Academic literature on the topic 'Settore BIO/16 - Anatomia Umana'

Magnetic resonance diffusion-based tractography techniques have offered a real breakthrough in brain studies. These methods allow, for the first time, to explore the anatomical organization of white matter pathways in humans, in-vivo and non-invasively. As any other method, diffusion-based tractography has limitations. The inherent limits related to the indirect measurement of the diffusion signal, and the strong dependence of this technique on acquisition, models and algorithm parameters, prevents the reliable reconstruction of some major white matter bundles. This dissertation targets the methods, limitations, improvements, and validation of tracking methods, with applications in neurobiological and clinical research. In particular, the main work focuses on a white matter bundle that represents a notable omission in tractography studies: the acoustic radiation (AR), a major projection sensory pathway conveying auditory information from the thalamus to the auditory cortex. Topographical knowledge of this bundle is scarce, and its in-vivo tractography reconstruction remains challenging, preventing the investigation of auditory and language functional mechanisms in humans. This dissertation investigates, for the first time, the topography of the AR using post-mortem blunt dissections and provides a detailed description of the trajectory of these fibres and their relationship with major neighbouring white matter bundles. The topographical information is then applied to conduct an investigation on the effects of different MRI acquisition and tractography parameters on the in-vivo tractography reconstruction of the AR. An optimal set of parameters is obtained for AR reconstructions and used to build the first tractography atlas of the acoustic radiation. The AR atlas is then applied to study congenital deaf patients. The optimized reconstruction parameters and the atlas generated in this dissertation may be used in future studies interested in identifying and characterizing the AR. The reliable 3D reconstruction of this bundle will improve our understanding of the functional mechanisms underlying hearing and language in healthy subjects and patients, as well as in neurosurgical applications.

Telemedicine consists in the use of telecommunication technologies to provide healthcare services, overcoming geographic, temporal, social, and cultural barriers. Today telemedicine is a developed field which includes about 50 different subspecialties: neuropsychology is one of them. Allowing the objective evaluation of the cognitive state of individuals, neuropsychology is a discipline of wide application; it also contributes significantly to an early diagnosis of subjects suspected to develop cognitive impairments due to Alzheimer disease or other degenerative dementias. Subjects at risk, and subjects who have already develop the illness, would particularly benefit of a telehealth intervention, which allows to overcome the barriers of space and time, and to provide an evaluation, as well as the therapy monitoring. These aspects would be particularly important for subjects who live far from health institutions , as those of rural areas. Obviously, we need to be sure that the results of the Tele-Neuropsychological assessment are comparable to those obtained via the classic '' face to face '' administration. This is the purpose of this research. We aimed in fact to compare the performances obtained in the two conditions at the MMSE test and the ADAS Cog test. To this purpose, we submitted a group of subjects affected by mild to moderate Alzheimer disease with associated vascular damages, to MMSE and the ADAS COG test, and performed a statistical analysis of data through a two sided Student ''t'' test. We found that the administration modality had no significant impact on the results. In fact, no significant difference was found neither in the MMSE, or in the ADAS_Cog scores administered by telehealth versus ''face to face''. While the results obtained at the MMSE confirm some previous data, this is, at our knowledge, the first study done on the ADAS_Cog, a test. Even if the conditions we employed in this research are not entirely superposable to those of patients staying at home (we evaluated the feasibility of teleheath by locating the patient and his caregiver in another room of the memory clinic ), we are confident that telehealth methodology, by video-conferencing, is as much reliable as the face to face modality. The small number of the subjects evaluated represents an obvious limitation of this study and suggests further studies involving larger number of subjects. However, our preliminary results give support to the idea that by tehealth the screening and the follow-up of the cognitive impairments age associated is feasible and valid.

BACKGROUND: Telemedicine consists in the use of telecommunication technologies to provide healthcare services overcoming geographic, temporal, social, and cultural barriers. Today telemedicine is a developed field, which includes about 50 different subspecialties: neuropsychology is one of them. Its main application consists in the early diagnosis of cognitive disorders of adult onset ,and particularly in the assessment of individuals potentially affected by degenerative conditions, such as Alzheimer disease (AD). These individuals would benefit significantly by an assessment by telemedicine. This study was aimed to assess the feasibility by telemedicine of two widely used neuropsychological test: the MMSE and the ADAS_COG test. While for the first some data are available in the literature, no study has investigated, to our knowledge, the ADAS_COG administration by videoconference in subjects with AD. We aimed thus to compare the results obtained by the ''face to face'' condition to those obtained by videoconference. MATERIALS AND METHODS: The ADAS_Cog and the MMSE test were administered to 28 subjects (8M) in two conditions: the face-to-face condition and the video-conference modality. Subjects were all participating to the randomized, double blind, placebo controlled ASCOMALVA study. The administration was done at the enrollment of the patients in the study, baseline, and after 6, 12, 18 and 24 months. Subjects were randomized in two groups. Group A subjects were submitted to the ADAS_Cog and the MMSE test by the face-to-face modality first; two weeks later the same tests were administered via telemedicine by videoconferencing. Group B were submitted vice-versa to the videoconference modality first, and then to the face to face. A two-tailed Student "t" test was done to evaluate the differences between the two modality. RESULTS: There was no significant difference in MMSE scores and ADAS_Cog scores (p minus .05) administered by telehealth versus face to face modality. In patient with moderate AD the administration via telemedicine gives worse results on average than the face to face mode CONCLUSIONS: The most employed tool to assess and measure the cognitive functions in subjects potentially affected by degenerative dementia are the MMSE and the ADAS_Cog. Both are required in the clinical trials to assess the severity of the damage and the effectiveness of new drugs. Their employ by videoconference should be very useful. We found that both the MMSE and the ADAS Cog test may be applied in subjects with mild to moderate Alzheimer disease, and that the scores obtained by videoconference are related to those obtained by the face to face condition. Videoconference may be very useful to reach patients with cognitive damages, to assess their stability or progression, to measure the efficacy of therapies.

Nei mammiferi si possono distinguere due tipi di tessuto adiposo che collaborando per un fine strategico e funzionale costituiscono l’ Organo Adiposo. Questi due tessuti sono il bianco (WAT) ed il bruno (BAT). Il BAT e’ specializzato nella produzione di calore, mentre il WAT e’ necessario all’ organismo per conservare energia in eccesso sottoforma di trigliceridi . L’ acclimatazione a freddo induce un incremento della componente bruna, senza modificare il numero totale di cellule. Questa forma di plasticita’ cellulare fino ad ora e’ stata associata a modelli animali che possiedono resistenza all’obesita’ ed al diabete. In questo lavoro e’ stato effettuato uno studio anatomico di topi adulti C57BL/6J (B6), linea molto sensibile allo sviluppo della sindrome metabolica con obesita’, iperglicemia e insulinoresistenza se alimentati con HFD . Lo scopo e’ stato quello di verificare la percentuale di adipociti bianchi e bruni di tutti i depositi che compongono l’Organo Adiposo di questo ceppo a 28°C (gruppo di controllo) ed a 6°C. Inoltre e’ stato verificato lo stato termogenico degli adipociti ML tramite l’espressione della proteina UCP1 ed effettuato uno studio sistematico sul numero di fibre noradrenergiche parenchimali TH (Tirosina idrossilasi) positive. La composizione cellulare di tutti i depositi era mista, con entrambi i citotipi rappresentati, non ne sono stati trovati di completamente puri. Questo dato conferma l’ esistenza di un Organo Adiposo . Nei controlli il 77% degli adipociti era UL, mentre negli animali acclimatati a freddo sono piu’ numerose le ML, che rappresentano il 60% di tutti gli adipociti, di questi il 79% era immunoreattivo per l’ anticorpo UCP1. Dopo l’esposizione a 6°C il numero totale di adipociti nell’ organo adiposo non era cambiato, il numero di ML era incrementato in modo significativo (+ 37% p =0.011) e il numero di UL era diminuito approssimativamente della stessa proporzione (- 41% p= 0.05). Non e’ stata trovata nessuna evidenza di apoptosi tra gli adipociti bianchi. Questi dati documentano una plasticita’ dell’ organo adiposo dei B6 che e’ stata osservata maggiormente nel deposito sottocutaneo anteriore (ASC) e nell’ addomino pelvico (AP), mentre in uno studio effettuato in passato su un ceppo piu’ resistente all’ obesita’ (SV129), che presentava una maggior quantita’ di ML sia a caldo che a freddo i depositi piu’ trasformati erano il sottocutaneo posteriore (PSC) ed il mesenterico (MES). La proteina UCP1 che riflette l’attivazione della termogenesi (non shivering) a freddo e’ espressa nel 34% degli adipociti bruni dei controlli, il loro numero incrementa significativamente a 6°C (79% p=0,02). L’ aumento dell’ espressione di UCP1 correla positivamente con quella della Tirosina-idrossilasi (TH), soprattutto negli animali esposti a freddo, suggerendo un ruolo fondamentale del sistema nervoso nella trasformazione dell’ organo adiposo. In molti depositi dei C57BL sia a caldo, ma soprattutto dopo acclimatazione a 6°C sono state osservate molte cellule “Pauciloculari”. In questa linea, come nei 129SV il volume totale dell’ organo si riduce e questo e’giustificato da una diminuzione di volume anche degli adipociti UL ed ML. Complessivamente tutte queste osservazioni suggeriscono un processo di Transdifferenziazione degli adipociti bianchi in adipociti bruni nei topi acclimatati a freddo, confermando quanto gia’ osservato nella linea SV129. concludendo possiamo affermare che la plasticita’ dell’ organo adiposo e’ indipendente dal background genetico, che invece potrebbe influire nel cambiamento di alcuni depositi piuttosto che altri.
In mammals, two functionally different type of adipose tissues are contained in a multi-depot organ: the adipose organ. It consists of several subcutaneous and visceral depots. Some areas of these depots are brown and correspond to brown adipose tissue, wich is specialized in energy expenditure, while many are white and correspond to white adipose tissue, the primary site of triglyceride storage. Cold acclimatisation induces an increase in the brown component without affecting the overall number of adipocytes; so far this form of plasticity was associated to obesity and diabetes resistance in experimental models. In this work we performed an anatomical study of adult C57BL/6J mice, which on HFD develop severe obesity, hyperglycemia and isulin resistance. The aim of this work was to check the percentage of white and brown adipocytes of all fat depots that make up the adipose organ of this strain at 28 ° C (control group) and 6 ° C. Was also monitored the thermogenic status of ML adipocytes through the expression of UCP1 protein and carried out a systematic study on the number of tyrosine hydroxylase parenchymal (noradrenergic)-positive nerve fibers (no. of fibers per 100 adipocytes). The cellular composition of all depots was mixed, with both cellular populations represented, there are not completely pure. This shows the existence of an adipose organ also in C57BL/6J. In the control animals the prevalent cell type were withe adipocytes (77% of all adipocytes), conversely in the cold-acclimated mice there was a prevalence of brown adipocytes (60% of all adipocytes); of these the 79% were immunoreactive for UCP1 antibody. After cold acclimation the total number of adipocytes in the adipose organ was unchanged, the number of brown adipocytes increased significantly (+37% p = 0.011) and the number of white adipocytes decreased by approximately the same amount (-41% p= 0.05). No evidence of apoptosis of white adipocytes was detected. The most prominent differences in cell composition (adipocyte plasticity) were found in the anterior subcutaneous (ASC) and in the abdomino- pelvic depots (AP). In a study conducted in 2005 on strain considered resistant to dietary induced obesity (SV129), was observed that the adipose organ contained a greater amount of ML in both conditions (28 ° C and 6 ° C) and the most changed depots were posterior subcutaneous (PSC) and the mesenteric (MES). In the control group the thermogenic protein UCP1 was expressed only in 34% of ML adipocyes, but their number increase significantly after cold exposure (79% p=0,02). The proportion of brown adipocytes UCP1+ is positively correlated with noradrenergic fiber density especially in the cold-acclimated mice, suggesting a crucial role of nervous system on the changes of the adipose organ after cold exposure. In many depots of C57BL (both 28°C and 6°C),especially after cold acclimation were observed Paucilocular cells (the “transdifferentiation marker”). In In this strain, like in SV129 the adipose organ shrank in volume; this reduction corresponded to the volume reduction of each brown and white adipocyte. Overall, these modifications of the adipose organ suggest a process of transdifferentiation of white into brown adipocytes in cold-acclimated mice confirming what was observed in the SV129 mice. In conclusion we can affirm that the phenotypic plasticity of the whole adipose organ is independent of genetic background, that could affect a greater change in a depot rather than in another .

E’ ben noto come i disturbi metabolici si associno all’obesità quasi esclusivamente quando l’obesità è di tipo viscerale. Ovvero quando i depositi adiposi che si espandono sono principalmente quelli viscerali. Il nostro gruppo ha dimostrato che il 90% dei macrofagi nel WAT dei soggetti obesi si dispone in maniera circolare attorno agli adipociti morti a formare strutture denominare CLS (crown-like structures). Inoltre, abbiamo recentemente osservato che, pur essendo valida la correlazione positiva tra dimensione degli adipociti e densità delle CLS (indice dell’ infiammazione) sia nel grasso viscerale che nel grasso sottocutaneo, negli animali geneticamente obesi, il grasso viscerale presenta una maggiore densità di CLS pur avendo adipociti più piccoli. Questa osservazione suggerisce che gli adipociti viscerali e i sottocutanei presentano una diversa predisposizione alla morte. L’infiltrazione macrofagica che caratterizza l’organo adiposo di soggetti obesi determina uno stato di infiammazione cronica di basso grado che genera insulino resistenza e diabete di tipo 2. In questo studio abbiamo valutato l’espressione di fattori associati allo stato d’infiammazione del tessuto adiposo e la presenza di alterazioni ultrastrutturali nelle cellule adipose dei depositi sottocutanei e viscerali di due modelli di obesità genetica (topi ob/ob e db/db). Nei due ceppi di topi, l’analisi immunoistochimica per PJNK e NF-kB (molecole associate ad infiammazione cronica) ha evidenziato l'espressione di entrambe le proteine da parte dei macrofagi che formano le CLS suggerendo che proprio queste strutture potrebbero essere la principale fonte di P-JNK e NF-kB. Lo studio degli aspetti ultrastrutturali ha evidenziato una riduzione dello spessore citoplasmatico, dell’area media dei mitocondri e della percentuale di superficie citoplasmatica libera da gocce lipidiche occupata dai mitocondri; queste alterazioni sono significative solo nei depositi viscerali, sito prevalente della morte adipocitaria e della conseguente formazione delle CLS. Questi dati confermano l’esistenza di una correlazione fra accumulo di grasso viscerale e incidenza dei disturbi associati all’obesità e suggeriscono che interventi mirati a ridurre lo stato di infiammazione del tessuto adiposo, impedendo il processo di ipertrofia adipocitaria e la conseguente morte degli adipociti, potrebbero rappresentare un promettente approccio per la prevenzione della Sindrome Metabolica.
It is well known that metabolic disorders are associated almost exclusively with obesity in the case of is visceral obesity. That is when the fat depots wich expand are mainly visceral. Our group has shown that 90% of macrophages in WAT of obese individuals surround the dead adipocytes forming structures called CLS (crown-like structures). In addition, we recently observed that, although an significant positive correlation exists between adipocyte size and CLS density (index of inflammation) in visceral and in subcutaneous depots, in genetically obese animals, visceral depot has a greater density of CLS although adipocytes are smaller, suggesting that visceral and subcutaneous adipocytes have a different susceptibility to death. The macrophage infiltration characterizing the adipose organ of obese subjects results in a state of chronic low-grade inflammation that produces insulin resistance and type 2 diabetes. In this study we evaluated the expression of factors associated with the adipose tissue inflammation state and the presence of ultrastructural alterations in adipocytes of subcutaneous and visceral depots of two genetic models of obesity (ob/ob mice and db/db). In both strains, immunohistochemistry analysis for NF-kB and PJNK (molecules associated with chronic inflammation) showed the expression of both proteins by macrophages that form the CLS suggesting that these structures could be the main source of P-JNK and NF-kB. The analysis of ultrastructural aspects showed a reduction of the cytoplasm thickness, mitochondria area, and of the percentage of free lipid droplets cytoplasmic area occupied by mitochondria; these alterations are significant only in the visceral depots, the main site of adipocyte death and the consequent formation of CLS. These data confirm the well known association between the accumulation of visceral fat and incidence of disorders associated with obesity and suggest that interventions aimed at reducing the state of inflammation of adipose tissue, by preventing the adipocyte hypertrophy process and the subsequent death of adipocytes, may represent a promising approach for the prevention of the metabolic syndrome.

Una delle conseguenze più comuni dell’ obesità, soprattutto dell’ obesità viscerale, è l’insorgenza nell’adulto del diabete mellito di tipo 2. Recenti studi suggeriscono che esso sia dovuto ad uno stato di lieve infiammazione cronica dell’ organo adiposo. Si è visto che l’organo adiposo degli obesi è infiltrato da macrofagi che producono citochine (soprattutto TNF-e IL-6) che sembrano essere responsabili dell’ insorgenza dell’ insulino resistenza che precede il diabete mellito di tipo 2. Queste citochine infatti, interferiscono con il substrato 1 del recettore insulinico rendendolo meno efficiente. E’ stato recentemente dimostrato che la grande maggioranza dei macrofagi che infiltrano il grasso si dispongono attorno agli adipociti morti formando strutture caratteristiche denominate “crown-like structures”. Questo fenomeno potrebbe essere causato da un’ eccessiva espansione degli adipociti obesi. Gli adipociti viscerali sembrano più suscettibili a questo tipo di morte offrendo una possibile spiegazione agli effetti più morbigeni dell’ accumulo di grasso viscerale. L’ ipotesi generalmente accettata per spiegare l’ insorgenza del diabete mellito di tipo 2 è che la resistenza insulinica comporti la necessità di una iperproduzione di insulina pancreatica che a lungo andare esaurisce la capacità compensativa delle isole di Langerhans sfociando quindi nel diabete franco. A causa dell’ espansione epidemica dell’ obesità, negli ultimi anni si è diffusa notevolmente la pratica del trattamento chirurgico di questa condizione morbosa. La chirurgia bariatrica negli Stati Uniti costituisce la prima causa di intervento chirurgico. L’ operazione di by-pass intestinale ha evidenziato un risultato inatteso sia nell’ uomo che in condizioni sperimentali: il miglioramento del diabete nei soggetti operati prima della perdita di peso. Questo suggerisce nuovi meccanismi che portano dalla resistenza insulinica alla franca condizione diabetica in quanto la modifica anatomica indotta dalla chirurgia ripristina la secrezione insulinica, suggerendo che vi sia una fase di inibizione della secrezione che precede la perdita di materiale delle cellule  nel pancreas. In questa tesi abbiamo indagato le isole di Langerhans in topi geneticamente obesi (ob/ob - privi di leptina; db/db – privi del recettore leptinico) e in topi indotti all’obesità madiante dieta grassa (HFD) a 15 settimane di età, per verificare se vi siano condizioni strutturali in grado di spiegare il meccanismo attraverso il quale la chirurgia bariatrica è in grado di migliorare in modo acuto e prima del calo ponderale, il metabolismo glucidico compromesso dalla condizione di obesità. I nostri risultati indicano che parallelamente all’ incremento di peso che insorge negli animali obesi, si assiste ad una progressiva ipertrofia e iperplasia delle isole di Langerhans (fase di compenso alla resistenza insulinica) soprattutto nei topi geneticamente modificati. A questo si accompagna un incremento dell’ insulino-resistenza che sfocia nel diabete franco come avviene nei topi db/db. Il diabete insorge prima di una evidente perdita di sostanza a livello delle isole di Langerhans suggerendo una fase di inibizione della secrezione insulinica. Il fenomeno assume maggiore gravità negli animali db/db rispetto agli ob/ob e agli HFD. L’ analisi delle isole rivela due aspetti che possono spiegare una progressiva inibizione della secrezione insulinica: il significativo e progressivo aumento dell’ innervazione parenchimale delle isole di Langerhans da parte di fibre adrenergiche (tirosina-idrossilasi immunoreattive) e la redistribuzione di elementi cellulari intrainsulari immunoreattivi per il neuopeptide Y (NPY). Entrambi questi aspetti possono indicare una progressiva inibizione della secrezione insulinica prima che intervengano fenomeni apoptotici in grado di determinare un esaurimento anatomico della secrezione insulinica. Questi dati suggeriscono quindi l’ipotesi che la chirurgia bariatrica possa promuovere meccanismi citofisiologici a partenza intestinale in grado di rimuovere tali aspetti inibitori. Inoltre, la presenza di cellule chemo-sensitive del primo tratto della parete intestinale suggerisce che tali elementi potrebbero essere implicati nel determinare il fenomeno inibitorio.
Among the most common consequences of the obesity, especially of visceral obesity, there is the onset of type 2 diabetes mellitus in adults. Recent studies suggest that this condition is due to a state of mild chronic inflammation of adipose organ. It has been shown that the body fat of obese subjects is infiltrated by macrophages that appear toproduce cytokines (especially TNF- and IL-6) responsible for the insurgence of insulin resistance that precedes type 2 diabetes mellitus. Indeed, they interfere with the insulin receptor substrate 1, making it less efficient. It has been recently shown that the vast majority of macrophages that infiltrate adipose tissue localize around dead adipocytes, forming characteristic structures known as "crown-like structures". This phenomenon could be caused by an over-expansion of obese adipocytes. Visceral adipocytes seem to be more susceptible to this kind of death by providing a possible explanation of dangerous effects of visceral fat accumulation. The widely accepted hypothesis to explain the onset of type 2 diabetes, is that insulin resistance results from the need of a pancreatic overproduction of insulin that eventually exhausts the compensatory capacity of the islets of Langerhans finally leading to frank diabetes. Because of the growing epidemic of obesity, in the last years the surgical practice for the treatment of this disease has significantly spread. Bariatric surgery in the United States is the main cause of surgery. Unexpectedly the intestinal bypass operation in humans and in experimental models results in the improvement of diabetes in patients that underwent surgery before weight loss. The fact that the anatomical changes induced by surgery are able to restore insulin secretion provides further explanations for the mechanisms responsible for the shift from the condition of insulin resistance to that of frank diabetes by suggesting the occurrence of a phase of insulin secretion inhibition preceding the loss of material in the cells of Langerhans. In this study we investigated the islets of Langerhans both in genetically modified obese mice (ob/ob : no leptin; db/db: leptin receptor-free) and mice with obesity induced by high - fat diet (HFD) at 15 weeks of age, to assess the existence of structural conditions that could explain the mechanism by which bariatric surgery can improve acutely the impaired glucose metabolism of obese subjects and before the weight loss. Our results indicate that in parallel to 'weight gain that occurs in obese animals, a progressive hypertrophy and hyperplasia of the islets of Langerhans (phase compensation to insulin resistance) occurs, especially in genetically modified mice. This is accompanied by an increase of insulin resistance that in mice leads to frank diabetes as we observed in db/db mice. The occurrence of diabetes before an evident loss of substance in the islets of Langerhans suggests the evidence of a phase of inhibition of insulin secretion. The phenomenon is more severe in db / db mice compared with ob / ob and the HFD mice. The analysis of the islets revealed two aspects that could explain a progressive inhibition of insulin secretion: the significant and progressive increase of' parenchymal innervation of the islets of Langerhans by adrenergic fibers (tyrosine hydroxylase, TH - immunoreactive) and the redistribution of cellular intrainsular elements that are immunoreactive for neuopeptide Y (NPY). Both these aspects indicate that a progressive inhibition of insulin secretion possibly occurs before apoptosis leading to a depletion of anatomical insulin secretion. These data provide the hypothesis that bariatric surgery could promote cytophysiological intestinal mechanisms through the removal of those inhibitory elements. In addition, the presence of chemo-sensitive cells in the first section of the bowel wall suggests that these factors may be involved in determining the inhibitory phenomenon.

Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) is an autoimmune disease characterized by the production of brain-reactive autoantibodies. These autoantibodies are thought to be one of the main mediators of this condition, however little is known about their cellular and molecular target. To get inside this matter, we enrolled a cohort of 209 subjects including patients affected by Systemic Lupus Erythematosus (SLE, n=69), NPSLE (drug-naïve, n=36), multiple sclerosis (MS, n=22) as well as 82 age and gender matched healthy subjects. Sera from these subjects were used for immunostaining on rat brain through fluorescence microscopy and TEM, in parallel with immunofluorescence on human brain sections and cells (SH-SY5Y) to eventually confirm the results obtained in rat. As to the brain autoantibody target, western blot (WB) using wild type and transfected HEK293 cells, which do or do not express the RBFOXP3 gene (encoding the NeuN protein). Furthermore, ELISA was programmed to reveal the possible presence of the known circulating autoantibodies in SLE (anti: -Ro/SSA, -La/SSB, -RNP, -Sm, and -Rib-P) and autoantibodies to the aminoacidic sequence DWEYS. On rat brain sections, we observed autoantibody positive reaction in several areas (cortex, hippocampus, cerebellum, and others) exclusively using sera from patients with NPSLE and SLE but with prevalence and higher titer among the NPSLE patients (77,1% vs. 56,5%, respectively and 1:2,000-8,000 vs. 1:120-1,000, respectively). In order to consolidate the results obtained in rats, negative and positive sera from SLE and NPLSE patients as well as healthy and MS controls were selected (n=6) to be tested in human hippocampus and cerebellum sections. Autoantibody reactivity was found only using those sera positively reacting on rat tissues. Through ELISA, anti: -Ro/SSA, -La/SSB, -RNP, -Sm, -Rib-P and -DWEYS were found using rat-immunostained-positive sera from both NPSLE and SLE patients. In both patients’ populations, the presence of one or more types of these autoantibodies was not higher than 31,6% while a percentage was negative for all the above autoantibodies (17,9% and 31,6%, in NPSLE and SLE respectively). Hence, the presence of these autoantibodies could confirm only partially the reactivity according to the immunostaining results. In the rat cerebellum, the autoantibodies stained a cytoplasmic area also in proximity of the nucleus (namely perinuclear/cytoplasmatic pattern) or inside the nucleus (namely intranuclear pattern), both revealed using either fluorescence microscopy or TEM. In order to identify the cell type recognized by the autoantibodies in the cerebellum, we performed double staining, mixing the sera from patients with the antibody to NeuN (known to mark the granule cells), as well as antibodies to VGlut1, VAChT or GAD-65, marking glutamatergic axon terminals, cholinergic and GABAergic neurons, respectively. Autoantibody staining was localized exclusively within NeuN containing cells. Autoantibodies labelled NeuN containing neurons also in many other areas of the brain. We performed WB experiments to reveal NeuN as possible autoepitope using either wild type and transfected HEK293 cells, which do not or do express the RBFOXP3 gene, respectively. The patient’s sera never recognized the bands corresponding to the NeuN protein, despite these bands were labeled by the anti-NeuN antibody using transfected cells, proving that NeuN was not the autoantibody target. In conclusion, all together the da-ta obtained from this study demonstrate that (1) SLE and NPSLE could possess a mix of different types of autoantibodies reacting to neuronal cells (2) the entire brain could be the target of these autoantibodies (3) a high prevalence of brain reactive autoantibodies is found among NPLSE patients and (4) autoantibodies could react to the nucleus and/or cytoplasm of brain neuron cells.