Dendritic Morphology of Hippocampal and Amygdalar Neurons in Adolescent Mice Is Resilient to Genetic Differences in Stress Reactivity

Many studies have shown that chronic stress or corticosterone over-exposure in rodents leads to extensive dendritic remodeling, particularly of principal neurons in the CA3 hippocampal area and the basolateral amygdala. We here investigated to what extent genetic predisposition of mice to high versus low stress reactivity, achieved through selective breeding of CD-1 mice, is also associated with structural plasticity in Golgi-stained neurons. Earlier, it was shown that the highly stress reactive (HR) compared to the intermediate (IR) and low (LR) stress reactive mice line presents a phenotype, with respect to neuroendocrine parameters, sleep architecture, emotional behavior and cognition, that recapitulates some of the features observed in patients suffering from major depression. In late adolescent males of the HR, IR, and LR mouse lines, we observed no significant differences in total dendritic length, number of branch points and branch tips, summated tip order, number of primary dendrites or dendritic complexity of either CA3 pyramidal neurons (apical as well as basal dendrites) or principal neurons in the basolateral amygdala. Apical dendrites of CA1 pyramidal neurons were also unaffected by the differences in stress reactivity of the animals; marginally higher length and complexity of the basal dendrites were found in LR compared to IR but not HR mice. In the same CA1 pyramidal neurons, spine density of distal apical tertiary dendrites was significantly higher in LR compared to IR or HR animals. We tentatively conclude that the dendritic complexity of principal hippocampal and amygdala neurons is remarkably stable in the light of a genetic predisposition to high versus low stress reactivity, while spine density seems more plastic. The latter possibly contributes to the behavioral phenotype of LR versus HR animals

Maternal high-fat diet prevents developmental programming by early-life stress

Anxiety disorders and depression are well-documented in subjects exposed to adverse childhood events. Recently, maternal obesity and/or maternal consumption of high-fat diets (HFD) have been also proposed as risk factors for offspring mental health. Here using an animal model in rats, we explored the combinatorial effects of a maternal HFD (40% of energy from fat without impact on maternal weight; during gestation and lactation) and maternal separation (MS) in offspring. In the prefrontal cortex (PFC) of pups, MS led to changes in the expression of several genes such as Bdnf (brain derived neurotrophic factor), 5HT-r1a (serotonin receptor 1a) and Rest4 (neuron-restrictive silencer element, repressor element 1, silencing transcription factor (Rest), splicing variant 4). Surprisingly, perinatal HFD strongly attenuated the developmental alterations induced by MS. Furthermore, maternal HFD totally prevented the endophenotypes (anxiety, spatial memory, social behavior, hypothalamic–pituitary–adrenal (HPA) axis response to stress, hippocampal neurogenesis and visceral pain) associated with MS at adulthood. Finally, we also demonstrated that HFD intake reduced anxiety and enhanced maternal care in stressed dams. Overall, our data suggest that a HFD restricted to gestation and lactation, which did not lead to overweight in dams, had limited effects in unstressed offspring, highlighting the role of maternal obesity, rather than fat exposure per se, on brain vulnerability during development.Environnement psychosocial précoce, empreintes biologiques et épigénétiques et état de santé à l'âge adult

Amphetamine sensitization in rats as an animal model of schizophrenia

Based on the 'endogenous dopamine sensitization' hypothesis of schizophrenia the present study employed a repeated amphetamine administration regime in order to investigate the behavioral, neurochemical and neuroanatomical consequences following short- and long-term withdrawal periods. The escalating amphetamine administration schedule consisted of three injections per day over a 6-day period with the dosage ranging from 1 to 8 mg/kg. It was demonstrated that following both short- (4 days) and long-term (66 days) withdrawal periods latent inhibition (LI) and prepulse inhibition (PPI), two translational paradigms highly relevant to schizophrenia, were disrupted. A challenge injection verified sensitization in two different cohorts of animals at 40 and 70 days following cessation of treatment. Neurochemical evaluation demonstrated a reduction in dopamine levels in the caudate-putamen and nucleus accumbens core and shell as well as an enhanced utilization ratio in the caudate-putamen after both withdrawal periods. Similar to the findings from post-mortem studies of brains of schizophrenic patients, a downregulation of glutamic acid decarboxylase 67 (GAD67) immunoreactivity was found in the hippocampus, prefrontal cortex, thalamus, and amygdala in amphetamine pretreated animals following longer withdrawal periods. This was not accompanied by enhanced neurotoxicity or reactive gliosis as demonstrated by the immunohistological analysis using the apoptotic marker activated Caspase-3 and GFAP (glial fibrillary acidic protein; a marker for astrocytes) following both short- and long-term withdrawal periods. In conclusion, it is suggested that these findings constitute a highly reliable and valid animal model of schizophrenia

Evidence of gender differences in the ability to inhibit brain activation elicited by food stimulation

Although impaired inhibitory control is linked to a broad spectrum of health problems, including obesity, the brain mechanism(s) underlying voluntary control of hunger are not well understood. We assessed the brain circuits involved in voluntary inhibition of hunger during food stimulation in 23 fasted men and women using PET and 2-deoxy-2[18F]fluoro-D-glucose (18FDG). In men, but not in women, food stimulation with inhibition significantly decreased activation in amygdala, hippocampus, insula, orbitofrontal cortex, and striatum, which are regions involved in emotional regulation, conditioning, and motivation. The suppressed activation of the orbitofrontal cortex with inhibition in men was associated with decreases in self-reports of hunger, which corroborates the involvement of this region in processing the conscious awareness of the drive to eat. This finding suggests a mechanism by which cognitive inhibition decreases the desire for food and implicates lower ability to suppress hunger in women as a contributing factor to gender differences in obesity