Impaired Dynamics of Positional and Contextual Neural Coding in an Alzheimer's Disease Rat Model.

Background: The hippocampal representation of space, formed by the collective activity of populations of place cells, is considered as a substrate of spatial memory. Alzheimer's disease (AD), a widespread severe neurodegenerative condition of multifactorial origin, typically exhibits spatial memory deficits among its early clinical signs before more severe cognitive impacts develop. Objective: To investigate mechanisms of spatial memory impairment in a double transgenic rat model of AD. Methods: In this study, we utilized 9-12-month-old double-transgenic TgF344-AD rats and age-matched controls to analyze the spatial coding properties of CA1 place cells. We characterized the spatial memory representation, assessed cells' spatial information content and direction-specific activity, and compared their population coding in familiar and novel conditions. Results: Our findings revealed that TgF344-AD animals exhibited lower precision in coding, as evidenced by reduced spatial information and larger receptive zones. This impairment was evident in maps representing novel environments. While controls instantly encoded directional context during their initial exposure to a novel environment, transgenics struggled to incorporate this information into the newly developed hippocampal spatial representation. This resulted in impairment in orthogonalization of stored activity patterns, an important feature directly related to episodic memory encoding capacity. Conclusions: Overall, the results shed light on the nature of impairment at both the single-cell and population levels in the transgenic AD model. In addition to the observed spatial coding inaccuracy, the findings reveal a significantly impaired ability to adaptively modify and refine newly stored hippocampal memory patterns.

Glucose disturbances in non-diabetic patients receiving acute treatment with methylprednisolone pulses.

OBJECTIVE: Methylprednisolone pulses are used in a variety of disease conditions, both for acute and chronic therapy. Although well tolerated, they increase glucose levels in both non-diabetic and diabetic patients. They may also be considered a significant risk for acute metabolic alterations. The purpose of this report is to determine the metabolic changes in blood glucose levels in non-diabetic patients receiving methylprednisolone pulses and identify the presence of predictive factors for its development. METHODS: Observational, prospective study in 50 non-diabetic patients receiving 1 g intravenous methylprednisolone pulses for three consecutive days as an indication for diverse autoimmune disorders. Demographic, anthropometric, and metabolic variables were analyzed, and glucose, insulin and C-peptide levels after each steroid pulse were identified. Different variables and the magnitude of hyperglycemia were analyzed using Pearson's correlation. RESULTS: 50 patients were included, predominantly women (66%, n = 33). The average age was 41 ± 14 years with a BMI of 26 ± 3 kg/m². Baseline glucose was 83 ± 10 mg/dL. After each steroid pulse, glucose increased to 140 ± 28, 160 ± 38 and 183 ± 44, respectively (p < 0.001). C-peptide and insulin concentrations increased significantly (p < 0.001). The prevalence of fasting hyperglycemia after each pulse was 68%, 94% and 98%, respectively. We found no correlation between the magnitude of hyperglycemia and the studied variables. CONCLUSION: Methylprednisolone pulses produced significant increases in fasting glucose in most patients without diabetes. Further studies are needed to define its role in long-term consequences.

Glucose disturbances in non-diabetic patients receiving acute treatment with methylprednisolone pulses / Distúrbios de glicose em pacientes não diabéticos que recebem tratamento agudo com pulsos de metilprednisolona

OBJECTIVE: Methylprednisolone pulses are used in a variety of disease conditions, both for acute and chronic therapy. Although well tolerated, they increase glucose levels in both non-diabetic and diabetic patients. They may also be considered a significant risk for acute metabolic alterations. The purpose of this report is to determine the metabolic changes in blood glucose levels in non-diabetic patients receiving methylprednisolone pulses and identify the presence of predictive factors for its development. METHODS: Observational, prospective study in 50 non-diabetic patients receiving 1 g intravenous methylprednisolone pulses for three consecutive days as an indication for diverse autoimmune disorders. Demographic, anthropometric, and metabolic variables were analyzed, and glucose, insulin and C-peptide levels after each steroid pulse were identified. Different variables and the magnitude of hyperglycemia were analyzed using Pearson's correlation. RESULTS: 50 patients were included, predominantly women (66 percent, n = 33). The average age was 41 ± 14 years with a BMI of 26 ± 3 kg/m². Baseline glucose was 83 ± 10 mg/dL. After each steroid pulse, glucose increased to 140 ± 28, 160 ± 38 and 183 ± 44, respectively (p < 0.001). C-peptide and insulin concentrations increased significantly (p < 0.001). The prevalence of fasting hyperglycemia after each pulse was 68 percent, 94 percent and 98 percent, respectively. We found no correlation between the magnitude of hyperglycemia and the studied variables. CONCLUSION: Methylprednisolone pulses produced significant increases in fasting glucose in most patients without diabetes. Further studies are needed to define its role in long-term consequences.

OBJETIVO: Pulsos de metilprednisolona são usados em diversas doenças, tanto para tratamento agudo quanto crônico. Embora bem tolerados, eles aumentam os níveis de glicose em ambos os pacientes, não diabéticos e diabéticos. Eles também podem ser considerados um risco significativo para alterações metabólicas agudas. O propósito deste estudo é determinar as alterações metabólicas nos níveis de glicose no sangue de pacientes não diabéticos que recebem pulsos de metilprednisolona e identificar a presença de fatores preditivos para seu desenvolvimento. MÉTODOS: Estudo observacional prospectivo em 50 pacientes não diabéticos que recebem pulsoterapia com 1 g de metilprednisolona intravenosa por três dias consecutivos como tratamento para diversas doenças autoimunes. Variáveis demográficas, antropométricas e metabólicas foram analisadas, e glicose, insulina e níveis de peptídeo C foram identificados após cada pulso de esteroide. Diferentes variáveis e a magnitude da hiperglicemia foram analisadas utilizando a correlação de Pearson. RESULTADOS: 50 pacientes foram incluídos, predominantemente mulheres (66 por cento, n = 33). A idade média foi de 41 ± 14 anos com um IMC de 26 ± 3 kg/m². A glicose de base foi de 83 ± 10 mg/dL. Após cada pulso de esteroide, a glicose aumentou para 140 ± 28, 160 ± 38 e 183 ± 44, respectivamente (p < 0,001). Peptídeo C e concentrações de insulina aumentaram significativamente (p < 0,001). A prevalência de hiperglicemia em jejum após cada pulso foi de 68 por cento, 94 por cento e 98 por cento, respectivamente. Não encontramos nenhuma correlação entre a magnitude da hiperglicemia e as variáveis estudadas. CONCLUSÃO: Os pulsos de metilprednisolona produziram aumentos significativos na glicemia de jejum na maioria dos pacientes sem diabetes. Mais estudos são necessários para definir o seu papel nas consequências em longo prazo.