Diabetes and Depression: A Bidirectional Phenomenon

Diabetes mellitus is a strong molecular etiological upstream event that leads to different pathological problems like Cardio-vascular disease, nephropathy, neuropathy, retinopathy, hearing loss, and immunological disturbances, the most common of which is depression. Diabetes and depression relationship is thought to be bidirectional, meaning that depression can lead to diabetes and diabetes can assist the onset of depression. Depression is one of the most overlooked symptoms in diabetes patients, and it is strongly related to a decline in quality of life. Several pathological links are discussed in this review, including dysregulation of the hypothalamic pituitary-adrenal (HPA) axis and neurotransmitter systems, particularly the monoaminergic system, the role of oxidative stress, neuroinflammation, and cell death, impaired neurogenesis and BDNF synthesis, particularly in the hippocampus and prefrontal cortex, brain areas that regulate emotional behaviour, and finally, epigenetic factors.

Neuropathology of the Brainstem to Mechanistically Understand and to Treat Alzheimer’s Disease

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder as yet without effective therapy. Symptoms of this disorder typically reflect cortical malfunction with local neurohistopathology, which biased investigators to search for focal triggers and molecular mechanisms. Cortex, however, receives massive afferents from caudal brain structures, which do not only convey specific information but powerfully tune ensemble activity. Moreover, there is evidence that the start of AD is subcortical. The brainstem harbors monoamine systems, which establish a dense innervation in both allo- and neocortex. Monoaminergic synapses can co-release neuropeptides either by precisely terminating on cortical neurons or, when being “en passant”, can instigate local volume transmission. Especially due to its early damage, malfunction of the ascending monoaminergic system emerges as an early sign and possible trigger of AD. This review summarizes the involvement and cascaded impairment of brainstem monoaminergic neurons in AD and discusses cellular mechanisms that lead to their dysfunction. We highlight the significance and therapeutic challenges of transmitter co-release in ascending activating system, describe the role and changes of local connections and distant afferents of brainstem nuclei in AD, and summon the rapidly increasing diagnostic window during the last few years.

Astrocyte-derived TNF and glutamate critically modulate microglia reactivity by methamphetamine

Methamphetamine (Meth) is a powerful illicit psychostimulant, widely used for recreational purposes. Besides disrupting the monoaminergic system and promoting oxidative brain damage, Meth also causes neuroinflammation that contributes to synaptic dysfunction and behavioral deficits. Aberrant activation of microglia, the largest myeloid cell population in the brain, is a common feature in neurological disorders linked to cognitive impairment and neuroinflammation. In this study, we investigated the mechanisms underlying the aberrant activation of microglia elicited by Meth in the adult mouse brain. We found that binge Meth exposure caused microgliosis and disrupted risk assessment behavior (a feature that usually occurs in human Meth abusers), both of which required astrocyte-to-microglia crosstalk. Mechanistically, Meth triggered a detrimental increase of glutamate exocytosis from astrocytes (in a manner dependent on TNF production and calcium mobilization), promoting microglial expansion and reactivity. Ablating TNF production or suppressing astrocytic calcium mobilization prevented microglia reactivity and abolished the behavioral phenotype elicited by Meth exposure. Overall, our data indicate that glial crosstalk is critical to relay behavioral alterations caused by acute Meth exposure.One Sentence SummaryGlial crosstalk under methamphetamine exposure

Emotional intelligence, empathy, extraversion, alexithymia, environmentally responsible behavior in students-carriers of different MAOA, COMT gene genotypes

The article is devoted to the study of the association of genotypes of genes of monoamine oxidase A (MAOA) and catechol-O-methyltransferase (COMT) with emotional intelligence and personality traits of young people, such as extraversion-introversion, empathy, and alexithymia. The work was attended by students-psychologists, in the amount of 100 people. The following methods were used: Test of emotional intelligence (D.V. Lyusin); Emotional Empathy Questionnaire (A. Mehrabian, N. Epstein); «Big five» test; Toronto Alexithymia Scale. For statistical processing of the results obtained, we used multivariate analysis of variance ANOVA with Tukey’s post hoc analysis for non-equilibrium sample sizes. As a result, it was found that the genes of the monoaminergic system COMT and MAOA are associated with the general level of emotional intelligence. Women, in general, showed a lower level of emotional intelligence. The Met/Met genotype of the COMT gene is associated with a higher level of emotional intelligence and high extraversion. The Val/Met genotype of the COMT gene in women is associated with low emotional intelligence and low empathy. The Val/Val genotype of the COMT gene in men is associated with extraversion. In the work, no associations were found between the genotypes of the MAOA, COMT genes, and the level of alexithymia.

Monoterpenes alter TAR1-driven physiology in Drosophila species

ABSTRACTMonoterpenes are molecules with insecticide properties whose mechanism of action is, however, not completely elucidated. Furthermore, they seem to be able to modulate the monoaminergic system and several behavioural aspects in insects. In particular, tyramine (TA) and octopamine (OA) and their associated receptors orchestrate physiological processes such as feeding, locomotion and metabolism. Here, we show that monoterpenes not only act as biopesticides in Drosophila species but also can cause complex behavioural alterations that require functional type 1 tyramine receptors (TAR1s). Variations in metabolic traits as well as locomotory activity were evaluated in both Drosophila suzukii and Drosophila melanogaster after treatment with three monoterpenes. A TAR1-defective D. melanogaster strain (TAR1PL00408) was used to better understand the relationships between the receptor and monoterpene-related behavioural changes. Immunohistochemistry analysis revealed that, in the D. melanogaster brain, TAR1 appeared to be mainly expressed in the pars intercerebralis, lateral horn, olfactory and optic lobes and suboesophageal ganglion lobes. In comparison to wild-type D. melanogaster, the TAR1PL00408 flies showed a phenotype characterized by higher triglyceride levels and food intake as well as lower locomotory activity. The monoterpenes, tested at sublethal concentrations, were able to induce a downregulation of the TAR1 coding gene in both Drosophila species. Furthermore, monoterpenes also altered the behaviour in wild-type D. suzukii and D. melanogaster 24 h after continuous monoterpene exposure. Interestingly, they were ineffective in modifying the physiological performance of TAR1-defective flies. In conclusion, it appears that monoterpenes not only act as biopesticides for Drosophila but also can interfere with Drosophila behaviour and metabolism in a TAR1-dependent fashion.