Memantine protects cholinergic and glutamatergic septal neurons from Aβ1-40-induced toxicity

The medial septal region (medial septum and diagonal band of Broca, MS/DB) controls hippocampal excitability and synaptic plasticity. MS/DB cholinergic neurons degenerate early in Alzheimer’s disease (AD). The presence of MS/DB glutamatergic neurons that project to the hippocampus and are vulnerable to Aβ suggests that excitotoxicity plays a role in AD septal degeneration and hippocampal dysfunction. To demonstrate the presence of excitotoxicity in Aβinduced septal damage, we compared rats injected with Aβ1–40 into the MS/DB with animals treated with memantine prior, during and after Aβ1–40 injections. Controls were injected with phosphate buffered saline (PBS). MS/DB cholinergic, glutamatergic and GABAergic neurons were immunochemically identified. The number of MS/DB neurons was estimated using stereology. Our results show that memantine blocks Aβ1–40-induced septal damage and suggest that excitotoxicity plays a role in basal forebrain neurodegeneration

Memantine protects cholinergic and glutamatergic septal neurons from Aβ1-40-induced toxicity

The medial septal region (medial septum and diagonal band of Broca, MS/DB) controls hippocampal excitability and synaptic plasticity. MS/DB cholinergic neurons degenerate early in Alzheimer\u27s disease (AD). The presence of MS/DB glutamatergic neurons that project to the hippocampus and are vulnerable to Aβ suggests that excitotoxicity plays a role in AD septal degeneration and hippocampal dysfunction. To demonstrate the presence of excitotoxicity in Aβ-induced septal damage, we compared rats injected with Aβ1-40 into the MS/DB with animals treated with memantine prior, during and after Aβ1-40 injections. Controls were injected with phosphate buffered saline (PBS). MS/DB cholinergic, glutamatergic and GABAergic neurons were immunochemically identified. The number of MS/DB neurons was estimated using stereology. Our results show that memantine blocks Aβ1-40-induced septal damage and suggest that excitotoxicity plays a role in basal forebrain neurodegeneration

Electrophysiological and morphological heterogeneity of slow firing neurons in medial septal/diagonal band complex as revealed by cluster analysis

Slow firing septal neurons modulate hippocampal and neocortical functions. Electrophysiologically, it is unclear whether slow firing neurons belong to a homogeneous neuronal population. To address this issue, whole-cell patch recordings and neuronal reconstructions were performed on rat brain slices containing the medial septum/diagonal band complex (MS/DB). Slow firing neurons were identified by their low firing rate at threshold (\u3c 5Hz) and lack of time-dependent inward rectification (Ih). Unsupervised cluster analysis was used to investigate whether slow firing neurons could be further classified into different subtypes. The parameters used for the cluster analysis included latency for first spike, slow afterhyperpolarizing potential, maximal frequency and action potential (AP) decay slope. Neurons were grouped into three major subtypes. The majority of neurons (55%) were grouped as cluster I. Cluster II (17% of neurons) exhibited longer latency for generation of the first action potential (246.5±20.1 ms). Cluster III (28% of neurons) exhibited higher maximal firing frequency (25.3±1.7 Hz) when compared to cluster I (12.3±0.9 Hz) and cluster II (11.8±1.1 Hz) neurons. Additionally, cluster III neurons exhibited faster action potentials at suprathreshold. Interestingly, cluster II neurons were frequently located in the medial septum whereas neurons in cluster I and III appeared scattered throughout all MS/DB regions. Sholl’s analysis revealed a more complex dendritic arborization in cluster III neurons. Cluster I and II neurons exhibited characteristics of “true” slow firing neurons whereas cluster III neurons exhibited higher frequency firing patterns. Several neurons were labeled with a cholinergic marker, Cy3-conjugated 192 IgG (p75NTR), and cholinergic neurons were found to be distributed among the three clusters. Our findings indicate that slow firing medial septal neurons are heterogeneous and that soma location is an important determinant of their electrophysiological properties. Thus, slow firing neurons from different septal regions have distinct functional properties, most likely related to their diverse connectivity

Medial septal beta-amyloid 1-40 injections alter septo-hippocampal anatomy and function

Degeneration of septal neurons in Alzheimer’s disease (AD) results in abnormal information processing at cortical circuits and consequent brain dysfunction. The septum modulates the activity of hippocampal and cortical circuits and is crucial to the initiation and occurrence of oscillatory activities such as the hippocampal theta rhythm. Previous studies suggest that amyloid β peptide (Aβ) accumulation may trigger degeneration in AD. This study evaluates the effects of single injections of Aβ 1–40 into the medial septum. Immunohistochemistry revealed a decrease in septal cholinergic (57%) and glutamatergic (53%) neurons in Aβ 1–40 treated tissue. Additionally, glutamatergic terminals were significantly less in Aβ treated tissue. In contrast, septal GABAergic neurons were spared. Unitary recordings from septal neurons and hippocampal field potentials revealed an approximately 50% increase in firing rates of slow firing septal neurons during theta rhythm and large irregular amplitude (LIA) hippocampal activities and a significantly reduced hippocampal theta rhythm power (49%) in Aβ 1–40 treated tissue. Aβ also markedly reduced the proportion of slow firing septal neurons correlated to the hippocampal theta rhythm by 96%. These results confirm that Aβ alters the anatomy and physiology of the medial septum contributing to septohippocampal dysfunction. The Aβ induced injury of septal cholinergic and glutamatergic networks may contribute to an altered hippocampal theta rhythm which may underlie the memory loss typically observed in AD patients

Los grupos neuronales septales colinérgicos, gabaérgicos y glutamatérgicos y su proyección a hipocampo

Tesis Univ. Granada. Departamento de Bioquímica y Biología Molecular III e Inmunología. Leída el 12 de mayo de 200

El razonamiento clínico desde el ciclo básico, una opción de integración en las ciencias médicas

Background: the clinical reasoning facilitates the integration of knowledge in the formation of health professionals to have an adequate performance in the future profession. Objective: to analyze the general opinion of the students about the inclusion of clinical cases in the Physiology subject to propitiate a clinical reasoning through the biomedical basic sciences. Methods: a descriptive cross-sectional study was carried out in Tamaulipas Autonomous University. The universe comprised the students who were in the third semester of the career from January to May 2013. 60 students who were studying the Physiology subject in this period were included in a non-random consecutive sampling. Theoretical methods were used: Analysis-Synthesis, induction-deduction. Empirical methods: a questionnaire was applied to the students. Results: the students gave satisfactory opinions about the inclusion and discussion of clinical cases in the basic area of the Medicine career. Most of the students stated that the application of the clinical reasoning to the basic knowledge of the career benefits the teaching- learning process. The students regarded as very important the role of the tutors Conclusions: the inclusion of clinical cases in the subjects of the basic sciences allows to achieve the integration of its contents with the clinical sciences, since early stages of the career, it provides advantages to set the bases for a more effective transference and a better development of the clinical reasoning.Fundamento: el razonamiento clínico propicia la integración de conocimientos en la formación del profesional de la salud para el desempeño adecuado de su futura labor. Objetivo: analizar la opinión general de los estudiantes acerca de la inserción de casos clínicos en la asignatura Fisiología, para propiciar el desarrollo del razonamiento clínico desde las ciencias básicas biomédicas. Métodos: se realizó un estudio descriptivo transversal en la Facultad de Medicina de la Universidad Autónoma de Tamaulipas. El universo estuvo constituido por los estudiantes del tercer semestre de la carrera durante el período de enero a mayo de 2013. Se seleccionó una muestra de 60 que cursaban la asignatura de Fisiología en ese período, mediante un muestro no probabilístico consecutivo. Se utilizaron métodos teóricos: análisis-síntesis, inductivo-deductivo, y empírico: cuestionario a estudiantes. Resultados: se constató una opinión satisfactoria por parte de los estudiantes, sobre la discusión de casos clínicos en los contenidos del área básica de la carrera de Medicina. La mayoría de ellos determinó que la aplicación del razonamiento clínico en los conocimientos básicos de la carrera, beneficia el proceso enseñanza aprendizaje. Los estudiantes consideraron importante el papel del tutor en la metodología utilizada. Conclusiones: la inserción de casos clínicos en las asignaturas de las ciencias básicas para lograr la integración de sus contenidos con las ciencias clínicas, desde etapas tempranas de la carrera, ofrece ventajas para sentar las bases de una transferencia más efectiva y un mejor desarrollo del razonamiento clínico

El razonamiento clínico desde el ciclo básico, una opción de integración en las ciencias médicas

Fundamento: el razonamiento clínico propicia la integración de conocimientos en la formación del profesional de la salud para el desempeño adecuado de su futura labor. Objetivo: analizar la opinión general de los estudiantes acerca de la inserción de casos clínicos en la asignatura Fisiología, para propiciar el desarrollo del razonamiento clínico desde las ciencias básicas biomédicas. Métodos: se realizó un estudio descriptivo transversal en la Facultad de Medicina de la Universidad Autónoma de Tamaulipas. El universo estuvo constituido por los estudiantes del tercer semestre de la carrera durante el período de enero a mayo de 2013. Se seleccionó una muestra de 60 que cursaban la asignatura de Fisiología en ese período, mediante un muestro no probabilístico consecutivo. Se utilizaron métodos teóricos: análisis-síntesis, inductivo-deductivo, y empírico: cuestionario a estudiantes. Resultados: se constató una opinión satisfactoria por parte de los estudiantes, sobre la discusión de casos clínicos en los contenidos del área básica de la carrera de Medicina. La mayoría de ellos determinó que la aplicación del razonamiento clínico en los conocimientos básicos de la carrera, beneficia el proceso enseñanza aprendizaje. Los estudiantes consideraron importante el papel del tutor en la metodología utilizada. Conclusiones: la inserción de casos clínicos en las asignaturas de las ciencias básicas para lograr la integración de sus contenidos con las ciencias clínicas, desde etapas tempranas de la carrera, ofrece ventajas para sentar las bases de una transferencia más efectiva y un mejor desarrollo del razonamiento clínico. - Background: the clinical reasoning facilitates the integration of knowledge in the formation of health professionals to have an adequate performance in the future profession. Objective: to analyze the general opinion of the students about the inclusion of clinical cases in the Physiology subject to propitiate a clinical reasoning through the biomedical basic sciences. Methods: a descriptive cross-sectional study was carried out in Tamaulipas Autonomous University. The universe comprised the students who were in the third semester of the career from January to May 2013. 60 students who were studying the Physiology subject in this period were included in a non-random consecutive sampling. Theoretical methods were used: Analysis-Synthesis, induction-deduction. Empirical methods: a questionnaire was applied to the students. Results: the students gave satisfactory opinions about the inclusion and discussion of clinical cases in the basic area of the Medicine career. Most of the students stated that the application of the clinical reasoning to the basic knowledge of the career benefits the teaching- learning process. The students regarded as very important the role of the tutors. Conclusions: the inclusion of clinical cases in the subjects of the basic sciences allows to achieve the integration of its contents with the clinical sciences, since early stages of the career, it provides advantages to set the bases for a more effective transference and a better development of the clinical reasoning

La diabetes y la alimentación determinantes en la progresión de aterosclerosis

El propósito de esta revisión es analizar la progresión bioquímica de la placa aterosclerótica y la relación que presenta con la diabetes y la alimentación. Se exponen las evidencias científicas de pacientes con diabetes, que a diferencia de pacientes no diabéticos presentan niveles más elevados de algunos ácidos grasos en la placa de ateroma (como el palmítico, linoleico y oleico), elevada incidencia de trombosis coronaria relacionada con el incremento en el tama˜no de la base necrótica y la disminución del tama˜no de la capa fibrosa de los ateromas. Entre ambos grupos de pacientes se expone la diferencia en el perfil de lípidos de la placa aterosclerótica, así como los cambios celulares involucrados en la formación de la misma y la influencia de la alimentación sobre su desarrollo. - The purpose of this review is to analyze the biochemical progression of atherosclerotic plaque and its association with diet and diabetes. This study shows the scientific evidence of demonstrating that diabetic patients present high levels of fatty acids like palmitic acid and linoleic acid in their atheroma plaques in comparison with non-diabetic patients. This study also establishes how patients with diabetes mellitus have a higher prevalence of atherosclerotic heart diseases in the form of Coronary Thrombosis and have different anatomopathological appearance like higher necrotic core and thin fibrotic layer than the general population. Furthermore this review describes the different anatomopathological appearance and cellular changes involved in the formation of these plaques and how diet can affect the development of these plaques