Chronic Stress, Depression, and Alzheimer's Disease: The Triangle of Oblivion.

Chronic stress and high levels of the main stress hormones, and glucocorticoids (GC), are implicated in susceptibility to brain pathologies such as depression and Alzheimer's disease (AD), as they promote neural plasticity damage and glial reactivity, which can lead to dendritic/synaptic loss, reduced neurogenesis, mood deficits, and impaired cognition. Moreover, depression is implicated in the development of AD with chronic stress being a potential link between both disorders via common neurobiological underpinnings. Hereby, we summarize and discuss the clinical and preclinical evidence related to the detrimental effect of chronic stress as a precipitator of AD through the activation of pathological mechanisms leading to the accumulation of amyloid ß (Aß) and Tau protein. Given that the modern lifestyle increasingly exposes individuals to high stress loads, it is clear that understanding the mechanistic link(s) between chronic stress, depression, and AD pathogenesis may facilitate the treatment of AD and other stress-related disorders.

Chronic pain causes Tau-mediated hippocampal pathology and memory deficits.

Persistent pain has been recently suggested as a risk factor for dementia. Indeed, chronic pain is frequently accompanied by maladaptive brain plasticity and cognitive deficits whose molecular underpinnings are poorly understood. Despite the emerging role of Tau as a key regulator of neuronal plasticity and pathology in diverse brain disorders, the role of Tau has never been studied in the context of chronic pain. Using a peripheral (sciatic) neuropathy to model chronic pain in mice-spared nerve injury (SNI) for 4 months-in wildtype as well as P301L-Tau transgenic mice, we hereby demonstrate that SNI triggers AD-related neuropathology characterized by Tau hyperphosphorylation, accumulation, and aggregation in hippocampus followed by neuronal atrophy and memory deficits. Molecular analysis suggests that SNI inhibits autophagy and reduces levels of the Rab35, a regulator of Tau degradation while overexpression of Rab35 or treatment with the analgesic drug gabapentin reverted the above molecular changes leading to neurostructural and memory recovery. Interestingly, genetic ablation of Tau blocks the establishment of SNI-induced hippocampal morphofunctional deficits supporting the mediating role of Tau in SNI-evoked hippocampal pathology and memory impairment. These findings reveal that exposure to chronic pain triggers Tau-related neuropathology and may be relevant for understanding how chronic pain precipitates memory loss leading to dementia.

[Pharmacology of ketamine and esketamine as rapid-acting antidepressants].

The lack of utter efficacy and fast action of commonly used antidepressants that selectively target the monoaminergic neurotransmission has led to the exploration of ketamine's actions. Ketamine's antidepressant effect was firstly described in 1973 and nowadays its therapeutic value as a fast- and long- lasting antidepressant has been extensively established. Ketamine is an antagonist of the N-Methyl-D-aspartate receptor (NMDAR) and its main mechanism of action via NMDAR inhibition expressed in GABAergic (gamma-Aminobutyric acid, GABA) interneurons may be relayed to its antidepressant effects. This review aims to describe the pharmacokinetic and pharmacodynamic profile of ketamine when used for treatment-resistant depression. Moreover, ketamine is a racemic mixture consisting of two enantiomers, R- and S- ketamine. We describe the pharmacology of esketamine, along with the guidelines for effective and safe intranasal administration of esketamine. Lastly, this review presents sex differences in preclinical and clinical studies of ketamine and esketamine administration.

Development of the Greek version of the Face Name Associative Memory Exam (GR-FNAME12) in cognitively normal elderly individuals.

OBJECTIVE: The Face-Name Associative Memory Examination (FNAME) is a cross-modal associative memory test with a high sensitivity for detecting Alzheimer's disease-related subtle memory problems at an early preclinical stage. The present study examined the psychometric characteristics of a Greek version of the short form of FNAME (GR-FNAME12) to evaluate the contribution of demographic characteristics, report the range of performance within our sample, and estimate regression-based norms in cognitively normal elderly individuals. METHOD: In all, 216 cognitively normal elderly individuals were recruited and were administered a version of the short form of the FNAME (GR-FNAME12) that was culture and language specific to Greek-speaking individuals and developed for this study. RESULTS: The construct validity of GR-FNAME12 was determined using principal component analysis thereby revealing two factors: face-name and face-occupation. These match the original version of the test. A significant positive correlation between GR-FNAME12 and two traditional memory measures - the RAVLT and the ROCFT - supported convergent validity. Test-retest reliability was computed for 32 participants. Multiple regression analyses showed that only age and not education or gender significantly predicted performance on the GR-FNAME12. We also estimated regression-based norms for the GR-FNAME12 scales. CONCLUSION: It was found that the Greek version of the FNAME12 had adequate psychometric properties, and could be administered to Greek-speaking individuals for clinical and research purposes.