With the wide access to studies of selected gene expressions in transgenic animals, mice have become the dominant species as cerebral disease models. Many of these studies are performed on animals of not more than eight weeks, declared as adult animals. Based on the earlier reports that full brain maturation requires at least three months in rats, there is a clear need to discern the corresponding minimal animal age to provide an "adult brain" in mice in order to avoid modulation of disease progression/therapy studies by ongoing developmental changes. For this purpose, we have studied anatomical brain alterations of mice during their first six months of age. Using T2-weighted and diffusion-weighted MRI, structural and volume changes of the brain were identified and compared with histological analysis of myelination. Mouse brain volume was found to be almost stable already at three weeks, but cortex thickness kept decreasing continuously with maximal changes during the first three months. Myelination is still increasing between three and six months, although most dramatic changes are over by three months. While our results emphasize that mice should be at least three months old when adult animals are needed for brain studies, preferred choice of one particular metric for future investigation goals will result in somewhat varying age windows of stabilization.

Leptin targets the brain to regulate feeding, neuroendocrine function and metabolism. The leptin receptor is present in hypothalamic centers controlling energy metabolism as well as in the centrally projecting Edinger–Westphal nucleus (EWcp), a region implicated in the stress response and in various aspects of stress-related behaviors. We hypothesized that the stress response by cocaine- and amphetamine-regulated transcript (CART)-producing EWcp-neurons would depend on the animal’s energy state. To test this hypothesis, we investigated the effects of changes in energy state (mimicked by low, normal and high leptin levels, which were achieved by 24 h fasting, normal chow and leptin injection, respectively) on the response of CART neurons in the EWcp of rats subjected or not to acute restraint stress. Our data show that leptin treatment alone significantly increases CART mRNA expression in the rat EWcp and that in leptin receptor deficient (db/db) mice, the number of CART producing neurons in this nucleus is reduced. This suggests that leptin has a stimulatory effect on the production of CART in the EWcp under non-stressed condition. Under stressed condition, however, leptin blunts stress-induced activation of EWcp neurons and decreases their CART mRNA expression. Interestingly, fasting, does not influence the stress-induced activation of EWcp-neurons, and specifically EWcp-CART neurons are not activated. These results suggest that the stress response by the EWcp depends to some degree on the animal’s energy state, a mechanism that may contribute to a better understanding of the complex interplay between obesity and stress.

Selective serotonin reuptake inhibitors (SSRI), such as fluoxetine, are used as first-line antidepressant medication during pregnancy. Since SSRIs cross the placenta the unborn child is exposed to the maternal SSRI medication, resulting in, amongst others, increased risk for autism in offspring. This likely results from developmental changes in brain function. Studies employing rats lacking the serotonin transporter have shown that elevations in serotonin levels particularly affect the development of the whisker related part of the primary somatosensory (barrel) cortex. Therefore, we hypothesized that serotonin level disturbances during development alter brain activity related to whisker stimulation. We treated female dams with fluoxetine or vehicle from gestational day 11 onwards for 21 days. We investigated offspring’s brain activity during whisker stimulation using functional magnetic resonance imaging (fMRI) at adolescence and adulthood. Our results indicate that adolescent offspring displayed increased activity in hippocampal subareas and the mammillary body in the thalamus. Adult offspring exhibited increased functional activation of areas associated with (higher) sensory processing and memory such as the hippocampus, perirhinal and entorhinal cortex, retrospinal granular cortex, piriform cortex and secondary visual cortex. Our data imply that perinatal SSRI exposure leads to complex alterations in brain networks involved in sensory perception and processing.