Impact of Serotonin Transporter Absence on Brain Insulin Receptor Expression, Plasma Metabolome Changes, and ADHD-like Behavior in Mice fed a Western Diet.

The impaired function of the serotonin transporter (SERT) in humans has been linked to a higher risk of obesity and type 2 diabetes, especially as people age. Consuming a "Western diet" (WD), which is high in saturated fats, cholesterol, and sugars, can induce metabolic syndrome. Previous research indicated that mice carrying a targeted inactivation of the gene (knockout, KO) and fed a WD display significant metabolic disturbances and behaviors reminiscent of ADHD.

Relationship among α‑synuclein, aging and inflammation in Parkinson's disease (Review).

Parkinson's disease (PD) is a common neurodegenerative pathology whose major clinical symptoms are movement disorders. The main pathological characteristics of PD are the selective death of dopaminergic (DA) neurons in the pars compacta of the substantia nigra and the presence of Lewy bodies containing α-synuclein (α-Syn) within these neurons. PD is associated with numerous risk factors, including environmental factors, genetic mutations and aging.

Molecular signature of excessive female aggression: study of stressed mice with genetic inactivation of neuronal serotonin synthesis.

Aggression is a complex social behavior, critically involving brain serotonin (5-HT) function. The neurobiology of female aggression remains elusive, while the incidence of its manifestations has been increasing. Yet, animal models of female aggression are scarce.

Serotonin Transporter (SERT) Expression Modulates the Composition of the Western-Diet-Induced Microbiota in Aged Female Mice.

The serotonin transporter (SERT), highly expressed in the gut and brain, is implicated in metabolic processes. A genetic variant of the upstream regulatory region of the gene encoding SERT, the so-called short (s) allele, in comparison with the long (l) allele, results in the decreased function of this transporter, altered serotonergic regulation, an increased risk of psychiatric pathology and type-2 diabetes and obesity, especially in older women. Aged female mice with the complete (: KO) or partial (: HET) loss of SERT exhibit more pronounced negative effects following their exposure to a Western diet in comparison to wild-type (: WT) animals.

Understanding the Role of Oxidative Stress, Neuroinflammation and Abnormal Myelination in Excessive Aggression Associated with Depression: Recent Input from Mechanistic Studies.

Aggression and deficient cognitive control problems are widespread in psychiatric disorders, including major depressive disorder (MDD). These abnormalities are known to contribute significantly to the accompanying functional impairment and the global burden of disease. Progress in the development of targeted treatments of excessive aggression and accompanying symptoms has been limited, and there exists a major unmet need to develop more efficacious treatments for depressed patients.

Hippocampal Over-Expression of Cyclooxygenase-2 (COX-2) Is Associated with Susceptibility to Stress-Induced Anhedonia in Mice.

The phenomenon of individual variability in susceptibility/resilience to stress and depression, in which the hippocampus plays a pivotal role, is attracting increasing attention. We investigated the potential role of hippocampal cyclooxygenase-2 (COX-2), which regulates plasticity, neuroimmune function, and stress responses that are all linked to this risk dichotomy. We used a four-week-long chronic mild stress (CMS) paradigm, in which mice could be stratified according to their susceptibility/resilience to anhedonia, a key feature of depression, to investigate hippocampal expression of COX-2, a marker of microglial activation Iba-1, and the proliferation marker Ki67.

Altered behaviour, dopamine and norepinephrine regulation in stressed mice heterozygous in TPH2 gene.

Gene-environment interaction (GxE) determines the vulnerability of an individual to a spectrum of stress-related neuropsychiatric disorders. Increased impulsivity, excessive aggression, and other behavioural characteristics are associated with variants within the tryptophan hydroxylase-2 (Tph2) gene, a key enzyme in brain serotonin synthesis. This phenotype is recapitulated in naïve mice with complete, but not with partial Tph2 inactivation.

Metabolic, Molecular, and Behavioral Effects of Western Diet in Serotonin Transporter-Deficient Mice: Rescue by Heterozygosity?

Reduced function of the serotonin transporter (SERT) is associated with increased susceptibility to anxiety and depression and with type-2 diabetes, which is especially true in older women. Preference for a "Western diet" (WD), enriched with saturated fat, cholesterol, and sugars, may aggravate these conditions. In previous studies, decreased glucose tolerance, central and peripheral inflammation, dyslipidemia, emotional, cognitive, and social abnormalities were reported in WD-fed young female mice.

Geoclimatology and sleep in Africa: A mini-review.

Sleeping habits and morningness-eveningness questionnaires (chronotype), and polysomnography (internal sleep organization) were proposed to healthy volunteers living under natural climates from different locations in West Africa (Niger, Côte d'Ivoire) and Central Africa (Angola, Congo). Under the Sahelian dry climate, 138 Niger medical students (130 had afternoon naps) completed 1792 sleep questionnaires during 7-day sessions in the cool-dry and hot-dry seasons. As everywhere else on Earth, daily sleep lasted 7 to 8hours.

Cerebral inducible nitric oxide synthase protein expression in microglia, astrocytes and neurons in Trypanosoma brucei brucei-infected rats.

To study the anatomo-biochemical substrates of brain inflammatory processes, Wistar male rats were infected with Trypanosoma brucei brucei. With this reproducible animal model of human African trypanosomiasis, brain cells (astrocytes, microglial cells, neurons) expressing the inducible nitric oxide synthase (iNOS) enzyme were revealed. Immunohistochemistry was achieved for each control and infected animal through eight coronal brain sections taken along the caudorostral axis of the brain (brainstem, cerebellum, diencephalon and telencephalon).

Serotonin: its place today in sleep preparation, triggering or maintenance.

Serotonin (5-HT) is involved in sleep in two different ways. First, when released during waking by the axonal nerve endings, it influences the synthesis of hypnogenic substances in specific brain targets. Such a synthesis might be in keeping with the waking qualitative aspects.

Stress-induced hippocampus Npas4 mRNA expression relates to specific psychophysiological patterns of stress response.

Neuronal Per-Arnt-Sim (PAS) domain protein 4 (Npas4) is a key protein that intervenes in GABA synapse scaling and neurotrophicity enhancing. Since GABA and neurotrophicity are implicated in stress response and Npas4-deficient rodents exhibit behavioral alterations, an investigation was designed in rats to verify whether stress-induced spontaneous hippocampus Npas4 mRNA expression would be associated with specific patterns of stress response. The rats were exposed to one of three stressor levels: no stress (CTL, n = 15), exposure to a footshock apparatus (Sham, S, n = 40) and footshock (F, n = 80).

Autism-Like Behaviours and Memory Deficits Result from a Western Diet in Mice.

Nonalcoholic fatty liver disease, induced by a Western diet (WD), evokes central and peripheral inflammation that is accompanied by altered emotionality. These changes can be associated with abnormalities in social behaviour, hippocampus-dependent cognitive functions, and metabolism. Female C57BL/6J mice were fed with a regular chow or with a WD containing 0.

Sleep patterns in villagers and urban African volunteers in a humid tropical climate: Influence of accessibility to electric light?

Recent publications focusing on sleep-wake alternation, using actigraphic recordings in hunter-gatherers, stressed the existence of a potential effect of electricity availability on sleep habits. These reports prompted us to achieve a new analysis of the polysomnographic data already obtained in healthy African volunteers in equatorial Africa during two different investigations. Comparison of the 24-h polysomnographic sleep patterns were done between 9 volunteers sleeping in a laboratory in Abidjan (Abidjan cohort) and 11 villagers living in electricity-free bush villages (Sinfra cohort).

Dicholine succinate, the neuronal insulin sensitizer, normalizes behavior, REM sleep, hippocampal pGSK3 beta and mRNAs of NMDA receptor subunits in mouse models of depression.

Central insulin receptor-mediated signaling is attracting the growing attention of researchers because of rapidly accumulating evidence implicating it in the mechanisms of plasticity, stress response, and neuropsychiatric disorders including depression. Dicholine succinate (DS), a mitochondrial complex II substrate, was shown to enhance insulin-receptor mediated signaling in neurons and is regarded as a sensitizer of the neuronal insulin receptor. Compounds enhancing neuronal insulin receptor-mediated transmission exert an antidepressant-like effect in several pre-clinical paradigms of depression; similarly, such properties for DS were found with a stress-induced anhedonia model.

Deuterium content of water increases depression susceptibility: the potential role of a serotonin-related mechanism.

Environmental factors can significantly affect disease prevalence, including neuropsychiatric disorders such as depression. The ratio of deuterium to protium in water shows substantial geographical variation, which could affect disease susceptibility. Thus the link between deuterium content of water and depression was investigated, both epidemiologically, and in a mouse model of chronic mild stress.

Agomelatine restores a physiological response to stress in the aged rat.

Short duration immobilization stress (IS) in younger rats is followed by a sleep rebound involving slow wave sleep (SWS) and, more particularly, rapid eye movement (REM) sleep. This rebound, expressing the ability of the brain to confront a stress challenge, is now accepted as a marker of the homeostasis. In older rats (24-25 months), however, an IS of 1h is not followed by a sleep rebound.

Expression patterns of c-Fos early gene and phosphorylated ERK in the rat brain following 1-h immobilization stress: concomitant changes induced in association with stress-related sleep rebound.

An immobilization stress (IS) of 1 h applied at the beginning of the dark phase is followed by a sleep rebound. During the restraint, serotonin released by the dorsal raphe nucleus within the arcuate area stimulates the availability of corticotropin-like intermediate lobe peptide (CLIP or ACTH18-39). Three hours after the restraint, CLIP, through its hypnogenic properties, contributes to the sleep rebound that follows the IS.

The neuronal insulin sensitizer dicholine succinate reduces stress-induced depressive traits and memory deficit: possible role of insulin-like growth factor 2.

Background: A number of epidemiological studies have established a link between insulin resistance and the prevalence of depression. The occurrence of depression was found to precede the onset of diabetes and was hypothesized to be associated with inherited inter-related insufficiency of the peripheral and central insulin receptors. Recently, dicholine succinate, a sensitizer of the neuronal insulin receptor, was shown to stimulate insulin-dependent H2O2 production of the mitochondrial respiratory chain leading to an enhancement of insulin receptor autophosphorylation in neurons.

d-Serine diffusion through the blood-brain barrier: effect on d-serine compartmentalization and storage.

d-Serine is a co-agonist of N-methyl-d-aspartate (NMDA) receptors. It has been implicated in the etiology of schizophrenia and has shown efficacy as an adjuvant to reduce positive and negative symptoms of schizophrenia. In addition, d-serine can modulate cognition in animals when administered alone.

Nitric oxide in the regulation of the sleep-wake states.

Nitric oxide (NO) production involves four different NO-synthases (NOSs) that are either constitutive (neuronal, nNOS; endothelial, eNOS; mitochondrial, mNOS) or inducible (iNOS) in nature. Three main processes regulate NO/NOSs output, i.e.