Histological and Memory Alterations in an Innovative Alzheimer's Disease Animal Model by Vanadium Pentoxide Inhalation.

Background: Previous work from our group has shown that chronic exposure to Vanadium pentoxide (V2O5) causes cytoskeletal alterations suggesting that V2O5 can interact with cytoskeletal proteins through polymerization and tyrosine phosphatases inhibition, causing Alzheimer's disease (AD)-like hippocampal cell death. Objective: This work aims to characterize an innovative AD experimental model through chronic V2O5 inhalation, analyzing the spatial memory alterations and the presence of neurofibrillary tangles (NFTs), amyloid-ß (Aß) senile plaques, cerebral amyloid angiopathy, and dendritic spine loss in AD-related brain structures. Methods: 20 male Wistar rats were divided into control (deionized water) and experimental (0.02 M V2O5 1 h, 3/week for 6 months) groups (n = 10). The T-maze test was used to assess spatial memory once a month. After 6 months, histological alterations of the frontal and entorhinal cortices, CA1, subiculum, and amygdala were analyzed by performing Congo red, Bielschowsky, and Golgi impregnation. Results: Cognitive results in the T-maze showed memory impairment from the third month of V2O5 inhalation. We also noted NFTs, Aß plaque accumulation in the vascular endothelium and pyramidal neurons, dendritic spine, and neuronal loss in all the analyzed structures, CA1 being the most affected. Conclusions: This model characterizes neurodegenerative changes specific to AD. Our model is compatible with Braak AD stage IV, which represents a moment where it is feasible to propose therapies that have a positive impact on stopping neuronal damage.

Diferencias en la atención sostenida en jóvenes universitarios con distintos niveles de uso de smartphone / Differences in sustained attention in young university students with different levels of smartphone use

Resumen El uso constante de los dispositivos móviles está generando nuevos fenómenos de comportamiento. En años recientes, se ha puesto énfasis en los cambios cognitivos que se podrían generar en los jóvenes que hacen uso excesivo de estos dispositivos. El objetivo del trabajo fue conocer las diferencias en la atención sostenida en jóvenes universitarios asociadas a distintos niveles de uso del teléfono inteligente. Se obtuvo una muestra de 94 adultos, 34 hombres y 60 mujeres de 18 a 23 años (M = 19.34, DE = 1.09) alumnos de la escuela superior de Actopan, Hidalgo-México. Se aplicó la Escala de Dependencia y Adicción al Smartphone EDAS (Aranda-López et al., 2017) y una prueba computarizada de ejecución continua (CPT) Test of Atenttional Vigilance (TOAV; Mueller y Pipper, 2014). Se realizó un ANOVA de una vía, en el que la variable independiente fue el nivel de uso del teléfono inteligente (sin dependencia, dependencia y adicción) y la variable dependiente fueron las puntuaciones obtenidas en el TOAV. Se observó que existen diferencias significativas a nivel estadístico en lo relativo a errores de omisión de la segunda mitad de la prueba (p = .005); las diferencias fueron entre los grupos de sin dependencia-dependencia (p = .010) y sin dependencia-adicción (p = .024). Acorde a los hallazgos del presente estudio, existen diferencias en el proceso de atención sostenida entre usuarios con diferentes niveles de uso del teléfono inteligente; los estudiantes con niveles de dependencia y adicción enfrentan dificultades en la atención sostenida cuando la tarea se prolonga y aumenta la demanda cognitiva.

Abstract The constant use of mobile devices changed our lives dramatically during the past years and its usage increased over the years. Smartphone use is associated with isolation and interpersonal problems; its overuse can cause cognitive problems too (Matar Boumosleh & Jaalouk, 2017). Cognitive problems associated with smartphones in young people are reduction of sustained attention and working memory. Findings have been reported in which younger populations show deterioration in different components of care, highlighting the difficulty of walking and using the smartphone at the same time (Prupetkaew et al., 2019). It has been reported that the impulsivity associated with use of smartphone in silent mode interferes in memory tests unlike when it is in off mode in young populations (Canale et al., 2019). It is necessary to evaluate the effects of using a smartphone on young people because it is a population that uses it constantly to develop in work, academic, sports, and even socializing activities. The aim of this paper was to find out the differences in sustained attention in young university students with different levels of smartphone use. A sample of 94 adults, 34 men and 60 women between the ages of 18 and 23 (M = 19.34, SD = 1.09), who were students of the higher school of Actopan, Hidalgo-Mexico. The EDAS -Smartphone Dependency and Addiction Scale- was applied (Aranda-López et al., 2017). For the evaluation of attention, a Computerized Continuous Running Test (CPT), Test of Attentional Vigilance (TOAV) was applied using the Psychology Experimental Building Language PEBL-2 platform (Mueller & Pipper, 2014). The inclusion criteria were that the participants were between 18-23 years old, right-handed, with normal and/or corrected vision. They were excluded from the investigation if they had a history of psychiatric and/or neurological diseases, learning difficulties, chronic alcohol and/or drug use. A one-way ANOVA was performed, where the independent variable was the level of smartphone use (no dependence, dependence and addiction) and the dependent variable was the scores obtained in the TOAV. It was observed that there are statistically significant differences in the errors of omission of the second half of the test (p = .05), the differences were found between the groups of no dependence-dependence (p =.10) and without dependence-addiction (p = .24). The results showed that there are differences in the execution of a neuropsychological task, regarding the omission errors of the second part of the test. These differences could suggest that the level of sustained attention is diminished in the participants of the dependency and addiction group at the end of the task. On the other hand, it is also concluded that students with levels of dependence and smartphone addiction face attention difficulties when the task is longer and cognitive demand increases. This type of data must be analyzed taking into consideration variables such as sex, socioeconomic level, age, profile of use, quality of sleep, level of physical activity, among others.

The presence of perforated synapses in the striatum after dopamine depletion, is this a sign of maladaptive brain plasticity?

Synaptic plasticity is the process by which long-lasting changes take place at synaptic connections. The phenomenon itself is complex and can involve many levels of organization. Some authors separate forms into adaptations that have positive or negative consequences for the individual. It has been hypothesized that an increase in the number of synapses may represent a structural basis for the enduring expression of synaptic plasticity during some events that involve memory and learning; also, it has been suggested that perforated synapses increase in number after some diseases and experimental situations. The aim of this study was to analyze whether dopamine depletion induces changes in the synaptology of the corpus striatum of rats after the unilateral injection of 6-OHDA. The findings suggest that after the lesion, both contralateral and ipsilateral striata exhibit an increased length of the synaptic ending in ipsilateral (since third day) and contralateral striatum (since Day 20), loss of axospinous synapses in ipsilateral striatum and a significant increment in the number of perforated synapses, suggesting brain plasticity that might be deleterious for the spines, because this type of synaptic contacts are presumably excitatory, and in the absence of the modulatory effects of dopamine, the neuron could die through excitotoxic mechanisms. Thus, we can conclude that the presence of perforated synapses after striatal dopamine depletion might be a form of maladaptive synaptic plasticity.

The combination of oral L-DOPA/rimonabant for effective dyskinesia treatment and cytological preservation in a rat model of Parkinson's disease and L-DOPA-induced dyskinesia.

Parkinson's disease is the second most prevalent neurodegenerative disease in the world. Its treatment is limited so far to the management of parkinsonian symptoms with L-DOPA (LD). The long-term use of LD is limited by the development of L-DOPA-induced dyskinesias and dystonia. However, recent studies have suggested that pharmacological targeting of the endocannabinoid system may potentially provide a valuable therapeutic tool to suppress these motor alterations. In the present study, we have explored the behavioral (L-DOPA-induced dyskinesias severity) and cytological (substantia nigra compacta neurons and striatum neuropil preservation) effects of the oral coadministration of LD and rimonabant, a selective antagonist of CB1 receptors, in the 6-hydroxydopamine rat model of Parkinson's disease. Oral coadministration of LD (30 mg/kg) and rimonabant (1 mg/kg) significantly decreased abnormal involuntary movements and dystonia, possibly through the conservation of some functional tyrosine hydroxylase-immunoreactive dopaminergic cells, which in turn translates into a well-preserved neuropil of a less denervated striatum. Our results provide anatomical evidence that long-term coadministration of LD with cannabinoid antagonist-based therapy may not only alleviate specific motor symptoms but also delay/arrest the degeneration of striatal and substantia nigra compacta cells.

Manganese mixture inhalation is a reliable Parkinson disease model in rats.

Manganese (Mn) is an essential trace metal. Regardless of its essentiality, it has been reported that the overexposure causes neurotoxicity manifested as extrapyramidal symptoms similar to those observed in Parkinson disease (PD). Recently, our group reported that mice that inhaled for 5 months the mixture of manganese chloride (MnCl(2)) and manganese acetate Mn(OAc)(3) developed movement abnormalities, significant loss of substantia nigra compacta (SNc) dopaminergic neurons, dopamine depletion and improved behavior with l-DOPA treatment. However, this model has only been characterized in mice. In order to have a well-supported and generalizable model in rodents, we used male Wistar rats that inhaled a mixture of 0.04 M MnCl(2) and 0.02 M Mn(OAc)(3), 1h three times a week for 6 months. Before Mn exposure, animals were trained to perform motor tests (Beam-walking and Single-pellet reaching tasks) and were evaluated each week after the exposure. The mixture of MnCl(2)/Mn(OAc)(3) caused alterations in the motor tests, 75.95% loss of SNc dopaminergic neurons, and no cell alterations in Globus Pallidus or striatum. With these results we conclude that the inhalation of the mixture of Mn compounds is a useful model in rodents for the study of PD.

Effect of chronic L-dopa or melatonin treatments after dopamine deafferentation in rats: dyskinesia, motor performance, and cytological analysis.

The present study examines the ability of melatonin to protect striatal dopaminergic loss induced by 6-OHDA in a rat model of Parkinson's disease, comparing the results with L-DOPA-treated rats. The drugs were administered orally daily for a month, their therapeutic or dyskinetic effects were assessed by means of abnormal involuntary movements (AIMs) and stepping ability. At the cellular level, the response was evaluated using tyrosine hydroxylase immunoreactivity and striatal ultrastructural changes to compare between L-DOPA-induced AIMs and Melatonin-treated rats. Our findings demonstrated that chronic oral administration of Melatonin improved the alterations caused by the neurotoxin 6-OHDA. Melatonin-treated animals perform better in the motor tasks and had no dyskinetic alterations compared to L-DOPA-treated group. At the cellular level, we found that Melatonin-treated rats showed more TH-positive neurons and their striatal ultrastructure was well preserved. Thus, Melatonin is a useful treatment to delay the cellular and behavioral alterations observed in Parkinson's disease.