Mild malformation of cortical development with oligodendroglial hyperplasia in frontal lobe epilepsy (MOGHE): a report of the first case in Bulgaria.

Herein, we report the first case of mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE) in Bulgaria. It is a newly recognised clinico-pathological entity with medically intractable focal epilepsy in paediatric patients. The patient of interest is a 9-year-old boy who has been suffering from refractory epilepsy since the age of three. Positron emission tomography revealed a consistent hypometabolism with maximum in the orbitofrontal and fronto-opercular cortex, as well as in the adjacent anterior insula and the anterior temporal regions. A left frontal corticotomy anterior from the precentral sulcus, left insulectomy and temporal disconnection were performed. Pathomorphological examination of the material from the resected brain tissues demonstrated oligodendroglial hyperplasia with blurring of grey-white-matter boundaries and presence of subcortical heterotopic neurones. Eighteen months post-surgically the patient is seizure-free and drug-free. The observed oligodendroglial hyperplasia with increased proliferative activity and heterotopic neurones in the white matter with blurring of grey-white-matter junctions are the histopathological hallmarks of MOGHE. More new cases are needed to establish further data about this distinct entity in frontal lobe epilepsy.

Role of artificial intelligence, machine learning and deep learning models in corneal disorders - A narrative review.

In the last decade, artificial intelligence (AI) has significantly impacted ophthalmology, particularly in managing corneal diseases, a major reversible cause of blindness. This review explores AI's transformative role in the corneal subspecialty, which has adopted advanced technology for superior clinical judgment, early diagnosis, and personalized therapy. While AI's role in anterior segment diseases is less documented compared to glaucoma and retinal pathologies, this review highlights its integration into corneal diagnostics through imaging techniques like slit-lamp biomicroscopy, anterior segment optical coherence tomography (AS-OCT), and in vivo confocal biomicroscopy. AI has been pivotal in refining decision-making and prognosis for conditions such as keratoconus, infectious keratitis, and dystrophies. Multi-disease deep learning neural networks (MDDNs) have shown diagnostic ability in classifying corneal diseases using AS-OCT images, achieving notable metrics like an AUC of 0.910. AI's progress over two decades has significantly improved the accuracy of diagnosing conditions like keratoconus and microbial keratitis. For instance, AI has achieved a 90.7% accuracy rate in classifying bacterial and fungal keratitis and an AUC of 0.910 in differentiating various corneal diseases. Convolutional neural networks (CNNs) have enhanced the analysis of color-coded corneal maps, yielding up to 99.3% diagnostic accuracy for keratoconus. Deep learning algorithms have also shown robust performance in detecting fungal hyphae on in vivo confocal microscopy, with precise quantification of hyphal density. AI models combining tomography scans and visual acuity have demonstrated up to 97% accuracy in keratoconus staging according to the Amsler-Krumeich classification. However, the review acknowledges the limitations of current AI models, including their reliance on binary classification, which may not capture the complexity of real-world clinical presentations with multiple coexisting disorders. Challenges also include dependency on data quality, diverse imaging protocols, and integrating multimodal images for a generalized AI diagnosis. The need for interpretability in AI models is emphasized to foster trust and applicability in clinical settings. Looking ahead, AI has the potential to unravel the intricate mechanisms behind corneal pathologies, reduce healthcare's carbon footprint, and revolutionize diagnostic and management paradigms. Ethical and regulatory considerations will accompany AI's clinical adoption, marking an era where AI not only assists but augments ophthalmic care.

Herbert Major on the insula: An early depiction of von Economo neurones?

Herbert Major (1850-1921) undertook histopathological studies of human and non-human primate brains at the West Riding Lunatic Asylum in Wakefield, England, during the 1870s. Two of his papers specifically investigated the structure of the island of Reil, or insula, "with the view of ascertaining its exact structure". In addition to describing and illustrating its lamination as six-layered, Major also identified "spindle-shaped" cells in the lower layers of human brains, but not in non-human primates. His written description, including measurements of cell body size, and illustration are suggestive that these were the neurones later described in the frontoinsular and anterior cingulate cortex by Constantin von Economo and Georg N. Koskinas and which were subsequently given the eponym "von Economo neurones". von Economo noted that this special neuronal type had been previously seen by Betz (1881), Hammarberg (1895), and Ramón y Cajal (1899-1904), but he did not mention Major's works. Major also ascribed linguistic functions to the insula. Hence, with respect to both anatomical and physiological features, Major may have pre-empted the findings of later research on this structure.

Activation of glutamatergic neurones in the pedunculopontine tegmental nucleus promotes cortical activation and behavioural emergence from sevoflurane-induced unconsciousness in mice.

BACKGROUND: The neural mechanisms underlying sevoflurane-induced loss of consciousness and recovery of consciousness after anaesthesia remain unknown. We investigated whether glutamatergic pedunculopontine tegmental nucleus (PPT) neurones are involved in the regulation of states of consciousness under sevoflurane anaesthesia. METHODS: In vivo fibre photometry combined with electroencephalography (EEG)/electromyography recording was used to record changes in the activity of glutamatergic PPT neurones under sevoflurane anaesthesia. Chemogenetic and cortical EEG recordings were used to explore their roles in the induction of and emergence from sevoflurane anaesthesia. Optogenetic methods combined with EEG recordings were used to explore the roles of glutamatergic PPT neurones and of the PPT-ventral tegmental area pathway in maintenance of anaesthesia. RESULTS: The population activity of glutamatergic PPT neurones was reduced before sevoflurane-induced loss of righting reflex and gradually recovered after return of righting reflex. Chemogenetic inhibition of glutamatergic PPT neurones accelerated induction of anaesthesia (hM4Di-CNO vs mCherry-CNO, 76 [17] vs 121 [27] s, P<0.0001) and delayed emergence from sevoflurane anaesthesia (278 [98] vs 145 [53] s, P<0.0001) but increased sevoflurane sensitivity. Optogenetic stimulation of glutamatergic PPT neurons or of the PPT-ventral tegmental area pathway promoted cortical activation and behavioural emergence during steady-state sevoflurane anaesthesia, reduced the depth of anaesthesia, and caused cortical arousal during sevoflurane-induced EEG burst suppression. CONCLUSIONS: Glutamatergic PPT neurones regulate induction and emergence of sevoflurane anaesthesia.

[François Gros' laboratory at the Collège de France]. / Le laboratoire de François Gros au Collège de France.

I was recruited by François Gros as a PhD student in his laboratory at the Institut de Biologie Physico-Chimique in 1965, and continued to work with him after I graduated. In 1973, when he was appointed Professor of Cellular Biochemistry at the Collège de France, François decided to set up a team working on neuronal differentiation. He asked me to take part in this new scientific adventure. Here I'd like to talk about the members of his laboratory and some of their scientific work, in particular that on the cytoskeleton of neurons.

J'ai été recrutée par François Gros comme étudiante dans son laboratoire à l'Institut de Biologie Physico-Chimique en 1965 et j'ai continué à travailler avec lui après ma thèse. En 1973, quand il a été nommé professeur titulaire de la chaire de Biochimie cellulaire au Collège de France, François a décidé d'y créer une équipe travaillant sur la différenciation des cellules nerveuses. Il m'a demandé de participer à cette nouvelle aventure scientifique. J'évoque ici les membres de son laboratoire ainsi que certains de leurs travaux scientifiques, notamment ceux concernant le cytosquelette des neurones.

Gastrointestinal syndromes preceding a diagnosis of Parkinson's disease: testing Braak's hypothesis using a nationwide database for comparison with Alzheimer's disease and cerebrovascular diseases.

OBJECTIVE: Braak's hypothesis states that Parkinson's disease (PD) originates in the gastrointestinal (GI) tract, and similar associations have been established for Alzheimer's disease (AD) and cerebrovascular diseases (CVD). We aimed to determine the incidence of GI syndromes and interventions preceding PD compared with negative controls (NCs), AD and CVD. DESIGN: We performed a combined case-control and cohort study using TriNetX, a US based nationwide medical record network. Firstly, we compared subjects with new onset idiopathic PD with matched NCs and patients with contemporary diagnoses of AD and CVD, to investigate preceding GI syndromes, appendectomy and vagotomy. Secondly, we compared cohorts with these exposures to matched NCs for the development of PD, AD and CVD within 5 years. RESULTS: We identified 24 624 PD patients in the case-control analysis and matched 18 cohorts with each exposure to their NCs. Gastroparesis, dysphagia, irritable bowel syndrome (IBS) without diarrhoea and constipation showed specific associations with PD (vs NCs, AD and CVD) in both the case-control (odds ratios (ORs) vs NCs 4.64, 3.58, 3.53 and 3.32, respectively, all p<0.0001) and cohort analyses (relative risks (RRs) vs NCs 2.43, 2.27, 1.17 and 2.38, respectively, all p<0.05). While functional dyspepsia, IBS with diarrhoea, diarrhoea and faecal incontinence were not PD specific, IBS with constipation and intestinal pseudo-obstruction showed PD specificity in the case-control (OR 4.11) and cohort analysis (RR 1.84), respectively. Appendectomy decreased the risk of PD in the cohort analysis (RR 0.48). Neither inflammatory bowel disease nor vagotomy were associated with PD. CONCLUSION: Dysphagia, gastroparesis, IBS without diarrhoea and constipation might specifically predict Parkinson's disease.

Translational and Posttranslational Dynamics in a Model Peptidergic System.

The cell bodies of hypothalamic magnocellular neurones are densely packed in the hypothalamic supraoptic nucleus, whereas their axons project to the anatomically discrete posterior pituitary gland. We have taken advantage of this unique anatomical structure to establish proteome and phosphoproteome dynamics in neuronal cell bodies and axonal terminals in response to physiological stimulation. We have found that proteome and phosphoproteome responses to neuronal stimulation are very different between somatic and axonal neuronal compartments, indicating the need of each cell domain to differentially adapt. In particular, changes in the phosphoproteome in the cell body are involved in the reorganization of the cytoskeleton and in axonal terminals the regulation of synaptic and secretory processes. We have identified that prohormone precursors including vasopressin and oxytocin are phosphorylated in axonal terminals and are hyperphosphorylated following stimulation. By multiomic integration of transcriptome and proteomic data, we identify changes to proteins present in afferent inputs to this nucleus.

Imaging the Hypothalamo-Neurohypophysial System.

The hypothalamo-neurohypophysial system (HNS) is a brain peptidergic neurosecretory apparatus which is composed of arginine vasopressin (AVP) and oxytocin (OXT) magnocellular neurones and their neuronal processes in the posterior pituitary (PP). In response to specific stimuli, AVP and OXT are secreted into the systemic circulation at the neurovascular interface of the PP, where they act as hormones, but they can also behave as neurotransmitters when released at the somatodendritic compartment or by axon collaterals to other brain regions. Because these peptides are crucial for several physiological processes, including fluid homoeostasis and reproduction, it is of great importance to map the HNS connectome in its entirety in order to understand its functions. In recent years, advances in imaging technologies have provided considerable new information about the HNS. These approaches include the use of reporter proteins under the control of specific promoters, viral tracers, brain-clearing methods, genetically encoded indicators, sniffer cells, mass spectrometry imaging, and spatially resolved transcriptomics. In this review, we illustrate how these latest approaches have enhanced our understanding of the structure and function of the HNS and how they might contribute further in the coming years.

Peripheral nerves in the tibial subchondral bone : the role of pain and homeostasis in osteoarthritis.

Osteoarthritis (OA) is a highly prevalent degenerative joint disorder characterized by joint pain and physical disability. Aberrant subchondral bone induces pathological changes and is a major source of pain in OA. In the subchondral bone, which is highly innervated, nerves have dual roles in pain sensation and bone homeostasis regulation. The interaction between peripheral nerves and target cells in the subchondral bone, and the interplay between the sensory and sympathetic nervous systems, allow peripheral nerves to regulate subchondral bone homeostasis. Alterations in peripheral innervation and local transmitters are closely related to changes in nociception and subchondral bone homeostasis, and affect the progression of OA. Recent literature has substantially expanded our understanding of the physiological and pathological distribution and function of specific subtypes of neurones in bone. This review summarizes the types and distribution of nerves detected in the tibial subchondral bone, their cellular and molecular interactions with bone cells that regulate subchondral bone homeostasis, and their role in OA pain. A comprehensive understanding and further investigation of the functions of peripheral innervation in the subchondral bone will help to develop novel therapeutic approaches to effectively prevent OA, and alleviate OA pain. Cite this article: Bone Joint Res 2022;11(7):439-452.

Pharmacological evidence that GABA-induced relaxation of rat proximal duodenum longitudinal muscle depends on NKCC cotransporter activity and Ca2+ influx.

γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter in adult central nervous system (CNS) synapses, but it excites immature CNS neurons as well as neurons in the myenteric plexus. The present work aimed to determine whether GABA-induced nonadrenergic, noncholinergic (NANC) neuronal-mediated relaxation of the rat duodenum is dependent on the activity of Na+ K+ Cl- cotransporters (NKCC) and requires calcium influx. In the presence of guanethidine (3 µmol/L), atropine (3 µmol/L), and indomethacin (1 µmol/L), relaxations induced by GABA (100 µmol/L), KCl (5-10 mmol/L) and electrical field stimulation (1-8 Hz, 2 ms, 60 V), but not those induced by bradykinin (10-100 nmol/L) were abolished by lidocaine (300 µmol/L). However, only GABA-induced relaxations were reduced in a concentration-dependent manner by the NKCC1/2 inhibitors bumetanide (0.1-1 µmol/L) and furosemide (1-10 µmol/L). GABA-induced NANC neuronal relaxation was abolished by bicuculline (30 µmol/L) and inhibited by N-nitroarginine methyl ester (l-NAME, 300 µmol/L). The ω-conotoxin GVIA (1 µmol/L), which acts exclusively on neuronal CaV2 channels, but not on smooth muscle voltage-gated Ca2+ CaV1 channels, and nonselective blockers of these channels (verapamil 100 nmol/L and ruthenium red 10 µmol/L), reduced GABA-induced relaxations. These results showed that the activation of GABAA receptors induces NANC nitrergic neuronal relaxations in the rat duodenum, which depend on NKCC activity and CaV2 channel activation, suggesting that this phenomenon results from neuronal depolarization promoted by Cl- efflux through GABAA receptors, with subsequent Ca2+ influx and nitric oxide release.

Peripheral chemoreflex activation induces expiratory but not inspiratory excitation of C1 pre-sympathetic neurones of rats.

AIMS: Stimulation of peripheral chemoreceptors, as during hypoxia, increases breathing and respiratory-related sympathetic bursting. Activation of catecholaminergic C1 neurones induces sympathoexcitation, while its ablation reduces the chemoreflex sympathoexcitatory response. However, no study has determined the respiratory phase(s) in which the pre-sympathetic C1 neurones are recruited by peripheral chemoreceptor and whether C1 neurone activation affects all phases of respiratory modulation of sympathetic activity. We addressed these unknowns by testing the hypothesis that peripheral chemoreceptor activation excites pre-sympathetic C1 neurones during inspiration and expiration. METHODS: Using the in situ preparation of rat, we made intracellular recordings from baroreceptive pre-sympathetic C1 neurones during peripheral chemoreflex stimulation. We optogenetically activated C1 neurones selectively and compared any respiratory-phase-related increases in sympathetic activity with that which occurs following stimulation of the peripheral chemoreflex. RESULTS: Activation of peripheral chemoreceptors using cytotoxic hypoxia (potassium cyanide) increased the firing frequency of C1 neurones and both the frequency and amplitude of their excitatory post-synaptic currents during the phase of expiration only. In contrast, optogenetic stimulation of C1 neurones activates inspiratory neurones, which secondarily inhibit expiratory neurones, but produced comparable increases in sympathetic activity across all phases of respiration. CONCLUSION: Our data reveal that the peripheral chemoreceptor-mediated expiratory-related sympathoexcitation is mediated through excitation of expiratory neurones antecedent to C1 pre-sympathetic neurones; these may be found in the Kölliker-Fuse nucleus. Despite peripheral chemoreceptor excitation of inspiratory neurones, these do not trigger C1 neurone-mediated increases in sympathetic activity. These studies provide compelling novel insights into the functional organization of respiratory-sympathetic neural networks.

The past, present, and future of traumatic spinal cord injury therapies: a review.

This review provides a concise outline of the advances made in the care of patients and to the quality of life after a traumatic spinal cord injury (SCI) over the last century. Despite these improvements reversal of the neurological injury is not yet possible. Instead, current treatment is limited to providing symptomatic relief, avoiding secondary insults and preventing additional sequelae. However, with an ever-advancing technology and deeper understanding of the damaged spinal cord, this appears increasingly conceivable. A brief synopsis of the most prominent challenges facing both clinicians and research scientists in developing functional treatments for a progressively complex injury are presented. Moreover, the multiple mechanisms by which damage propagates many months after the original injury requires a multifaceted approach to ameliorate the human spinal cord. We discuss potential methods to protect the spinal cord from damage, and to manipulate the inherent inhibition of the spinal cord to regeneration and repair. Although acute and chronic SCI share common final pathways resulting in cell death and neurological deficits, the underlying putative mechanisms of chronic SCI and the treatments are not covered in this review.

Desempeño sociocomunicativo en niños con TEA. Un análisis desde la Lógica Transcursiva / Acompliment social i comunicatiu en nens amb TEA. Una anàlisi des de la Lògica Transcursiva / Socio-communicative performance in children with ASD. An analysis from Transcursive Logic

El propósito de este trabajo es revisar los fundamentos neurobiológicos y psíquicos de la llamada Teoría de la Mente (ToM), cuyas supuestas fallas en su desarrollo pretenden explicar la aparición de los trastornos sociocomunicativos que presentan las personas con Trastorno del Espectro Autista (TEA) para arrojar algo de luz sobre la aparición de algunos signos como, por ejemplo, los rasgos no sociales del autismo. A partir de un análisis crítico de algunos aportes de las Ciencias Cognitivas, llegamos a la conclusión de que la Teoría de la Mente es un modelo inapropiado para evaluar la comprensión del lenguaje, porque no tiene en cuenta sus aspectos subjetivos. La Lógica Transcursiva, como contrapartida, aporta una interpretación del proceso comunicativo y de esa forma, demuestra la improcedencia de la Teoría de la Mente.(AU)

The purpose of this paper is to review the neurobiological and psychological foundations of the so-called Theory of Mind (ToM), whose alleged flaws in its development pretend to explain the appearance of the socio-communicative disorders presented by people with Autism Spectrum Disorder (ASD) in order to shed some light on the appearance of some signs such as, for example, the non-social features of autism. From a critical analysis of some contributions from the Cognitive Sciences, we conclude that the Theory of Mind is an inappropriate model to assess language comprehension because it does not take into account its subjective aspects. Transcursive Logic, on the other hand, provides an interpretation of the communicative process and thus demonstrates the inappropriateness of the Theory of Mind.(AU)

El propòsit d'aquest treball és revisar els fonaments neurobiològics i psíquics de l'anomenada Teoria de la Ment (ToM), en la que les suposades falles en el seu desenvolupament pretenen explicar l'aparició dels trastorns socials i comunicatius que presenten les persones amb Trastorn de l'espectre autista (TEA) per clarificar l'aparició d'alguns signes com, per exemple, els trets no socials de l'autisme. A partir d'una anàlisi crítica d'alguns aportacions de les Ciències Cognitives, arribem a la conclusió que la ToM és un model inadequat per avaluar la comprensió de llenguatge, perquè no té en compte els seus aspectes subjectius. La Lògica Transcursiva, com a contrapartida, aporta una interpretació del procés comunicatiu i, d'aquesta forma, demostra la improcedència de la ToM.(AU)

Order of importance of anatomical risk factors in Kienböck's disease: An artificial neural network study.

Anatomical variations in bony structures around the wrist have been considered as risk factors for Kienböck's disease: ulnar variance, Nattrass index, ulnar variance/capitate height ratio and presence of a lunohamate joint. This study aimed to assess the order of importance of these variations as risk factors for Kienböck's disease. Two groups were formed: patients (n = 58) and controls (n = 235). On posteroanterior radiographs in the two groups, these risk factors were examined by four raters. After inter-rater correlation analysis, an artificial neural network was used to estimate their relative importance. All parameters showed statistically significant inter-rater correlation (p < 0.05). The artificial neural network study showed that the three most important risk factors, in descending order, were: Nattrass index, ulnar variance/capitate height ratio and negative ulnar variance. The study determined the order of importance of the anatomical risk factors for Kienböck's disease measurable on posteroanterior wrist radiographs. Although these findings seem to be useful in the diagnostic algorithm of Kienböck's disease, multivariate analysis of all measurable risk factors is still needed. The artificial neural network approach could contribute to such a comprehensive study.

Aß-Induced Alterations in Membrane Lipids Occur before Synaptic Loss Appears.

Loss of active synapses and alterations in membrane lipids are crucial events in physiological aging as well as in neurodegenerative disorders. Both are related to the abnormal aggregation of amyloid-beta (Aß) species, generally known as amyloidosis. There are two major known human Aß species: Aß(1-40) and Aß(1-42). However, which of these species have more influence on active synapses and membrane lipids is still poorly understood. Additionally, the time-dependent effect of Aß species on alterations in membrane lipids of hippocampal neurones and glial cells remains unknown. Therefore, our study contributes to a better understanding of the role of Aß species in the loss of active synapses and the dysregulation of membrane lipids in vitro. We showed that Aß(1-40) or Aß(1-42) treatment influences membrane lipids before synaptic loss appears and that the loss of active synapses is not dependent on the Aß species. Our lipidomic data analysis showed early changes in specific lipid classes such as sphingolipid and glycerophospholipid neurones. Our results underscore the potential role of lipids as a possible early diagnostic biomarker in amyloidosis-related disorders.

[Mirror neurons, neural substrate of action understanding?] / Neurones miroirs, substrat neuronal de la compréhension de l'action?

In 1992, the Laboratory of Human Physiology at the University of Parma (Italy) publish a study describing "mirror" neurons in the macaque that activate both when the monkey performs an action and when it observes an experimenter performing the same action. The research team behind this discovery postulates that the mirror neurons system is the neural basis of our ability to understand the actions of others, through the motor mapping of the observed action on the observer's motor repertory (direct-matching hypothesis). Nevertheless, this conception met serious criticism. These critics attempt to relativize their function by placing them within a network of neurocognitive and sensory interdependencies. In short, the essential characteristic of these neurons is to combine the processing of sensory information, especially visual, with that of motor information. Their elementary function would be to provide a motor simulation of the observed action, based on visual information from it. They can contribute, with other non-mirror areas, to the identification/prediction of the action goal and to the interpretation of the intention of the actor performing it. Studying the connectivity and high frequency synchronizations of the different brain areas involved in action observation would likely provide important information about the dynamic contribution of mirror neurons to "action understanding". The aim of this review is to provide an up-to-date analysis of the scientific evidence related to mirror neurons and their elementary functions, as well as to shed light on the contribution of these neurons to our ability to interpret and understand others' actions.

Desempeño sociocomunicativo en niños con TEA. Un análisis desde la Lógica Transcursiva / Acompliment social i comunicatiu en nens amb TEA. Una anàlisi des de la Lògica Transcursiva / Socio-communicative performance in children with ASD. An analysis from Transcursive Logic

El propósito deeste trabajo es revisar los fundamentos neurobiológicos y psíquicos de la llamada Teoría de la Mente (ToM),cuyas supuestas fallas en su desarrollo pretenden explicar la aparición de los trastornos sociocomunicativos quepresentan las personas con Trastorno del Espectro Autista (TEA) para arrojar algo de luz sobre la aparición dealgunos signos como, por ejemplo, los rasgos no sociales del autismo. A partir de un análisis crítico de algunosaportes de las Ciencias Cognitivas, llegamos a la conclusión de que la ToM es un modelo inapropiado para eva-luar la comprensión del lenguaje, porque no tiene en cuenta sus aspectos subjetivos. La Lógica Transcursiva,como contrapartida, aporta una interpretación del proceso comunicativo y, de esa forma, demuestra la improcedencia de la ToM.(AU)

The purpose ofthis paper is to review the neurobiological and psychological foundations of the so-called Theory of Mind (ToM),whose alleged flaws in its development pretend to explain the appearance of the socio-communicative disor-ders presented by people with Autism Spectrum Disorder (ASD) in order to shed some light on the appearanceof some signs such as, for example, the non-social features of autism. From a critical analysis of some contri-butions from the Cognitive Sciences, we conclude that the Theory of Mind is an inappropriate model to assesslanguage comprehension because it does not take into account its subjective aspects. Transcursive Logic, onthe other hand, provides an interpretation of the communicative process and thus demonstrates the inappropriateness of the Theory of Mind.(AU)

El propòsitd’aquest treball és revisar els fonaments neurobiològics i psíquics de l’anomenada Teoria de la Ment (ToM), en laque les suposades falles en el seu desenvolupament pretenen explicar l’aparició dels trastorns socials i comunica-tius que presenten les persones amb trastorn de l’espectre autista (TEA) per clarificar l’aparició d’alguns signescom, per exemple, els trets no socials de l’autisme. A partir d’una anàlisi crítica d’alguns aportacions de les Cièn-cies Cognitives, arribem a la conclusió que la ToM és un model inadequat per avaluar la comprensió de llenguatge,perquè no té en compte els seus aspectes subjectius. La Lògica Transcursiva, com a contrapartida, aporta unainterpretació del procés comunicatiu i, d’aquesta forma, demostra la improcedència de la ToM.(AU)

Roles of fibroblast growth factor 21 in the control of depression-like behaviours after social defeat stress in male rodents.

Fibroblast growth factor 21 (FGF21) modulates energy metabolism and neuroendocrine stress responses. FGF21 synthesis is increased after environmental or metabolic challenges. Detailed roles of FGF21 in the control of behavioural disturbances under stressful conditions remain to be clarified. Here, we examined the roles of FGF21 in the control of behavioural changes after social defeat stress in male rodents. Central administration of FGF21 increased the number of tyrosine hydroxylase-positive catecholaminergic cells expressing c-Fos protein, an activity marker of neurones, in the nucleus tractus solitarius and area postrema. Double in situ hybridisation showed that some catecholaminergic neurones in the dorsal medulla oblongata expressed ß-Klotho, an essential co-receptor for FGF21, in male mice. Social defeat stress increased FGF21 concentrations in the plasma of male mice. FGF21-deficient male mice showed social avoidance in a social avoidance test with C57BL/6J mice (background strain of FGF21-deficient mice) and augmented immobility behaviour in a forced swimming test after social defeat stress. On the other hand, overexpression of FGF21 by adeno-associated virus vectors did not significantly change behaviours either in wild-type male mice or FGF21-deficient male mice. The present data are consistent with the view that endogenous FGF21, possibly during the developmental period, has an inhibitory action on stress-induced depression-like behaviour in male rodents.