The Christian Orthodox Church Fasting Diet Is Associated with Lower Levels of Depression and Anxiety and a Better Cognitive Performance in Middle Life.

Lifestyle choices significantly influence mental health in later life. In this study we investigated the effects of the Christian Orthodox Church (COC) fasting diet, which includes long-term regular abstinence from animal-based products for half the calendar year, on cognitive function and emotional wellbeing of healthy adults. Two groups of fasting and non-fasting individuals were evaluated regarding their cognitive performance and the presence of anxiety and depression using the Mini Mental Examination Scale, the Hamilton Anxiety Scale, and the Geriatric Depression Scale (GDS), respectively. Data on physical activity, smoking, and vitamin levels were collected and correlated with mental health scoring. Negative binomial regression was performed to examine differences in the GDS scores between the two groups. Significantly lower levels of anxiety (7.48 ± 4.98 vs. 9.71 ± 5.25; p < 0.001) and depression (2.24 ± 1.77 vs. 3.5 ± 2.52; p < 0.001), along with better cognitive function (29.15 ± 0.79 vs. 28.64 ± 1.27; p < 0.001), were noticed in fasting compared to non-fasting individuals. GDS score was 31% lower (Incidence Rate Ratio: 0.69, 95% Confidence Interval: 0.56-0.85) in the fasting group compared to the control, while vitamin and ferrum levels did not differ. The COC fasting diet was found to have an independent positive impact on cognition and mood in middle-aged and elderly individuals

The Glutamate Dehydrogenase Pathway and Its Roles in Cell and Tissue Biology in Health and Disease

Glutamate dehydrogenase (GDH) is a hexameric enzyme that catalyzes the reversible conversion of glutamate to α-ketoglutarate and ammonia while reducing NAD(P)+ to NAD(P)H. It is found in all living organisms serving both catabolic and anabolic reactions. In mammalian tissues, oxidative deamination of glutamate via GDH generates α-ketoglutarate, which is metabolized by the Krebs cycle, leading to the synthesis of ATP. In addition, the GDH pathway is linked to diverse cellular processes, including ammonia metabolism, acid-base equilibrium, redox homeostasis (via formation of fumarate), lipid biosynthesis (via oxidative generation of citrate), and lactate production. While most mammals possess a single GDH1 protein (hGDH1 in the human) that is highly expressed in the liver, humans and other primates have acquired, via duplication, an hGDH2 isoenzyme with distinct functional properties and tissue expression profile. The novel hGDH2 underwent rapid evolutionary adaptation, acquiring unique properties that enable enhanced enzyme function under conditions inhibitory to its ancestor hGDH1. These are thought to provide a biological advantage to humans with hGDH2 evolution occurring concomitantly with human brain development. hGDH2 is co-expressed with hGDH1 in human brain, kidney, testis and steroidogenic organs, but not in the liver. In human cerebral cortex, hGDH1 and hGDH2 are expressed in astrocytes, the cells responsible for removing and metabolizing transmitter glutamate, and for supplying neurons with glutamine and lactate. In human testis, hGDH2 (but not hGDH1) is densely expressed in the Sertoli cells, known to provide the spermatids with lactate and other nutrients. In steroid producing cells, hGDH1/2 is thought to generate reducing equivalents (NADPH) in the mitochondria for the biosynthesis of steroidal hormones. Lastly, up-regulation of hGDH1/2 expression occurs in cancer, permitting neoplastic cells to utilize glutamine/glutamate for their growth. In addition, deregulation of hGDH1/2 is implicated in the pathogenesis of several human disorders

Glutamate-specific gene linked to human brain evolution enhances synaptic plasticity and cognitive processes

Summary: The human brain is characterized by the upregulation of synaptic, mainly glutamatergic, transmission, but its evolutionary origin(s) remain elusive. Here we approached this fundamental question by studying mice transgenic (Tg) for GLUD2, a human gene involved in glutamate metabolism that emerged in the hominoid and evolved concomitantly with brain expansion. We demonstrate that Tg mice express the human enzyme in hippocampal astrocytes and CA1-CA3 pyramidal neurons. LTP, evoked by theta-burst stimulation, is markedly enhanced in the CA3-CA1 synapses of Tg mice, with patch-clamp recordings from CA1 pyramidal neurons revealing increased sNMDA currents. LTP enhancement is blocked by D-lactate, implying that GLUD2 potentiates L-lactate-mediated astrocyte-neuron interaction. Dendritic spine density and synaptogenesis are increased in the hippocampus of Tg mice, which exhibit enhanced responses to sensory stimuli and improved performance on complex memory tasks. Hence, GLUD2 likely contributed to human brain evolution by enhancing synaptic plasticity and metabolic processes central to cognitive functions

&Tau;he Greek Variant in APP Gene: The Phenotypic Spectrum of APP Mutations

Mutations in the gene encoding amyloid precursor protein (APP) cause autosomal dominant inherited Alzheimer&rsquo;s disease (AD). We present a case of a 68-year-old female who presented with epileptic seizures, neuropsychiatric symptoms and progressive memory decline and was found to carry a novel APP variant, c.2062T&gt;G pLeu688Val. A comprehensive literature review of all reported cases of AD due to APP mutations was performed in PubMed and Web of Science databases. We reviewed 98 studies with a total of 385 cases. The mean age of disease onset was 51.3 &plusmn; 8.3 (31&ndash;80 years). Mutations were most often located in exons 17 (80.8%) and 16 (12.2%). The most common symptoms were dementia, visuospatial symptoms, aphasia, epilepsy and psychiatric symptoms. Mutations in the &beta;-amyloid region, and specifically exon 17, were associated with high pathogenicity and a younger age of disease onset. We describe the second reported APP mutation in the Greek population. APP mutations may act variably on disease expression and their phenotype is heterogeneous

High Prevalence of Transthyretin-Related Amyloidosis in Crete, Greece is Due to Three TTR Pathogenic Variants with Markedly Differing Phenotypic Presentations

Objective: To describe occurrence and clinical features of hereditary Transthyretin-Related Amyloidosis (hATTR) in Crete, Greece. Background: Over the past 27 years, we have diagnosed several hATTR patients presenting with heterogeneous clinical manifestations. Design/Methods: Since 1993, we evaluated 33 subjects, members of 12 unrelated families, for various reasons including polyneuropathy, cardiac involvement, visual symptoms and family history suggestive of hATTR. All patients underwent genetic testing and were positive for a pathogenic TTR variant. Results: Nineteen subjects (12 women) with the predominantly polyneuropathic phenotype were heterozygous for the p.Val50Met TTR mutation. The median age of symptom onset was 31 years (range 25 to 43 years). Common presenting manifestations were paresthesias, temperature sensory loss and weakness of the lower extremities, urinary difficulties, postural dizziness, diarrhea, and weight loss. Heart failure developed in 4 patients late in the disease course. Fourteen patients underwent orthotopic liver transplantation. Ten patients (4 females) with the predominantly cardiopathic phenotype harbored the p.Val114Ala TTR mutation. Their median age at onset was 69.8 years (range 54–78 years). These patients presented with congestive heart failure due to restrictive cardiomyopathy and showed cardiac amyloid deposition on 99mTc scintigraphy or biopsy. All patients had peripheral neuropathy, autonomic system involvement and carpal tunnel syndrome. By screening their offspring, 3 asymptomatic carriers of the p.Val114Ala TTR mutation were found. Finally, one 50-year old male with predominantly ocular involvement and positive family history of progressive visual loss harbored the p.Arg54Gly TTR change. Based on patients surviving in Crete in January 2019, we estimated the prevalence of hATTR on the island to be 35.3 per 1 million. Conclusions: Hereditary amyloidosis is common in Crete, Greece, placing the region among those with the highest hATTR frequency world-wide. The disease is caused by three different TTR pathogenic variants with markedly differing ages of onset and phenotypic expressions