggregates in intracellular inclusions in neurons and glial cells. Unlike Parkinson’s disease and dementia withLewy bodies, where aggregates are predominantly neuronal, multiple system atrophy is associated witha-synu-clein cytoplasmic inclusions in oligodendrocytes. Glial cytoplasmic inclusions are the pathological hallmark ofmultiple system atrophy and are associated with neuroinflammation, modest demyelination and, ultimately, neu-rodegeneration.To evaluate the possible pathogenic role of glial cytoplasmic inclusions, we inoculated glial cytoplasmic inclusion-containing brain fractions obtained from multiple system atrophy patients into the striatum of non-human pri-mates. After a 2-yearin vivophase, extensive histochemical and biochemical analyses were performed on thewhole brain.We found loss of both nigral dopamine neurons and striatal medium spiny neurons, as well as loss of oligodendro-cytes in the same regions, which are characteristics of multiple system atrophy. Furthermore, demyelination, neu-roinflammation anda-synuclein pathology were also observed. These results show that thea-synuclein species inmultiple system atrophy-derived glial cytoplasmic inclusions can induce a pathological process in non-human pri-mates, including nigrostriatal and striatofugal neurodegeneration, oligodendroglial cell loss, synucleinopathy andgliosis.The present data pave the way for using this experimental model for MSA research and therapeutic development
- PublicationOpen AccessBrn3a as a marker of retinal ganglion cells: qualitative and quantitative time course studies in naïve and optic nerve–injured retinas(Association for Research in Vision and Ophthalmology, 2009-08) Nadal Nicolás, Francisco M.; Jiménez López, Manuel; Sobrado Calvo, Paloma; Nieto López, Leticia; Cánovas Martínez, Isabel; Salinas Navarro, Manuel; Vidal Sanz, Manuel; Agudo, Marta; Anatomía Humana y PsicobiologíaPurpose. To characterize Brn3a expression in adult albino rat retinal ganglion cells (RGCs) in naïve animals and in animals subjected to complete intraorbital optic nerve transection (IONT) or crush (IONC). methods. Rats were divided into three groups, naïve, IONT, and IONC. Two-, 5-, 9-, or 14-day postlesion (dpl) retinas were examined for immunoreactivity for Brn3a. Before the injury, the RGCs were labeled with Fluorogold (FG; Fluorochrome, Corp. Denver, CO). Brn3a retinal expression was also determined by Western blot analysis. The proportion of RGCs double labeled with Brn3a and FG was determined in radial sections. The temporal course of reduction in Brn3a+ RGCs and FG+ RGCs induced by IONC or IONT was assessed by quantifying, in the same wholemounts, the number of surviving FG-labeled RGCs and Brn3a+RGCs at the mentioned time points. The total number of FG+RGCs was automatically counted in naïve and injured retinas (2 and 5 dpl) or estimated by manual quantification in retinas processed at 9 and 14 dpl. All Brn3a immunopositive RGCs were counted using an automatic routine specifically developed for this purpose. This protocol allowed, as well, the investigation of the spatial distribution of these neurons. results. Brn3a+ cells were only present in the ganglion cell layer and showed a spatial distribution comparable to that of FG+ cells. In the naïve retinal wholemounts the mean (mean ± SEM; n = 14) total number of FG+RGCs and Brn3a+RGCs was 80,251 ± 2,210 and 83,449 ± 4,541, respectively. Whereas in the radial sections, 92.2% of the FG+RGCs were also Brn3a+, 4.4% of the RGCs were Brn3a+FG− and 3.4% were FG+Brn3a−. Brn3a expression pattern was maintained in injured RGCs. The temporal course of Brn3a+RGC and FG+RGC loss induced by IONC or IONT followed a similar trend, but Brn3a+RGCs loss was detected earlier than that of FG+RGCs. Independent of the marker used to detect the RGCs, it was observed that their loss was quicker and more severe after IONT than after IONC. conclusions. Brn3a can be used as a reliable, efficient ex vivo marker to identify and quantify RGCs in control and optic nerve–injured retinas.
- PublicationOpen AccessCardiac Noradrenaline Turnover and Heat Shock Protein 27 Phosphorylation in Dyskinetic Monkeys.(Wiley Online Library, 2019-11) Almela, Pilar; Cuenca Bermejo, Lorena; Yuste, José E.; Estrada, Cristina; Pablos, Vicente de; Bautista Hernández, Víctor; Fernández Villalba, Emiliano; Laorden, María Luisa; Herrero Ezquerro, María Trinidad; Anatomía Humana y PsicobiologíaABSTRACT: Background: Autonomic dysfunction is a well-known dominant symptom in the advanced stages of Parkinson’s disease. However, the role of cardiac sympathetic nerves still needs to be elucidated. Objectives: To evaluate cardiac sympathetic response in Parkinsonian and dyskinetic monkeys. Methods: Adult male monkeys were divided into 1 of the following 3 groups: controls, 1-methyl-4-phenyl-1,2, 3,6-tetrahydropyridine–treated monkeys, and 1-methyl4-phenyl-1,2,3,6-tetrahydropyridine+levodopa–treated animals. Noradrenaline, its metabolite normetanephrine, and phospho-Heat shock proten 27 (p-Hsp27) at erine 82 levels were analyzed in the left and right ventricles of the heart. Tyrosine hydroxylase immunohistochemistry was performed in the ventral mesencephalon. Results: The results were the following: (1) 1-methyl4-phenyl-1,2,3,6-tetrahydropyridine intoxication significantly increased normetanephrine levels and decreased noradrenaline turnover in the right ventricle without changes in the left ventricle; however, (2) levodopa treatment decreased noradrenaline levels and enhanced the normetanephrine/noradrenaline ratio in parallel with a very significant increase of Hsp27 activity in both ventricles. Conclusions: Levodopa treatment could induce protective cardiac effects through the increased Hsp27 activity. © 2019 International Parkinson and Movement Disorder Society
- PublicationEmbargoCircadian phase asessment by ambulatory monitoring in humans: correlation with dim light melatonin onset(Taylor and Francis Group, 2013-10-28) Bonmati-Carrión, María Ángeles; Middleton, Benita; Revell, Victoria L.; Skene, Debra J.; Rol, Maria-Angeles; Madrid, Juan Antonio; Anatomía Humana y PsicobiologíaThe increased prevalence of circadian disruptions due to abnormal coupling between internal and external time makes the detection of circadian phase in humans by ambulatory recordings a compelling need. Here, we propose an accurate practical procedure to estimate circadian phase with the least possible burden for the subject, that is, without the restraints of a constant routine protocol or laboratory techniques such as melatonin quantification, both of which are standard procedures. In this validation study, subjects (N = 13) wore ambulatory monitoring devices, kept daily sleep diaries and went about their daily routine for 10 days. The devices measured skin temperature at wrist level (WT), motor activity and body position on the arm, and light exposure by means of a sensor placed on the chest. Dim light melatonin onset (DLMO) was used to compare and evaluate the accuracy of the ambulatory variables in assessing circadian phase. An evening increase in WT: WTOnset (WTOn) and “WT increase onset” (WTiO) was found to anticipate the evening increase in melatonin, while decreases in motor activity (Activity Offset or AcOff), body position (Position Offset (POff)), integrative TAP (a combination of WT, activity and body position) (TAPOffset or TAPOff) and an increase in declared sleep propensity were phase delayed with respect to DLMO. The phase markers obtained from subjective sleep (R = 0.811), WT (R = 0.756) and the composite variable TAP (R = 0.720) were highly and significantly correlated with DLMO. The findings strongly support a new method to calculate circadian phase based on WT (WTiO) that accurately predicts and shows a temporal association with DLMO. WTiO is especially recommended due to its simplicity and applicability to clinical use under conditions where knowing endogenous circadian phase is important, such as in cancer chronotherapy and light therapy.
- PublicationEmbargoCircadian system functionality, hippocampal oxidative stress, and spatial memory in the APPswe/PS1dE9 transgenic model of Alzheimer disease: effects of melatonin or ramelteon(Taylor and Francis Group, Taylor and Francis, 2012-07-23) Baño-Otalora, Beatriz; Popovic, Natalija; Gambini, Juan; Popovic, Miroljub; Viña, José; Bonet-Costa, Vicent; Reiter, Russel J.; Camello, Pedro Javier; Rol, María Ángeles; Madrid, Juan Antonio; Anatomía Humana y PsicobiologíaAlzheimer disease (AD) is a neurodegenerative disorder that primarily causes β-amyloid accumulation in the brain, resulting in cognitive and behavioral deficits. AD patients, however, also suffer from severe circadian rhythm disruptions, and the underlying causes are still not fully known. Patients with AD show reduced systemic melatonin levels. This may contribute to their symptoms, since melatonin is an effective chronobiotic and antioxidant with neuroprotective properties. Here, the authors critically assessed the effects of long-term melatonin treatment on circadian system function, hippocampal oxidative stress, and spatial memory performance in the APPswe/PS1 double transgenic (Tg) mouse model of AD. To test if melatonin MT1/MT2 receptor activation, alone, was involved, the authors chronically treated some mice with the selective MT1/MT2 receptor agonist ramelteon. The results indicate that many of the circadian and behavioral parameters measured, including oxidative stress markers, were not significantly affected in these AD mice. During the day, though, Tg controls (Tg-CON) showed significantly higher mean activity and body temperature (BT) than wild-type (WT) mice. Overall, BT rhythm amplitude was significantly lower in Tg than in WT mice. Although melatonin treatment had no effect, ramelteon significantly reduced the amplitude of the BT rhythm in Tg mice. Towards the end of the experiment, Tg mice treated with ramelteon (Tg-RAM) showed significantly higher circadian rhythm fragmentation than Tg-CON and reduced circadian BT rhythm strength. The free-running period (τ) for the BT and locomotor activity (LA) rhythms of Tg-CON was <24 h. Whereas melatonin maintained τ at 24 h for BT and LA in both genotypes, ramelteon treatment had no effect. In the behavioral tests, the number of approaches and time spent exploring novel objects were significantly higher in Tg-CON than WT controls. Brain tissue analysis revealed significant reduction in hippocampal protein oxidation in Tg-MEL and Tg-RAM compared with Tg-CON animals. These results suggest that not all aspects of the circadian system are affected in the APPswe/PS1 mice. Therefore, care should be taken when extending the results obtained in Tg mice to develop new therapies in humans. This study also revealed the complexity in the therapeutic actions of melatonin and ramelteon in this mouse model of AD.
- PublicationOpen AccessCognitive Impairment After Sleep Deprivation Rescued by Transcranial Magnetic Stimulation Application in Octodon degus(2015) Estrada Esteban, C.; Fernández Gómez, F. J.; López López, D.; González Cuello, Ana María; Toledo Romero, Francisco; Fernández Villalba, Emiliano; Herrero Ezquerro, María Trinidad; Anatomía Humana y Psicobiología
- PublicationOpen AccessCorrelated color temperature and light intensity: Complementary features in nonvisual light field(Public Library of Science, 2021-07-12) Arguelles-Prieto, Raquel; Madrid, Juan Antonio; Rol, Maria-Angeles; Bonmatí-Carrión, María Ángeles; Anatomía Humana y PsicobiologíaAn appropriate exposure to the light-dark cycle, with high irradiances during the day and darkness during the night is essential to keep our physiology on time. However, considering the increasing exposure to artificial light at night and its potential harmful effects on health (i.e. chronodisruption and associated health conditions), it is essential to understand the non-visual effects of light in humans. Melatonin suppression is considered the gold standard for nocturnal light effects, and the activation of intrinsically photosensitive retinal ganglion cells (ipRGCs) through the assessment of pupillary light reflex (PLR) has been recently gaining attention. Also, some theoretical models for melatonin suppression and retinal photoreceptors activation have been proposed. Our aim in this study was to determine the influence of correlated color temperature (CCT) on melatonin suppression and PLR, considering two commercial light sources, as well as to explore the possible correlation between both processes. Also, the contribution of irradiance (associated to CCT) was explored through mathematical modelling on a wider range of light sources. For that, melatonin suppression and PLR were experimentally assessed on 16 healthy and young volunteers under two light conditions (warmer, CCT 3000 K; and cooler, CCT 5700 K, at ~5·1018 photons/cm2/sec). Our experimental results yielded greater post-stimulus constriction under the cooler (5700 K, 13.3 ± 1.9%) than under the warmer light (3000 K, 8.7 ± 1.2%) (p < 0.01), although no significant differences were found between both conditions in terms of melatonin suppression. Interestingly, we failed to demonstrate correlation between PLR and melatonin suppression. Although methodological limitations cannot be discarded, this could be due to the existence of different subpopulations of Type 1 ipRGCs differentially contributing to PLR and melatonin suppression, which opens the way for further research on ipRGCs projection in humans. The application of theoretical modelling suggested that CCT should not be considered separately from irradiance when designing nocturnal/diurnal illumination systems. Further experimental studies on wider ranges of CCTs and light intensities are needed to confirm these conclusions.
- PublicationOpen AccessData base: Estudio satisfacción. Uso de gamificación en docencia de Anatomía humana (encuestas)López González, Laura; Anatomía Humana y Psicobiología; Facultad de Medicina
- PublicationOpen AccessDe novo mutations in PLXND1 and REV3L cause Mobius syndrome(2015-06-12) Tomas-Roca, Laura; Tsaalbi-Shtylik, Anastasia; Jansen, Jacob G.; Singh, Manvendra K.; Epstein, Jonathan A.; Altunoglu, Umut; Verzijl, Harriette; Soria, Laura; Beusekom, Ellen van; Roscioli, Tony; Iqbal, Zafar; Gilissen, Christian; Hoischen, Alexander; de Brouwer, Arjan P.M.; Erasmus, Corrie; Schubert, Dirk; Brunner, Han; Perez Aytes, Antonio; Marin, Faustino; Aroca Tejedor, Pilar; Kayserili, Hulya; Carta, Arturo; de Wind, Niels; Padberg, George W.; Bokhoven, Hans van; Anatomía Humana y Psicobiología; Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, PO Box 9101, Nijmegen 6500 HB,The Netherlands.; Department of Human Genetics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.; Department of Cell andDevelopmental Biology, Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, 9-105 SCTR, 3400 Civic Center Boulevard,Philadelphia, Pennsylvania 19104, USA; Signature Research Program in Cardiovascular and Metabolic Disorders, Duke-NUS Graduate Medical SchoolSingapore, National Heart Center Singapore, 8 College Road, Singapore 169857, Singapore; Medical Genetics Department, Istanbul Medical Faculty,Istanbul University, Millet Caddesi, Capa, Fatih 34093, Turkey.; Department of Neurology, Radboud University Medical Center, Donders Institute for Brain,Cognition and Behaviour, PO Box 9101, Nijmegen 6500 HB, The Netherlands.; The Kinghorn Centre for Clinical Genomics, Garvan Institute of MedicalResearch, Sydney, New South Wales 2010, Australia; Department of Human Genetics, Radboud University Medical Center, Radboud Institute for MolecularLife Sciences (RIMLS), PO Box 9101, Nijmegen 6500 HB, The Netherlands.; Department of Cognitive Neuroscience, Radboud University Medical Center,Donders Institute for Brain, Cognition and Behaviour, PO Box 9101, Nijmegen 6500 HB, The Netherlands; Department of Clinical Genetics, MaastrichtUniversity Medical Center, PO Box 5800, Maastricht 6200AZ, The Netherlands.; Dysmorphology and Reproductive Genetics Unit, Moebius SyndromeFoundation of Spain, University Hospital LA FE, Valencia 46540, Spain.; Ophthalmology Unit, Department of Biomedical, Biotechnological and TranslationalSciences (S.Bi.Bi.T.), University of Parma, via Gramsci 14, 43126, Parma, ItalyMo ̈bius syndrome (MBS) is a neurological disorder that is characterized by paralysis of thefacial nerves and variable other congenital anomalies. The aetiology of this syndrome hasbeen enigmatic since the initial descriptions by von Graefe in 1880 and by Mo ̈bius in 1888,and it has been debated for decades whether MBS has a genetic or a non-genetic aetiology.Here, we reportde novomutations affecting two genes,PLXND1andREV3Lin MBS patients.PLXND1 and REV3L represent totally unrelated pathways involved in hindbrain development:neural migration and DNA translesion synthesis, essential for the replication of endogenouslydamaged DNA, respectively. Interestingly, analysis ofPlxnd1andRev3lmutant mice showsthat disruption of these separate pathways converge at the facial branchiomotor nucleus,affecting either motoneuron migration or proliferation. The finding thatPLXND1andREV3Lmutations are responsible for a proportion of MBS patients suggests thatde novomutations inother genes might account for other MBS patients
- PublicationRestrictedDistinct Regulation of Dopamine D3 Receptor in the Basolateral Amygdala and Dentate Gyrus during the Reinstatement of Cocaine CPP Induced by Drug Priming and Social Stress(MDPI, 2021-03-18) Guerrero-Bautista, Rocío; Franco-García, Aurelio; Hidalgo, Juana M.; Fernández-Gómez, Francisco José; Ribeiro Do Couto, Bruno; Milanés, M. Victoria; Núñez, Cristina; Farmacología; Anatomía Humana y Psicobiología