RESUMEN
α-Synuclein, a protein mostly present in presynaptic terminals, accumulates neuropathologically in Parkinson's disease in a 6-stage sequence and propagates in the nervous system in a prion-like manner through neurons and glia. In stage 3, the substantia nigra are affected, provoking motor symptoms and the amygdaloid complex, leading to different nonmotor symptoms; from here, synucleinopathy spreads to the temporal cortex and beyond. The expected increase in Parkinson's disease incidence accelerates the need for detection biomarkers; however, the heterogeneity of this disease, including pathological aggregates and pathophysiological pathways, poses a challenge in the search for new therapeutic targets and biomarkers. Proteomic analyses are lacking, and the literature regarding synucleinopathy, neural and glial involvement, and volume of the human amygdaloid complex is controversial. Therefore, the present study combines both proteomic and stereological probes. Data-independent acquisition-parallel accumulation of serial fragmentation proteomic analysis revealed a remarkable proteomic impact, especially at the synaptic level in the human amygdaloid complex in Parkinson's disease. Among the 199 differentially expressed proteins, guanine nucleotide-binding protein G(i) subunit alpha-1 (GNAI1), elongation factor 1-alpha 1 (EEF1A1), myelin proteolipid protein (PLP1), neuroplastin (NPTN), 14-3-3 protein eta (YWHAH), gene associated with retinoic and interferon-induced mortality 19 protein (GRIM19), and orosomucoid-2 (ORM2) stand out as potential biomarkers in Parkinson's disease. Stereological analysis, however, did not reveal alterations regarding synucleinopathy, neural or glial populations, or volume changes. To our knowledge, this is the first proteomic study of the human amygdaloid complex in Parkinson's disease, and it identified possible biomarkers of the disease. Lewy pathology could not be sufficient to cause neurodegeneration or alteration of microglial and astroglial populations in the human amygdaloid complex in Parkinson's disease. Nevertheless, damage at the proteomic level is manifest, showing up significant synaptic involvement.
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Enfermedad de Parkinson , Sinucleinopatías , Humanos , Enfermedad de Parkinson/metabolismo , Sinucleinopatías/complicaciones , Proteómica , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Amígdala del Cerebelo/metabolismo , Amígdala del Cerebelo/patología , BiomarcadoresRESUMEN
INTRODUCTION: The entorhinal cortex is among the earliest areas involved in Alzheimer's disease. Volume reduction and neural loss in this area have been widely reported. Human entorhinal cortex atrophy is, in part, due to neural loss, but microglial and/or astroglial involvement in the different layers remains unclear. Additionally, -omic approaches in the human entorhinal cortex are scarce. METHODS: Herein, stereological layer-specific and proteomic analyses were carried out in the human brain. RESULTS: Neurodegeneration, microglial reduction, and astrogliosis have been demonstrated, and proteomic data have revealed relationships with up- (S100A6, PPP1R1B, BAG3, and PRDX6) and downregulated (GSK3B, SYN1, DLG4, and RAB3A) proteins. Namely, clusters of these proteins were related to synaptic, neuroinflammatory, and oxidative stress processes. DISCUSSION: Differential layer involvement among neural and glial populations determined by proteinopathies and identified proteins related to neurodegeneration and astrogliosis could explain how the cortical circuitry facilitates pathological spreading within the medial temporal lobe.
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Enfermedad de Alzheimer , Corteza Entorrinal , Humanos , Corteza Entorrinal/patología , Enfermedad de Alzheimer/patología , Gliosis/patología , Proteómica , Lóbulo Temporal/patología , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Reguladoras de la Apoptosis/metabolismoRESUMEN
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the elderly. Progressive accumulation of insoluble isoforms of amyloid-ß peptide (Aß) and tau protein are the major neuropathologic hallmarks, and the loss of cholinergic pathways underlies cognitive deficits in patients. Recently, glial involvement has gained interest regarding its effect on preservation and impairment of brain integrity. The limbic system, including temporal lobe regions and the olfactory bulb, is particularly affected in the early stages. In the early 1980s, the reduced expression of the somatostatin neuropeptide was described in AD. However, over the last three decades, research on somatostatin in Alzheimer's disease has been scarce in humans. Therefore, the aim of this study was to stereologically quantify the expression of somatostatin in the human hippocampus and olfactory bulb and analyze its spatial distribution with respect to that of Aß and au neuropathologic proteins and astroglia. The results indicate that somatostatin-expressing cells are reduced by 50% in the hippocampus but are preserved in the olfactory bulb. Interestingly, the coexpression of somatostatin with the Aß peptide is very common but not with the tau protein. Finally, the coexpression of somatostatin with astrocytes is rare, although their spatial distribution is very similar. Altogether, we can conclude that somatostatin expression is highly reduced in the human hippocampus, but not the olfactory bulb, and may play a role in Alzheimer's disease pathogenesis.
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Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Astrocitos/metabolismo , Astrocitos/patología , Sistema Límbico/metabolismo , Sistema Límbico/patología , Somatostatina/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Péptidos beta-Amiloides/metabolismo , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Bulbo Olfatorio/metabolismo , Bulbo Olfatorio/patología , Proteínas tau/metabolismoRESUMEN
Alzheimer's disease (AD), the most prevalent neurodegenerative disorder, is characterized by executive dysfunction and memory impairment mediated by the accumulation of extracellular amyloid-ß peptide (Aß) and intracellular hyperphosphorylated tau protein. The hippocampus (HIPP) is essential for memory formation and is involved in early stages of disease. In fact, hippocampal atrophy is used as an early biomarker of neuronal injury and to evaluate disease progression. It is not yet well-understood whether changes in hippocampal volume are due to neuronal or glial loss. The aim of the study was to assess hippocampal atrophy and/or gliosis using unbiased stereological quantification and to obtain hippocampal proteomic profiles related to neurodegeneration and gliosis. Hippocampal volume measurement, stereological quantification of NeuN-, Iba-1- and GFAP-positive cells, and sequential window acquisition of all theoretical mass spectrometry (SWATH-MS) analysis were performed in AD and non-AD cases. Reduced hippocampal volume was identified using the Cavalieri probe, particularly in the CA1 region, where it correlated with neuronal loss and astrogliosis. A total of 102 downregulated and 47 upregulated proteins were identified in the SWATH-MS analysis after restrictive filtering based on an FC > 1.5 and p value < 0.01. The Hsp90 family of chaperones, particularly BAG3 and HSP90AB1, are closely related to astrocytes, indicating a possible role in degrading Aß and tau through chaperone-mediated autophagy.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Enfermedad de Alzheimer/metabolismo , Proteínas Reguladoras de la Apoptosis/metabolismo , Astrocitos/metabolismo , Región CA1 Hipocampal/metabolismo , Gliosis/metabolismo , Proteínas HSP90 de Choque Térmico/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/patología , Astrocitos/patología , Atrofia/metabolismo , Atrofia/patología , Biomarcadores/metabolismo , Progresión de la Enfermedad , Femenino , Gliosis/patología , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Neurodegenerativas/patología , Neuronas/metabolismo , Neuronas/patología , Proteómica/métodosRESUMEN
BACKGROUND: The teaching of human anatomy is often based on practices of cadaver dissection and prosected specimens. However, exposure to human cadavers might be stressful and anxiety-inducing for students. The aim of this study is to explore the degree of satisfaction and anxiety among first-year students in the Medicine, Occupational Therapy, Speech Therapy and Nursing programmes at the Universidad de Castilla-La Mancha (Spain) who are experiencing their first dissection/prosection practice to develop stress coping strategies. METHODS: A total of 204 health sciences students participated in this study. The State-Trait Anxiety Inventory was used to evaluate anxiety. RESULTS: 'State Anxiety' (SA) decreased significantly throughout the course (p < 0.05), from 20.7 ± 19.29 to 13.7 ± 11.65 points. Statistical differences (p < 0.05) in SA were found between the different health sciences, and pre-practice SA was significantly different from post-practice SA. The students with the highest pre-practice SA levels were nursing students (31.8 ± 33.7 points), but medical students had the highest post-practice SA levels (18.4 ± 12.82 points). CONCLUSIONS: Although students were satisfied with dissection practices (96.8% of them recommended that the practices be retained for future courses), the experience can provoke stressful responses that must be addressed using advanced preparation and coping mechanisms, especially among medical and nursing students.
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Anatomía/educación , Ansiedad/psicología , Disección/educación , Educación de Pregrado en Medicina/métodos , Estrés Psicológico/prevención & control , Estudiantes de Medicina/psicología , Adaptación Psicológica , Adulto , Ansiedad/prevención & control , Cadáver , Disección/psicología , Femenino , Humanos , Masculino , España , Estrés Psicológico/psicologíaRESUMEN
BACKGROUND: Dementia is a nonmotor feature of Parkinson's disease, arising around the onset of hippocampal pathology in stage IV of the disease, from where it progress to the isocortex. Differential α-synuclein involvement in hippocampal interneuron populations remains unknown. The objective of this study was to analyze the involvement of α-synuclein in hippocampal interneurons in an α-synucleinopathy mouse model and in the brains of Parkinson's disease patients. METHODS: The distribution of α-synuclein was examined in the dentate gyrus and CA1, CA2, and CA3 fields of the hippocampus in A53T transgenic mice at 16, 30, 43, and 56 weeks and in Parkinson's disease patients at neuropathological stages III, IV, and V. Expression of interneuron markers (mouse: calbindin, calretinin, and somatostatin; human: parvalbumin and somatostatin) were quantified and compared. Coexpression of these markers with α-synuclein was analyzed. RESULTS: In mice, α-synuclein expression was most concentrated in the granular and polymorphic layers of the dentate gyrus and in the CA2 and CA3 fields. Expression significantly increased at 30 and 43 weeks and then significantly decreased at 56 weeks. In human brains, a significantly higher density of α-synuclein was observed in the CA2. The expression of interneuron markers was, in general, not significantly different between control and transgenic animals, except in calbindin and somatostatin at 43 weeks. The α-synuclein protein colocalized with somatostatin and calbindin in the mouse hippocampus and with parvalbumin in the human hippocampus. CONCLUSIONS: The differential α-synucleinopathy of hippocampal interneuron populations may help in the study of mechanisms of protein aggregation and progression relevant to PD and PD dementia. © 2016 International Parkinson and Movement Disorder Society.
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Hipocampo/metabolismo , Interneuronas/metabolismo , Enfermedad de Parkinson/metabolismo , Bancos de Tejidos , alfa-Sinucleína/metabolismo , Animales , Modelos Animales de Enfermedad , Humanos , Ratones , Ratones TransgénicosRESUMEN
Lewy bodies (ubiquitin and α-synuclein aggregates) can be detected in brain areas in a predictable sequence of six neuropathological stages in Parkinson's disease. Brainstem and olfactory structures are involved in stage 1, whereas the substantia nigra and amygdala are involved in stage 3, prior to cortical spreading. Amygdaloid pathology has been suggested to contribute to non-motor symptoms such as olfactory dysfunction and emotional impairment. This work analysed the distribution of α-synuclein at 16, 30, 43 and 56 weeks in the basolateral, central and cortical amygdaloid complexes of A53T transgenic mice. The expression of calbindin, calretinin and somatostatin was compared in control and transgenic animals. Co-localisation of these markers with α-synuclein was performed. Triple labeling of calbindin, somatostatin and α-synuclein was also investigated. Quantification was carried out using an optical dissector, ImageJ software and confocal microscopy. α-Synuclein-positive cells were mainly concentrated in the basolateral and cortical amygdaloid complexes with a non-significant increase over time from 16 to 30-43 weeks and a significant decrease thereafter. The expression of interneuron markers showed a significant decrease with aging in control animals. When comparing these markers between control and transgenic mice, calretinin was moderately decreased, but calbindin and somatostatin were highly reduced, particularly in the cortical amygdaloid complex. α-Synuclein mostly co-localised with calbindin and a number of these cells also co-expressed somatostatin. These data on α-synucleinopathy staging in the amygdala could help to explain non-motor symptoms as well as to understand the progression of Parkinson's disease in the brain.
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Envejecimiento/patología , Amígdala del Cerebelo/patología , Interneuronas/patología , Trastornos Parkinsonianos/patología , alfa-Sinucleína/metabolismo , Envejecimiento/metabolismo , Amígdala del Cerebelo/metabolismo , Animales , Calbindina 2/metabolismo , Calbindinas/metabolismo , Progresión de la Enfermedad , Femenino , Inmunohistoquímica , Interneuronas/metabolismo , Masculino , Ratones Transgénicos , Microscopía Confocal , Trastornos Parkinsonianos/metabolismo , Índice de Severidad de la Enfermedad , Somatostatina/metabolismo , alfa-Sinucleína/genéticaRESUMEN
Alzheimer's disease (AD), the most prevalent neurodegenerative disorder worldwide, is clinically characterized by cognitive deficits. Neuropathologically, AD brains accumulate deposits of amyloid-ß (Aß) and tau proteins. Furthermore, these misfolded proteins can propagate from cell to cell in a prion-like manner and induce native proteins to become pathological. The entorhinal cortex (EC) is among the earliest areas affected by tau accumulation along with volume reduction and neurodegeneration. Neuron-glia interactions have recently come into focus; however, the role of microglia and astroglia in the pathogenesis of AD remains unclear. Proteomic approaches allow the determination of changes in the proteome to better understand the pathology underlying AD. Bioinformatic analysis of proteomic data was performed to compare ECs from AD and non-AD human brain tissue. To validate the proteomic results, western blot, immunofluorescence, and confocal studies were carried out. The findings revealed that the most disturbed signaling pathway was synaptogenesis. Because of their involvement in synapse function, relationship with Aß and tau proteins and interactions in the pathway analysis, three proteins were selected for in-depth study: HSP90AA1, PTK2B, and ANXA2. All these proteins showed colocalization with neurons and/or astroglia and microglia and with pathological Aß and tau proteins. In particular, ANXA2, which is overexpressed in AD, colocalized with amoeboid microglial cells and Aß plaques surrounded by astrocytes. Taken together, the evidence suggests that unbalanced expression of HSP90AA1, PTK2B, and ANXA2 may play a significant role in synaptic homeostasis and Aß pathology through microglial and astroglial cells in the human EC in AD.
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Enfermedad de Alzheimer , Péptidos beta-Amiloides , Anexina A2 , Astrocitos , Corteza Entorrinal , Quinasa 2 de Adhesión Focal , Microglía , Proteómica , Sinapsis , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Humanos , Corteza Entorrinal/metabolismo , Corteza Entorrinal/patología , Astrocitos/metabolismo , Astrocitos/patología , Microglía/metabolismo , Microglía/patología , Proteómica/métodos , Péptidos beta-Amiloides/metabolismo , Anexina A2/metabolismo , Anciano , Sinapsis/metabolismo , Sinapsis/patología , Quinasa 2 de Adhesión Focal/metabolismo , Masculino , Femenino , Anciano de 80 o más Años , Proteínas HSP90 de Choque Térmico/metabolismo , Homeostasis/fisiología , Proteínas tau/metabolismoRESUMEN
Alzheimer's disease (AD) is characterized by the accumulation of pathological amyloid-ß (Aß) and Tau proteins. According to the prion-like hypothesis, both proteins can seed and disseminate through brain regions through neural connections and glial cells. The amygdaloid complex (AC) is involved early in the disease, and its widespread connections with other brain regions indicate that it is a hub for propagating pathology. To characterize changes in the AC as well as the involvement of neuronal and glial cells in AD, a combined stereological and proteomic analysis was performed in non-Alzheimer's disease and AD human samples. The synaptic alterations identified by proteomic data analysis could be related to the volume reduction observed in AD by the Cavalieri probe without neuronal loss. The pathological markers appeared in a gradient pattern with the medial region (cortical nucleus, Co) being more affected than lateral regions, suggesting the relevance of connections in the distribution of the pathology among different brain regions. Generalized astrogliosis was observed in every AC nucleus, likely related to deposits of pathological proteins. Astrocytes might mediate phagocytic microglial activation, whereas microglia might play a dual role since protective and toxic phenotypes have been described. These results highlight the potential participation of the amygdala in the disease spreading from/to olfactory areas, the temporal lobe and beyond. Proteomic data are available via ProteomeXchange with identifier PXD038322.
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Enfermedad de Alzheimer , Proteómica , Humanos , Enfermedad de Alzheimer/patología , Proteínas tau/metabolismo , Péptidos beta-Amiloides/metabolismo , Encéfalo/patología , Microglía/patología , Amígdala del Cerebelo/metabolismo , Amígdala del Cerebelo/patologíaRESUMEN
Despite its robust proteopathic nature, the spatiotemporal signature of disrupted protein modules in sporadic Alzheimer's disease (AD) brains remains poorly understood. This considered oxidative stress contributes to AD progression and early intervention with coenzyme Q10 or its reduced form, ubiquinol, delays the progression of the disease. Using MALDI-MSI and functional bioinformatic analysis, we have developed a protocol to express how deregulated protein modules arise from hippocampus and cortex in the AD mice model 3xTG-AD in an age-dependent manner. This strategy allowed us to identify which modules can be efficiently restored to a non-pathological condition by early intervention with ubiquinol. Indeed, an early deregulation of proteostasis-related protein modules, oxidative stress and metabolism has been observed in the hippocampus of 6-month mice (early AD) and the mirrored in cortical regions of 12-month mice (middle/late AD). This observation has been validated by IHC using mouse and human brain sections, suggesting that these protein modules are also affected in humans. The emergence of disrupted protein modules with AD signature can be prevented by early dietary intervention with ubiquinol in the 3xTG-AD mice model.
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Hyposmia is one of the prodromal symptoms of Parkinson's disease (PD) and a red flag in clinical diagnosis. Neuropathologically, this sign correlates with α-synuclein involvement in the anterior olfactory nucleus (AON). Neurodegeneration, microgliosis, and astrogliosis in AON are poorly studied, and bulbar AON is the focus of these studies with contradictory results. Additionally, male sex is a risk marker for developing PD, but sexual dimorphism of neural and glial populations in the AON has rarely been considered. The aim of this study was to analyze the density of NeuN, Iba-1, GFAP, and Lewy bodies (LBs), as well as the relationship of these cell type markers with pathology along the rostrocaudal axis of the AON (bulbar, retrobulbar, cortical anterior, and posterior divisions). Cavalieri, optical fractionator, and area fraction fractionator stereological approaches were used for the volume, cell populations and LBs densities, area fraction, and percentage of overlap. Iba-1 and α-syn intensities were measured using ImageJ. In non-PD (NPD) cases, the volume was lower in the AON at the extremes of the rostrocaudal axis than in the intermediate divisions. Cortical anterior AON volume decreased in PD compared with NPD cases. NeuN density decreased rostrocaudally in AON portions in NPD and PD cases. This occurred similarly in Iba-1 but only in PD samples. Iba-1 intensity significantly increased in bulbar AON between PD and NPD. No changes were found in astrocytes. Eight percent of NeuN, 0.1% of Iba-1, and 0.1% of GFAP areas overlapped with LBs area along the AON portions. The data indicate that bulbar AON, which is the most rostral portion in this axis, could play a major role in the pathology. This could be related to the larger area occupied by LBs in these divisions.
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Background: Part of the basic teaching of human anatomy are prosection sessions with a human corpse, which may generate stress or anxiety among students. The objective of this work was to study how, through the visualization technique (a coping technique), these levels could be reduced before starting prosection classes. Methods: A cross-sectional pilot study was conducted involving first-year students who had never participated in screening sessions. Prior to the visit, occupational therapy students underwent a viewing session (visualization technique). On the day of the visit, before and after the screening session, an anonymous questionnaire was distributed to find out about aspects of the students' experiences, such as their feelings and perceptions. The State−Trait Anxiety Inventory was used to assess anxiety. Results: The baseline levels of anxiety measured remained stable (from 18.5 to 18.2 points), with no differences being found (p > 0.05). The levels of emotional anxiety measured fell from 15.2 to 12.6 points (p < 0.05). Before starting the class, there were six students (17.1%) with anxiety criteria, and this figure was doubled at the end of the session (33.3%) (p < 0.05). Conclusions: Sessions in a dissection room can cause stressful experiences and change the emotional balances of some students. The results obtained and published here showed no significant differences after the visualization technique. We found that the students believed that the prosection sessions were very useful for teaching anatomy.
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An in-depth understanding of the anatomy discipline is essential for the work of healthcare professionals. In recent decades, the content and time of teaching anatomy have decreased in all health science degrees. The aim of this study was to look for alternatives for compensating the reduction of the teaching of anatomy by supplementing students with a practical training course and to know evaluations of the course given by students enrolled in the degree in Speech Therapy and its impact on their academic results. All students (100%) positively evaluated having acquired skills and attitudes for their future professional life. The majority of the students (95.8%) believed that their knowledge was acceptable; 97.2% of the students thought they would have the possibility to apply their acquired anatomical knowledge as professionals; 98.5% were satisfied with the voluntary course; and finally, the percentage of students that passed the "Anatomophysiology of language and voice organs" course increased from previous academic years. Optional (theoretical/practical) undergraduate courses can be used in parallel to overcome the devaluation of anatomical studies in new curricula. The optional undergraduate anatomy course in the Speech Therapy program has been positively evaluated because it stimulated students' motivation and appealed to their interest in anatomy. Students considered that these courses would help them in their training and they could put what they had learned into practice in their future professions. However, very little evidence for the impact of optional practical courses exists, yet it could be an efficient method to increase anatomical knowledge.
Asunto(s)
Anatomía , Educación de Pregrado en Medicina , Estudiantes de Medicina , Anatomía/educación , Curriculum , Humanos , LogopediaRESUMEN
Hyposmia is prodromal, and male sex is a risk marker for an enhanced likelihood ratio of Parkinson's disease. The literature regarding olfactory bulb volume reduction is controversial, although the olfactory bulb has been largely reported as an early and preferential site for α-synucleinopathy. These pathological deposits have been correlated with neural loss in Nissl-stained material. However, microgliosis has rarely been studied, and astrogliosis has been virtually neglected. In the present report, α-synucleinopathy (α-synuclein), neurodegeneration (Neu-N), astrogliosis (GFAP), and microgliosis (Iba-1) were quantified, using specific markers and stereological methods. Disease, sex, age, disease duration, and post-mortem interval were considered variables for statistical analysis. No volumetric changes have been identified regarding disease or sex. α-Synucleinopathy was present throughout the OB, mainly concentrated on anterior olfactory nucleus. Neurodegeneration (reduction in Neu-N-positive cells) was statistically significant in the diseased group. Astrogliosis (increased GFAP labeling) and microgliosis (increased Iba-1 labeling) were significantly enhanced in the Parkinson's disease group. When analyzed per sex, neurodegeneration and microgliosis differences are only present in men. These data constitute the demonstration of sex differences in neurodegeneration using specific neural markers, enhanced astrogliosis and increased microgliosis, also linked to male sex, in the human olfactory bulb in Parkinson's disease.
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BACKGROUND: Parkinson's disease (PD) is a prevalent neurodegenerative disease that is pathologically described as a six-stage α-synucleinopathy. In stage 4, α-synuclein reaches the hippocampus, inducing cognitive deficits, from which it progresses to the isocortex, leading to dementia. Among hippocampal fields, cornu ammonis 2 is particularly affected by this α-synucleinopathy and critical for cognitive decline. Volumetric studies using magnetic resonance imaging have produced controversial results, with only some reporting volume loss, whereas stereological data obtained using nonspecific markers do not reveal volume changes, neural or glial loss. Proteomic analysis has not been carried out in the hippocampus of patients with PD. OBJECTIVE: This study aims to explain hippocampal changes in patients with PD at the cellular and proteomic levels. METHODS: α-Synuclein inclusions, volume and neural (NeuN), microglial (Iba-1) and astroglial (GFAP) populations were stereologically analyzed. SWATH-MS quantitative proteomic analysis was also conducted. RESULTS: Area fraction fractionator probe revealed a higher area fraction α-synucleinopathy in cornu ammonis 2. No volume change, neurodegeneration, microgliosis or astrogliosis was detected. Proteomic analysis identified 1,634 proteins, of which 83 were particularly useful for defining differences among PD and non-PD groups. Among them, upregulated (PHYIP, CTND2, AHSA1 and SNTA1) and downregulated (TM163, REEP2 and CSKI1) proteins were related to synaptic structures in the diseased hippocampus. CONCLUSION: The distribution of α-synuclein in the hippocampus is not associated with volumetric, neural or glial changes. Proteomic analysis, however, reveals a series of changes in proteins associated with synaptic structures, suggesting that hippocampal changes occur at the synapse level during PD.
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Hipocampo , Enfermedad de Parkinson , Hipocampo/metabolismo , Humanos , Enfermedad de Parkinson/metabolismo , Proteómica , Sinucleinopatías , alfa-Sinucleína/metabolismoRESUMEN
Alzheimer's and Parkinson's diseases are the most prevalent neurodegenerative disorders in aging. Hyposmia has been described as an early symptom that can precede cognitive and motor deficits by decades. Certain regions within the olfactory system, such as the anterior olfactory nucleus, display the neuropathological markers tau and amyloid-ß or α-synuclein from the earliest stages of disease progression in a preferential manner. Specific neuronal subpopulations, namely those expressing somatostatin (SST), are preferentially affected throughout the olfactory and limbic systems. SST is a neuropeptide present in a subpopulation of GABAergic interneurons throughout the brain and its main function is to inhibit principal neurons and/or other interneurons. It has been reported that SST expression is reduced by 50% in Alzheimer's disease and that it is related to the formation of Aß oligomers. The mechanisms underlying the preferential vulnerability of SST-expressing neurons in Alzheimer's disease (and, to a minor extent, in Parkinson's disease) are not known but analysis of the available data could shed light on their etiology. This short review aims to update the knowledge of functional features of somatostatin within the olfactory system and its role in olfactory deficits during neurodegeneration.
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Dissection and prosection practices using human cadavers are a key component of macroscopic anatomy education in different Health Sciences university degrees. However, first-hand interaction with cadavers can be distressing for students, generating anxiety on a number of levels. This study aims to shed light on the reactions, fears and different states of anxiety experienced by nursing students in to a single anatomy room experience over a five-hour period, and examined reactions pre and post same. A descriptive study of these students was designed in order to understand their feelings and emotions, based on the distribution of anonymous "ad hoc" questionnaires before and after the practices. Also, State-Trait Anxiety Inventory (STAI) questionnaires were administered in order to assess their anxiety levels: Trait Anxiety (TA), which measures basal anxiety levels, and State Anxiety (SA), which measures individual emotional responses during a specific event (in this case, the prosection practice). The results of this study indicate that basal anxiety levels, measured as TA, remained stable and unchanged during the practice (p > 0.05). SA or emotional anxiety levels, on the other hand, dropped from 21.3 to 17.8 points (p < 0.05). Before the start of the practical exercise, 17.6% of the students admitted experiencing some kind of anxiety. Afterwards, however, 90.2% of the students said they would recommend these practices. They considered that prosection practices very useful for their education and recommended that they be retained for future courses. However, our study also showed the relevance of using coping mechanisms before the first contact with the dissecting room, especially for those students who did not feel emotionally prepared for it beforehand.
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Ansiedad/etiología , Disección/psicología , Estudiantes de Enfermería/psicología , Adaptación Psicológica , Adolescente , Ansiedad/psicología , Disección/efectos adversos , Disección/métodos , Bachillerato en Enfermería/métodos , Bachillerato en Enfermería/normas , Bachillerato en Enfermería/estadística & datos numéricos , Femenino , Humanos , Masculino , Psicometría/instrumentación , Psicometría/métodos , España , Estudiantes de Enfermería/estadística & datos numéricos , Encuestas y Cuestionarios , Universidades/organización & administración , Universidades/estadística & datos numéricos , Adulto JovenRESUMEN
Alzheimer's and Parkinson's diseases are the most prevalent neurodegenerative disorders. Their etiologies are idiopathic, and treatments are symptomatic and orientated towards cognitive or motor deficits. Neuropathologically, both are proteinopathies with pathological aggregates (plaques of amyloid-ß peptide and neurofibrillary tangles of tau protein in Alzheimer's disease, and Lewy bodies mostly composed of α-synuclein in Parkinson's disease). These deposits appear in the nervous system in a predictable and accumulative sequence with six neuropathological stages. Both disorders present a long prodromal period, characterized by preclinical signs including hyposmia. Interestingly, the olfactory system, particularly the anterior olfactory nucleus, is initially and preferentially affected by the pathology. Cerebral atrophy revealed by magnetic resonance imaging must be complemented by histological analyses to ascertain whether neuronal and/or glial loss or neuropil remodeling are responsible for volumetric changes. It has been proposed that these proteinopathies could act in a prion-like manner in which a misfolded protein would be able to force native proteins into pathogenic folding (seeding), which then propagates through neurons and glia (spreading). Existing data have been examined to establish why some neuronal populations are vulnerable while others are resistant to pathology and to what extent glia prevent and/or facilitate proteinopathy spreading. Connectomic approaches reveal a number of hubs in the olfactory system (anterior olfactory nucleus, olfactory entorhinal cortex and cortical amygdala) that are key interconnectors with the main hubs (the entorhinal-hippocampal-cortical and amygdala-dorsal motor vagal nucleus) of network dysfunction in Alzheimer's and Parkinson's diseases.
Asunto(s)
Enfermedad de Alzheimer/diagnóstico por imagen , Vías Olfatorias/diagnóstico por imagen , Enfermedad de Parkinson/diagnóstico por imagen , Olfato/fisiología , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/fisiopatología , Humanos , Trastornos del Olfato/complicaciones , Trastornos del Olfato/fisiopatología , Bulbo Olfatorio/diagnóstico por imagen , Bulbo Olfatorio/fisiopatología , Vías Olfatorias/fisiopatología , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/fisiopatologíaRESUMEN
Parkinson's disease is characterized by a proteinopathy that includes aggregates of α-synuclein. A recent hypothesis proposes a prion-like spreading mechanism for this α-synucleinopathy. Early neuropathological deposits occur, among others, in the anterior olfactory nucleus (AON). This study investigates the anterograde and/or retrograde transmissibility of exogenous α-synuclein inoculated in the right AON of the A53T model of Parkinson's disease and wild-type mice as well as neuronal and glial involvement. Seven experimental groups were established: wild-type injected with tracers; A53T mice injected with either α-synuclein or saline 2 months beforehand; wild-type injected with either α-synuclein or saline 2 months beforehand; and wild-type injected with either α-synuclein or saline 4 months beforehand. Weight and behavioral changes were analyzed. Immunohistochemistry against α-synuclein, NeuN, Iba-1 and GFAP was performed. Volume and marker distributions in the olfactory bulb (OB), AON and piriform cortex were analyzed using unbiased stereology. The behavioral analyses reveal higher levels of hyperactivity in transgenic as compared to wild-type mice. Tract-tracing experiments show that the main contralateral afferent projections to the dorsal AON come from the AON and secondarily from the OB. In saline-injected transgenic animals, α-synuclein expression in the OB and the AON is higher in the left hemisphere than in the right hemisphere, which could be due to basal interhemispheric differences. α-synuclein injection could provoke a significant increase in the left hemisphere of the transgenic mice's OB, compared to saline-injected animals. Neuronal loss was observed in saline-injected transgenic mice relative to the saline-injected wild-type group. There were no overall differences in neuron number following injection of α-synuclein into either wild-type or transgenic mice, however some neuron loss was apparent in specific regions of α-synuclein injected wild-types. Microglia labeling appeared to be correlated with surgery-induced inflammation. Astroglial labeling was higher in transgenic animals, which could be due to endogenous α-synucleinopathy. This study suggests α-synucleinopathy induction, via retrograde and contralateral projections, within the olfactory system of transgenic animals.
Asunto(s)
Corteza Olfatoria/metabolismo , Enfermedad de Parkinson/metabolismo , alfa-Sinucleína/metabolismo , Animales , Astrocitos/metabolismo , Modelos Animales de Enfermedad , Encefalitis/complicaciones , Encefalitis/metabolismo , Masculino , Ratones Transgénicos , Microglía/metabolismo , Neuronas/metabolismo , Neuronas/patología , Corteza Olfatoria/patología , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/patologíaRESUMEN
Practical training in the dissection of human cadavers is a fundamental and traditional component of human anatomy education in medical schools. This practice, however, can be stressful for students and can generate a certain amount of anxiety. The aim of this study is to explore the attitudes, reactions, and anxiety levels of first-year medical students when working in the dissecting room, over a period of one year, and to relate these anxiety levels to the results of our educational program. This is a before and after descriptive study of students at the University of Castilla-La-Mancha. Questionnaires were distributed among them before and after their dissection practices in order to understand their feelings and emotions and their satisfaction about this activity. State-Trait Anxiety Inventory questionnaires were used to assess the students' 'state anxiety' (SA), which dropped significantly from 49.1% to 14% by the end of their first year. Female students started with higher levels of SA than their male counterparts but by the end of the year these had dropped to similar levels. Anxiety and fearful thoughts tended to drop (P > 0.05). In contrast, uncertainty levels showed significant changes, falling from 44.4% to 12.3%. Nonetheless, 100% of students would go through the experience again. Indeed, 98.2% considered that dissection practices were useful in reinforcing the theoretical aspects of their education, and 80.7% believed that dissecting was more useful than theoretical models. Although students were satisfied with dissection practices the experience cause stressful responses.