[BODY AND CORPORALITY IN THE HUMAN BEING: SOME INTERDISCIPLINARY REFLECTIONS]. / CUERPO Y CORPORALIDAD EN EL HOMBRE: ALGUNAS REFLEXIONES INTERDISCIPLINARES.

The major purpose of this contribution is to illustrate some differential aspects between the human and the animal bodies, in order to understand the main distinctive characteristic of the human being: his or her rationality. Thus, we firstly deal with some considerations about the general anthropological framework in which the human body is going to be analysed. Next, we briefly explain the importance of the body for an adequate understanding of the intimacy and the biographical perspectives of the person. Here we show some examples of the altered human corporality to stress the importance of the relation to oneself and others as a key and fundamental aspect to look at our rational corporality.

Distribution of GABAergic interneurons and dopaminergic cells in the functional territories of the human striatum.

BACKGROUND: The afferent projections of the striatum (caudate nucleus and putamen) are segregated in three territories: associative, sensorimotor and limbic. Striatal interneurons are in part responsible for the integration of these different types of information. Among them, GABAergic interneurons are the most abundant, and can be sorted in three populations according to their content in the calcium binding proteins calretinin (CR), parvalbumin (PV) and calbindin (CB). Conversely, striatal dopaminergic cells (whose role as interneurons is still unclear) are scarce. This study aims to analyze the interneuron distribution in the striatal functional territories, as well as their organization regarding to the striosomal compartment. METHODOLOGY/PRINCIPAL FINDINGS: We used immunohistochemical methods to visualize CR, PV, CB and tyrosine hydroxylase (TH) positive striatal neurons. The interneuronal distribution was assessed by stereological methods applied to every striatal functional territory. Considering the four cell groups altogether, their density was higher in the associative (2120±91 cells/mm(3)) than in the sensorimotor (959±47 cells/mm(3)) or limbic (633±119 cells/mm(3)) territories. CB- and TH-immunoreactive(-ir) cells were distributed rather homogeneously in the three striatal territories. However, the density of CR and PV interneurons were more abundant in the associative and sensorimotor striatum, respectively. Regarding to their compartmental organization, CR-ir interneurons were frequently found in the border between compartments in the associative and sensorimotor territories, and CB-ir interneurons abounded at the striosome/matrix border in the sensorimotor domain. CONCLUSIONS/SIGNIFICANCE: The present study demonstrates that the architecture of the human striatum in terms of its interneuron composition varies in its three functional territories. Furthermore, our data highlight the importance of CR-ir striatal interneurons in the integration of associative information, and the selective role of PV-ir interneurons in the motor territory. On the other hand, the low density of dopaminergic cells casts doubts about their role in the normal human striatum.

Structural brain abnormalities in first-episode psychosis: differences between affective psychoses and schizophrenia and relationship to clinical outcome.

OBJECTIVES: Several studies have described volumetric brain abnormalities in first-episode psychosis. The extent to which these differ in patients with schizophrenia and affective psychoses, or are related to subsequent clinical outcome, is unclear. We examined volumetric magnetic resonance imaging (MRI) abnormalities in young patients with a first episode of psychosis, and compared these volumetric abnormalities in patients with schizophrenia versus affective psychosis. We then assessed whether baseline MRI abnormalities in the entire sample predicted subsequent clinical outcome. METHODS: A total of 28 adolescent patients with first-episode psychosis and 20 age-matched healthy volunteers were scanned using a 1.5 T scanner. MRI data were processed and analysed using voxel-based morphometry (VBM). We assessed clinical outcome three years after the initial scan. RESULTS: Patients had smaller grey matter (GM) volumes than controls in frontal, insular, parietal, and cerebellar cortex. Patients with an affective psychosis had greater GM volume in the right posterior cingulate than both controls and patients with schizophrenia, but less GM volume in the left cerebellum and insula. In the sample as a whole, smaller right hippocampus GM volume was associated with poor clinical outcome at three-year follow-up. CONCLUSIONS: Volumetric brain abnormalities are evident in young adults presenting with a first episode of both affective psychoses and schizophrenia, but there are also significant differences between these two patient groups. Clinical outcome after the first episode may be related to the severity of volumetric abnormalities at presentation.

[A nuclear document in the central core of the moral debates of our time]. / Un Documento Nuclear en los Debates Morales de Nuestro Tiempo.

We summarize the contents of the Instruction Dignitas personae and briefly attempt to explain why we find ourselves before an impossible debate when we talk about human life, its conception and reception. We will also try to provide some light as we try to escape this cul de sac so characteristic in the moral discussions of our time. To do so, we seek the help of the moral philosopher, Alasdair MacIntyre, whose life's work makes him especially suited to identifying the anthropological paradoxes that we are facing nowadays and which are very much related to the different issues mentioned in the Instruction.

[Neural mechanisms of attachment behaviors and pregnancy]. / Neurobiología del "vínculo de apego" y embarazo.

Functional neuroimage techniques show how certain brain areas are activated, while others become silent, when a mother sees her child or hears his/her voice. This is the neural correlate of the emotion, which the presence of her child generates, under diverse circumstances, in the mother. Brain is organised to mediate the complex maternal behaviour. For that, gene expression is orchestrated by different hormonal and neurochemicals factors of pregnancy. Maternal behaviors might be reasonably well characterized in terms of cognitive-emotional interactions and brain amygdala function is their cognitive-emotional connector hub.

The mediodorsal thalamic nucleus and schizophrenia.

The mediodorsal nucleus of the human thalamus is in a crucial position that allows it to establish connections with diverse cerebral structures, particularly the prefrontal cortex. The present review examines existing neurobiologic studies of the brains of people with and without schizophrenia that indicate a possible involvement of the mediodorsal nucleus in this psychiatric disorder. Studies at synaptic and cellular levels of the neurobiology of the mediodorsal nucleus, together with a better anatomic understanding of this diencephalic structure owing to neuroimaging studies, should help to establish a more deep and solid pathophysiologic model of schizophrenia.

A new antigen retrieval technique for human brain tissue.

Immunohistochemical staining of tissues is a powerful tool used to delineate the presence or absence of an antigen. During the last 30 years, antigen visualization in human brain tissue has been significantly limited by the masking effect of fixatives. In the present study, we have used a new method for antigen retrieval in formalin-fixed human brain tissue and examined the effectiveness of this protocol to reveal masked antigens in tissues with both short and long formalin fixation times. This new method, which is based on the use of citraconic acid, has not been previously utilized in brain tissue although it has been employed in various other tissues such as tonsil, ovary, skin, lymph node, stomach, breast, colon, lung and thymus. Thus, we reported here a novel method to carry out immunohistochemical studies in free-floating human brain sections. Since fixation of brain tissue specimens in formaldehyde is a commonly method used in brain banks, this new antigen retrieval method could facilitate immunohistochemical studies of brains with prolonged formalin fixation times.

[Chemical anatomy of the thalamus in the schizophrenia]. / Anatomía química del tálamo en la esquizofrenia.

The thalamus is considered nowadays as a key structure in the whole organization of the cortico-subcortical relationships. In the last few years, there has been a growing interest in analyzing the potential alterations that could occur in this diencephalic structure in certain psychiatric disorders, prominently in the schizophrenia. In this contribution we describe some of the results obtained in various studies focused on the synaptic modifications of the thalamus observed in schizophrenic patients.

Cholinergic interneurons are differentially distributed in the human striatum.

BACKGROUND: The striatum (caudate nucleus, CN, and putamen, Put) is a group of subcortical nuclei involved in planning and executing voluntary movements as well as in cognitive processes. Its neuronal composition includes projection neurons, which connect the striatum with other structures, and interneurons, whose main roles are maintaining the striatal organization and the regulation of the projection neurons. The unique electrophysiological and functional properties of the cholinergic interneurons give them a crucial modulating function on the overall striatal response. METHODOLOGY/PRINCIPLE FINDINGS: This study was carried out using stereological methods to examine the volume and density (cells/mm(3)) of these interneurons, as visualized by choline acetyltransferase (ChAT) immunoreactivity, in the following territories of the CN and Put of nine normal human brains: 1) precommissural head; 2) postcommissural head; 3) body; 4) gyrus and 5) tail of the CN; 6) precommissural and 7) postcommissural Put. The distribution of ChAT interneurons was analyzed with respect to the topographical, functional and chemical territories of the dorsal striatum. The CN was more densely populated by cholinergic neurons than the Put, and their density increased along the anteroposterior axis of the striatum with the CN body having the highest neuronal density. The associative territory of the dorsal striatum was by far the most densely populated. The striosomes of the CN precommissural head and the postcommissural Put contained the greatest number of ChAT-ir interneurons. The intrastriosomal ChAT-ir neurons were abundant on the periphery of the striosomes throughout the striatum. CONCLUSIONS/SIGNIFICANCE: All these data reveal that cholinergic interneurons are differentially distributed in the distinct topographical and functional territories of the human dorsal striatum, as well as in its chemical compartments. This heterogeneity may indicate that the posterior aspects of the CN require a special integration of information by interneurons. Interestingly, these striatal regions have been very much left out in functional studies.

Heterogeneidad morfológica de la porción posterior del estriado humano / Morphological heterogeneity of the human posterior striatum

El estriado (núcleo caudado, NC, y putamen, Put) forma parte de los gangliosbasales, un conjunto de núcleos subcorticales cuya principal función es la planificacióny ejecución de los movimientos voluntarios. La información nerviosa procedentede la corteza cerebral alcanza el estriado formando tres canales distintos,denominados asociativo, sensorimotor y límbico. La parte posterior del estriado,que incluye el cuerpo, el giro y la cola del NC, además del último tercio del Putpostcomisural, ha recibido una escasa atención en cuanto a sus característicasquímicas y composición celular. El presente trabajo tiene como objetivo analizarla distribución de dos poblaciones de interneuronas (nitrérgicas y colinérgicas) en la parte posterior del estriado. Según nuestros resultados, ambas poblaciones presentanuna mayor densidad en la parte posterior del estriado que en la parteanterior, siendo más abundantes en el NC que en el Put. La región más densamentepoblada por las neuronas nitrérgicas es el giro del NC, mientras que las neuronascolinérgicas son especialmente abundantes en el cuerpo de dicho núcleo.Además, la organización de los dos grupos neuronales con respecto al compartimentoestriosomal es diferente en la parte posterior del estriado que en las regionesanteriores, y también varía según se trate de las neuronas nitrérgicas o de lascolinérgicas. En definitiva, nuestro estudio demuestra que la porción posterior delestriado puede llevar a cabo un procesamiento de la información tanto o máscomplejo que la parte anterior

The striatum (caudate nucleus, NC and putamen, Put) is a main part of thebasal ganglia, a group of subcortical nuclei whose main function is the planningand execution of voluntary movements. Nervous inputs from the cerebral cortexare divided into three different channels in the striatum, termed associative, sensorimotorand limbic. The posterior aspect of the striatum comprises the body,gyrus and tail of the NC, and the postcommissural Put, and has been very muchleft out of most of chemical and cellular studies. The present work is aimed atanalyzing the distribution of two populations of interneurons (nitrergic and cholinergic)in those striatal regions. According to our results, both populations aremore abundant in the posterior striatum than in its anterior aspects, with a higherdensity in the NC than in the Put. The gyrus of NC is the most populated regionby nitrergic cells, whereas cholinergic interneurons are especially abundant in thebody of NC. Furthermore, the organization of both interneuronal groups regardingthe striosomal compartment is different in the posterior striatum with respect toits anterior aspects, and this organization also varied when nitrergic or cholinergicinterneurons were analyzed. Overall, our study demonstrates that the posterioraspect of the striatum might carry out a more complex processing of the informationthan its anterior counterpart

Expression of excitatory amino acid transporter interacting protein transcripts in the thalamus in schizophrenia.

The excitatory amino acid transporters (EAATs) are a family of plasma membrane proteins that maintain synaptic glutamate concentration by removing glutamate from the synaptic cleft. EAATs are expressed by glia (EAAT1 and EAAT2) and neurons (EAAT3 and EAAT4) throughout the brain. Glutamate reuptake is regulated, in part, by EAAT-interacting proteins that modulate subcellular localization and glutamate transport activity of the EAATs. Several lines of investigation support the hypothesis of glutamatergic abnormalities in schizophrenia. Previous work in our laboratory demonstrated increased expression of EAAT1 and EAAT2 transcripts in the thalamus, suggesting that alterations in synaptic glutamate levels may contribute to the pathophysiology of schizophrenia. Since EAAT-interacting proteins regulate EAAT function, directly impacting glutamatergic neurotransmission, we hypothesized that expression of EAAT-interacting proteins may also be altered in schizophrenia. Using in situ hybridization in subjects with schizophrenia and a comparison group, we detected increased expression of JWA and KIAA0302, molecules that regulate EAAT3 and EAAT4, respectively, in the thalamus in schizophrenia. In contrast, we did not find changes in the expression of transcripts for the EAAT2 and EAAT4 regulatory proteins GPS-1 and ARHGEF11. To address prior antipsychotic treatment in our schizophrenic subjects, we treated rats with haloperidol and clozapine for 4 weeks, and found changes in transcript expression of the EAAT-interacting proteins in clozapine-, but not haloperidol-, treated rats. These findings suggest that proteins associated with the regulation of glutamate reuptake may be abnormal in this illness, supporting the hypothesis of altered thalamic glutamatergic neurotransmission in schizophrenia.

Striatal projections from the lateral and posterior thalamic complexes. An anterograde tracer study in the cat.

Striatal projections from the lateral intermediate (LI) and posterior (Po) thalamic complexes were studied with the anterograde tracers wheat germ agglutinin-horseradish peroxidase and Phaseolus vulgaris leucoagglutinin. Projections to the lateral part of the head and body of the caudate nucleus (CN) and to the putamen (Pu) were found to arise from the ventral parts of the caudal subdivision of the LI besides the well established sources in the intralaminar and ventral thalamic nuclei. No projections to the CN and only a few to the Pu were found to arise from the medial division of the Po. The presence of terminal and intercalated varicosities in the thalamostriatal fibers suggests that they form both terminal and en passant synapses. Thalamostriatal fibers from these thalamic sectors were unevenly distributed within the CN, with patches of either low-density innervation or with no projections at all interspersed within irregular, more densely innervated areas. The former coincided with the acetylcholinesterase-poor striosomes and the latter areas of dense projection with the extrastriosomal matrix.

Morphological features, distribution and compartmental organization of the nicotinamide adenine dinucleotide phosphate reduced-diaphorase interneurons in the human striatum.

Striatal nicotinamide adenine dinucleotide phosphate reduced-diaphorase (NADPH-d)-positive (+) cells are one of the major classes of striatal interneurons. The present study analyzes their somatodendritic morphology, distribution pattern, and compartmental organization in the caudate nucleus (CN) and putamen (Put) of nine normal human brains. The following striatal territories are examined: 1) the precommissural head of the CN; 2) the postcommissural head of the CN; 3) the body of the CN; 4) the gyrus of the CN; 5) the tail of the CN; 6) the precommissural Put; and 7) the postcommissural Put. Three morphologically distinct types of NADPH-d+ neurons were found in each of these territories. The two most common NADPH-d+ neurons displayed an ovoid or triangular perikaryon from which several thick primary dendrites emerged, although much less numerous, bipolar-shaped NADPH-d+ cells were also observed. The highest density of NADPH-d+ neurons was found in the gyrus of the CN, followed by the body of the CN, tail of the CN, postcommissural head of the CN, postcommissural Put, precommissural head of the CN, and precommissural Put. The matrix was the striatal compartment with the densest NADPH-d+ neuronal population. Some of these cells also occurred in the center and peripheral regions of the striosomes located in the head of the CN and in the Put. In the body and gyrus of the CN, the striosomes were largely devoid of these striatal interneurons. Knowledge of the density and distribution of these interneurons should advance our understanding of the organization of the normal human striatum and help to evaluate the effects of neurodegenerative processes on cell density.

Changes in cytoskeletal gene expression linked to MPTP-treatment in Mice.

Parkinson's disease is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra and a marked reduction of dopamine (DA) levels in the striatum. Binding to its specific receptors, DA switches on a complex program of intracellular signaling that regulates gene expression. We evaluated the changes in striatal gene expression in a mouse model of Parkinson's disease, using differential display analysis. The mRNA for the cytoskeleton family proteins, radixin, cofilin and centractin/ARP-1, was abnormally expressed in the striatum of these MPTP-treated mice. Moreover, we also found that radixin mRNA and its protein levels are under DA control through specific D1-dopaminergic receptors in a dose- and time-dependent manner in the GT1-7 neural cell line. These findings suggest a role for DA for regulation of cytoskeletal proteins involved in the integrity and function of synapsis.

Chemical anatomy of the human paraventricular thalamic nucleus.

The paraventricular thalamic nucleus (Pa) lies in the most medial aspect of the thalamus and is considered one of the midline thalamic nuclei. In the present study, we carried out histochemical and immunohistochemical procedures in the Pa of normal individuals to visualize the pattern of distribution of acetylcholinesterase (AChE), calbindin D-28k (CB), parvalbumin (PV), calretinin (CR), limbic system-associated membrane protein (LAMP), substance P (SP), and enkephalin (ENK). Other cytoarchitectural and myeloarchitectural techniques, such as Nissl and Gallyas, were also employed to delineate the boundaries of the Pa. The main findings of this study are: 1) AChE staining in the Pa was heterogeneously distributed along its anteroposterior and mediolateral axes; 2) the Pa harbored numerous CB- and CR-immunoreactive (ir) cells and neuropil, but this nucleus was largely devoid of PV; 3) the Pa was highly enriched in LAMP and this protein appeared uniformly distributed through its whole extent; and, 4) the SP and ENK immunoreactivities in the Pa revealed numerous highly varicose fibers scattered throughout this nucleus, but no stained cells. This morphological study demonstrates that the Pa is a heterogeneous chemical structure in humans. The functional significance of these results is discussed in the light of similar data gathered in several mammalian species.

A re-examination of the striatal input from the mediodorsal thalamic nucleus in the rat / Una re-evaluación de la aferencia estriatal procedente del núcleo talámico mediodorsal de la rata

The projection from the mediodorsal thalamic nucleus to the striatum in the rat was studied by placing injections of the retrograde tracer Fluoro-Gold into the caudate putamen and small deposits of biotinylated dextran amine (BDA) into the mediodorsal thalamic nucleus. The relationship of thalamic afferent fibers with the compartmental organization of the striatum was studied by combining (BDA) tracing and enkephalin immunohistochemistry. The medial segment of the mediodorsal thalamic nucleus projects to the nucleus accumbens whereas the lateral segment projects sparsely to the medial regions of the caudate putamen. The caudal pole of the mediodorsal thalamic nucleus was found to project abundantly to ventrolateral regions of the precommissural caudate putamen, reaching areas of strong enkephalin immunoreactivity. The dorsolateral and caudal regions of the striatum did not receive projections from the mediodorsal thalamic nucleus. The present findings demonstrate a topographical organization of the thalamostriatal projections originating in the mediodorsal thalamic nucleus of the rat (AU)

La proyección desde el núcleo talámico mediodorsal al estriado en la rata fue investigada mediante inyecciones del trazador retrógrado fluoro-oro en el putamen caudal y pequeños depósitos de amino dextrano biotinilado (BDA) en el núcleo talámico mediodorsal. La relación entre las fibras talámicas eferentes y la organización compartimental se estudió combinando el trazado con BDA e inmunohistoquímica para encefalina. El segmento medial del núcleo talámico mediodorsal proyecta hacia el núcleo accumbens, mientras que el segmento lateral proyecta escasamente hacia las regiones mediales del putamen caudal. El polo caudal del núcleo talámico mediodorsal se vio que proyecta abundantemente hacia las regiones ventrolaterales del putamen caudal precomisural, alcanzando áreas de fuerte inmunorreactividad para la encefalina. Las regiones dorsolateral y caudal del estriado no recibían proyecciones procedentes del núcleo talámico mediodorsal. Los hallazgos de este estudio apuntan hacia una organización topográfica de las proyecciones talamo-estriatales que se originan en el núcleo talámico mediodorsal de la rata La proyección desde el núcleo talámico mediodorsal al estriado en la rata fue investigada mediante inyecciones del trazador retrógrado fluoro-oro en el putamen caudal y pequeños depósitos de amino dextrano biotinilado (BDA) en el núcleo talámico mediodorsal. La relación entre las fibras talámicas eferentes y la organización compartimental se estudió combinando el trazado con BDA e inmunohistoquímica para encefalina. El segmento medial del núcleo talámico mediodorsal proyecta hacia el núcleo accumbens, mientras que el segmento lateral proyecta escasamente hacia las regiones mediales del putamen caudal. El polo caudal del núcleo talámico mediodorsal se vio que proyecta abundantemente hacia las regiones ventrolaterales del putamen caudal precomisural, alcanzando áreas de fuerte inmunorreactividad para la encefalina. Las regiones dorsolateral y caudal del estriado no recibían proyecciones procedentes del núcleo talámico mediodorsal. Los hallazgos de este estudio apuntan hacia una organización topográfica de las proyecciones talamo-estriatales que se originan en el núcleo talámico mediodorsal de la rata (AU)