Creatine Activity as a Neuromodulator in the Central Nervous System.

Creatine is a nutritional compound that potentially influences cognitive processing and neuroprotection. Recent evidence has demonstrated that similar to neurotransmitters, creatine is released in an excitotoxic and action potential-dependent manner and acts as a neuromodulator. Creatine deficiency syndromes are characterized by severe mental and developmental disorders. Studies have reported that brain creatine content could be enhanced with creatine supplementation. Nevertheless, there is still limited knowledge about the effects of creatine on the central nervous system. However, ample evidence has proved the neuroprotective effects of creatine on various mental aspects, such as cognition, memory skills, and spatial memory. The present review aimed to review available experimental data and clinical observations confirming creatine roles in the central transmission process. A systematic search in the literature was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, and Google Scholar database using all available MeSH terms for Creatine, Phosphocreatine, Bioenergetics, Nervous system, Brain, Cognition, and Neuroprotection. Electronic database searches were combined and duplicates were removed. Here, first, creatine and its potential influence on cognitive health and performance were briefly reviewed. Next, the existing experimental and clinical evidence was specifically explored to understand how creatine could interact as a neurotransmitter in the nervous system. Studies have revealed that exogenous creatine supplementation decreases neuronal cell loss in experimental paradigms of neurological diseases. It was observed that creatine could interact with the N-methyl-D-aspartate receptor, Na+-K+-ATPase enzyme, GABAA receptor, serotonin 1A receptors, and presumably α1-adrenoceptor and play critical roles in the central transmission process which implies that creatine can be considered a neuromodulator.

Adherence to Healthy Eating Index-2015 and severity of disease in hospitalised military patients with COVID-19: a cross sectional study.

INTRODUCTION: Proper nutrition can play an important role in preventing and improving disease progression in patients with COVID-19. The Healthy Eating Index-2015 (HEI-2015) is one of the most common measures used to assess overall nutritional quality. This research aimed to identify the relationship between the HEI-2015 score and disease severity in hospitalised military patients with COVID-19. METHODS: This cross-sectional study was conducted in 295 hospitalised military patients (retired military and military reserve) with COVID-19. A validated food frequency questionnaire was used to assess food intake. To evaluate the quality of the diet, the HEI-2015 score was calculated. A multiple logistic regression analysis was performed to measure the association between HEI-2015 scores and disease severity (intensive care unit (ICU) admission and length of hospital stay greater than 4 days) in hospitalised military patients with COVID-19. RESULTS: The mean HEI-2015 score was significantly higher in non-ICU patients than in ICU patients (58.39±15.02 vs 53.54±15.65, p=0.01). After adjusting for possible confounding factors including age, sex, comorbidities, calorie intake, body mass index and physical activity, adherence to HEI-2015 inversely related to ICU admission (OR 0.98; 95% CI 0.95 to 1.00) and length of hospital stay of more than 4 days (OR 0.99; 95% CI 0.97 to 1.00) in hospitalised military patients with COVID-19, although statistically not significant. CONCLUSIONS: According to the results of the study, adherence to HEI-2015 inversely related to both ICU admission and length of hospital stay in hospitalised military patients with COVID-19, although it was not statistically significant.

Alterations in CA1 pyramidal neuronal intrinsic excitability mediated by Ih channel currents in a rat model of amyloid beta pathology.

Amyloid beta (Aß) accumulation plays an important role in the pathogenesis of Alzheimer's disease (AD) by changing the neuronal excitability. However, the cellular mechanisms by which accumulation of Aß affects intrinsic neuronal properties are not well understood. The effect of bilateral intra-frontal cortex Aß (1-42) peptide injection on the intrinsic excitability of hippocampal CA1 pyramidal neurons with particular focus on the contribution of hyperpolarization-activated (Ih) channel currents was examined using whole-cell patch-clamp recording. Passive avoidance memory impairment and morphological changes in rats receiving intra-frontal Aß treatment were observed, which was associated with significant changes both in passive and active intrinsic electrical membrane properties of CA1 pyramidal neurons. Electrophysiological recording showed a significant decrease in neuronal excitability associated with an augmentation in the first spike after-hyperpolarization (AHP) amplitude. In addition, the depolarizing sag voltage was altered in neurons recorded from Aß-treated group. In voltage-clamp condition, a hyperpolarizing activated inward current sensitive to ZD7288 and capsaicin was significantly increased in neurons from Aß-treated rats. The Ih current density was increased and the activation curve was shifted toward less negative potential in the Aß-treated group as compared to control group. The enhancing effect of Aß treatment on Ih current was confirmed by showing upregulation of the mRNA of HCN1 channel in the CA1 pyramidal layer of hippocampi. These findings suggest the contribution of Ih and possibly TRPV1 channel currents to the changes induced by Aß treatment in the intrinsic membrane properties, which, in turn, may provide therapeutic targets for treatment of AD.