Cerebellar spongiform degeneration is accompanied by metabolic, cellular, and motor disruption in male rats with portacaval anastomosis.

The episodes of cerebral dysfunction, known as encephalopathy, are usually coincident with liver failure. The primary metabolic marker of liver diseases is the increase in blood ammonium, which promotes neuronal damage. In the present project, we used an experimental model of hepatic encephalopathy in male rats by portacaval anastomosis (PCA) surgery. Sham rats had a false operation. After 13 weeks of surgery, the most distinctive finding was vacuolar/spongiform neurodegeneration exclusively in the molecular layer of the cerebellum. This cerebellar damage was further characterized by metabolic, histopathological, and behavioral approaches. The results were as follows: (a) Cellular alterations, namely loss of Purkinje cells, morphological changes, such as swelling of astrocytes and Bergmann glia, and activation of microglia; (b) Cytotoxic edema, shown by an increase in aquaporin-4 and N-acetylaspartate and a reduction in taurine and choline-derivate osmolytes; (c) Metabolic adjustments, noted by the elevation of circulating ammonium, enhanced presence of glutamine synthetase, and increase in glutamine and creatine/phosphocreatine; (d) Inflammasome activation, detected by the elevation of the marker NLRP3 and microglial activation; (e) Locomotor deficits in PCA rats as assessed by the Rotarod and open field tests. These results lead us to suggest that metabolic disturbances associated with PCA can generate the cerebellar damage that is similar to morphophysiological modifications observed in amyloidogenic disorders. In conclusion, we have characterized a distinctive cerebellar multi-disruption accompanied by high levels of ammonium and associated with spongiform neurodegeneration in a model of hepatic hypofunctioning.

Procesamiento de la música en el primer episodio de trastorno depresivo mayor sin tratamiento / Music processing in major depressive disorder first episode without treatment

El propósito de este estudio fue registrar diferencias durante la audición de dos tipos diferentes de música en pacientes con Trastorno Depresivo Mayor (TDM), comparados con sujetos sanos, mediante imagen por resonancia magnética funcional (IRMf). La actividad cerebral con estímulos musicales ha sido investigada ampliamente en sujetos sanos, pero son escasos los estudios del procesamiento de la música en estados de patología mental, particularmente en el TDM. Los estudios en esta área interdisciplinaria proveen una nueva perspectiva de investigación para explorar los sustratos neurobiológicos del TDM. Participaron 20 sujetos de sexo masculino: 10 pacientes con TDM (34 ± 7 años) y 10 sujetos control (33 ± 7 años). Los pacientes se seleccionaron en el servicio de pre-consulta del Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz (INPRFM) de la Ciudad de México, y los sujetos control entre los trabajadores del propio Instituto que respondieron a la invitación. Todos los participantes contestaron, con fines de confirmar el diagnóstico, las escalas de ansiedad y depresión de Hamilton, los inventarios de Beck para ansiedad y depresión y el SCL-90-R. A los pacientes se les aplicó además el MINI-mental test. Para la IRMf se usó un equipo Philips Achieva de tres Teslas en el INPRFM, el análisis se hizo con el formato SPM2 usando el sistema MRIcro. Los estímulos experimentales fueron una obra musical de JS Bach validada como tranquila y otra de J Prodromidès validada como inquietante. Los resultados muestran diferencias tanto entre los grupos de sujetos como entre los tipos de música: en todos los casos se activó el área parahipocampal, la cola del núcleo caudado y la corteza temporal auditiva. Concluimos que el procesamiento neurobiológico de la música es afectado por el TDM. Se discuten las implicaciones clínicas y cognoscitivas de estos hallazgos.

The purpose of this study is the assessment of the differences in brain activity when patients with major depressive disorder (MDD) listen to two different types of music, with healthy subjects as control, by using functional magnetic resonance imaging (fMRI). Brain activity in musical stimuli with healthy subjects has been investigated extensively, but there are few neurobiologic music studies in mental illness, particularly in MDD. Studies in this area provide a new perspective on interdisciplinary research to explore the neurobiological substrates of MDD. This study involved 20 male subjects: 10 patients (34 ± 7 years), and 10 control subjects (33 ± 7 years). The MDD :atients were selected in the pre-consultation service of the National Institute of :sychiatry Ramón de la Fuente Muñiz (IN:RFM) of Mexico City, and control subjects were selected among workers of the Institute who responded to the invitation. All participants completed the Hamilton scales for anxiety and depression, Beck inventories for depression and anxiety and, the SCL-90-R. The Mini-Mental State Examination test was also administered to patients for diagnostic purposes. The fMRI was obtained by Philips Achieva 3-Tesla in the INPRF; the analysis was done using S:M2 format MRIcro system. The experimental stimuli were two pieces of music: one by JS Bach validated as quiet and another one by J Prodromidès validated as disturbing. Results show differences between both groups of subjects and between types of music. In all cases, the parahippocampal area, the tail of the caudate nucleus and the auditory temporal cortex were activated. The neurobiological processing of music is affected by MDD. We discuss the clinical and cognitive implications of these findings.

Espectroscopia cuantitativa de hidrógeno por resonancia magnética de 3 T en pacientes sintomáticos y asintomáticos con enfermedad de Huntington / Hydrogen magnetic resonance quantitative spectroscopy at 3 T in symptomatic and asymptomatic Huntington’s disease patients

Introducción. La enfermedad de Huntington es un trastorno neurodegenerativo hereditario autosómico dominante, caracterizado por síntomas motores, cognitivos y psiquiátricos. Objetivo. Determinar si existen diferencias en las concentraciones de N-acetilaspartato, creatina y compuestos que contienen colina (glucerilfosforilcolina y fosfocolina) en el núcleo caudado, el putamen y la corteza occipital de pacientes con enfermedad de Huntington, sintomáticos y asintomáticos. Sujetos y métodos. Se realizaron estudios de espectroscopia de hidrógeno por resonancia magnética en un equipo de 3 T a 10 individuos con prueba genética para enfermedad de Huntington, incluidos en tres grupos: negativos (control), positivos sintomáticos y positivos asintomáticos. Los estudios se cuantificaron con LCModel y se analizaron mediante análisis de varianza y prueba de Fisher. Resultados. Los pacientes sintomáticos mostraron disminución de creatina y N-acetilaspartato en las regiones estudiadas, y disminución de colina en el putamen (p < 0,05). En el núcleo caudado se encontró diferencia de colina entre sintomáticos y asintomáticos (p < 0,05). Conclusiones. Los resultados reflejan disfunción en el metabolismo neuronal y sugieren que la creatina y la colina, al ser marcadores de membrana, pueden comportarse en forma indirecta como marcadores de la evolución en la enfermedad de Huntington (AU)

Introduction. Huntington’s disease is an hereditary autosomic-dominant neurodegenerative disorder, characterized by motor, cognitive and psychiatric symptoms. Aim. To quantify differences in N-acetylaspartate, creatine and choline in caudate nucleus, putamen and occipital cortex of patients with Huntington’s disease, symptomatics and asymptomatics. Subjects and methods. Hydrogen magnetic resonance spectroscopy was performed with a 3 T scanner in 10 Huntington’s disease gene-tested subjects, included in three groups: negative (control), positive sympomatics and positive asymptomatics. Data was quantified with LCModel and analyzed with ANOVA and Fisher tests. Results. Symptomatic patients showed decreased creatine and N-acetylaspartate in the three regions, and decreasedcholine only in putamen (p < 0.05). Choline difference was found between symptomatics and asymptomatics in the caudate nucleus (p < 0.05). Conclusions. Results may reflect neuronal dysfunction and suggest that creatine and choline may serve as markers for Huntington’s disease progression (AU)

[Hydrogen magnetic resonance quantitative spectroscopy at 3 T in symptomatic and asymptomatic Huntington's disease patients]. / Espectroscopia cuantitativa de hidrógeno por resonancia magnética de 3 T en pacientes sintomáticos y asintomáticoscon enfermedad de Huntington.

INTRODUCTION: Huntington's disease is an hereditary autosomic-dominant neurodegenerative disorder, characterized by motor, cognitive and psychiatric symptoms. AIM: To quantify differences in N-acetylaspartate, creatine and choline in caudate nucleus, putamen and occipital cortex of patients with Huntington's disease, symptomatics and asymptomatics. SUBJECTS AND METHODS: Hydrogen magnetic resonance spectroscopy was performed with a 3 T scanner in 10 Huntington's disease gene-tested subjects, included in three groups: negative (control), positive symptomatics and positive asymptomatics. Data was quantified with LCModel and analyzed with ANOVA and Fisher tests. RESULTS: Symptomatic patients showed decreased creatine and N-acetylaspartate in the three regions, and decreased choline only in putamen (p < 0.05). Choline difference was found between symptomatics and asymptomatics in the caudate nucleus (p < 0.05). CONCLUSIONS: Results may reflect neuronal dysfunction and suggest that creatine and choline may serve as markers for Huntington's disease progression.