Neudesin (also known as neuron derived neurotrophic factor, Nenf) is a scarcely studied putative non-canonical neurotrophic factor. In order to understand its function in the brain, we performed an extensive behavioral characterization (motor, emotional, and cognitive dimensions) of neudesin-null mice. The absence of neudesin leads to an anxious-like behavior as assessed in the elevated plus maze (EPM), light/dark box (LDB) and novelty suppressed feeding (NSF) tests, but not in the acoustic startle (AS) test. This anxious phenotype is associated with reduced dopaminergic input and impoverished dendritic arborizations in the dentate gyrus granule neurons of the ventral hippocampus. Interestingly, shorter dendrites are also observed in the bed nucleus of the stria terminalis (BNST) of neudesin-null mice. These findings lead us to suggest that neudesin is a novel relevant player in the maintenance of the anxiety circuitry.

Sex differences in the visual system have been reported in aspects of human vision, such as color perception, peripheral vision and even in the activation of the primary visual cortex. Similarly sex differences have been identified in the visual system of laboratory animals such as monkeys and rats. On the other hand, environmental enrichment (EE) has long been known to affect visual tissues. Taking into consideration the variation in the experimental approaches concerning EE and the sex differences in the visual system, we investigated in male and female rats the serotonergic and dopaminergic effects of EE in the retina and the visual cortex at different time points (i.e. P0-25, P0-P90 and P90-P150). Early EE in adulthood increased the serotonergic activity of the male visual cortex and the female retina (P0-P90). In addition early enrichment (P0-P90) increased dopaminergic activity in the female retina and in the visual cortex of both sexes. Late enrichment increased the serotonergic activity in the retina and visual cortex of both sexes (P90-P150), but increased the dopaminergic activity in the visual cortex only in male animals. In the present study we expose marked sex differences in the neurochemistry of visual tissues and we demonstrate for the first time that EE can in fact modify the serotonergic and dopaminergic neurotransmission in the retina and visual cortex. Overall, the present study underpins the sex-dependent neurochemical status of the visual system and provides insights into the different mechanisms underlying visual processing in the two sexes.

INTRODUCTION: Geriatric depression is a heterogeneous disorder with a complex genetic background. Current first-line treatment of depression is associated with a lower therapeutic outcome in aged depressed patients, when compared to younger subjects. Research which has explored this inadequate response has highlighted several factors which have come into play with the pharmacogenetics of antidepressants in the elderly being a particular area of interest. AREAS COVERED: The authors perform a critical review of the English language articles from PubMed using search terms such as late-life/geriatric depression, antidepressants, pharmacogenetics, pharmacogenomics, pharmacokinetic, genetic, genotype, remission, therapy, treatment and polymorphism. EXPERT OPINION: The emerging clinical and pharmacogenetic data are slowly unveiling the importance of the genome - age interaction in antidepressant response. This data introduces a critical new parameter in personalized medicine. A profound analysis of the age factor in the pharmacogenetics of antidepressant response is imperative, in order to elucidate the clinical significance of these findings and thereby improve patient treatment in the elderly.

INTRODUCTION: Sildenafil is the first effective oral treatment for male erectile dysfunction. Although it is generally accepted that its action is peripheral, it has been suggested that it influences central neural pathways that are involved in male sexual arousal. Recently, it was shown that local sildenafil administration enhances extracellular dopamine (DA) in the nucleus accumbens (NAcc). AIM: The aim of this study was to determine whether sildenafil administration alters dopaminergic and serotonergic activity in the NAcc and the medial preoptic area (mPOA) during a model of sexual arousal. METHODS: An acute (2 days) or chronic (21 days) sildenafil regimen (1 mg/kg) was administered intraperitoneally to male rats. Thirty minutes after the last sildenafil injection, all males were exposed to noncontact erection sessions by the presentation of inaccessible estrous females. Half of the males had previous experience of noncontact sexual encounter and the other half were exposed for the first time. MAIN OUTCOME MEASURES: Tissue levels of DA and its metabolites, 3,4-Dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), as well as serotonin (5-HT) and its metabolite 5-HIAA, were measured in the mPOA and NAcc with high-performance liquid chromatography with electrochemical detector. Dopamine ([DOPAC+HVA]/DA) and serotonin (5-HIAA/5-HT) turnovers were also calculated as indices of neurotransmission. RESULTS: In nontrained males, acute and chronic sildenafil treatment increased DA and 5-HT turnover rates in the mPOA and NAcc. In trained rats, acute sildenafil also increased DA and 5-HT turnover rates in both structures, whereas chronic treatment enhanced 5-HT turnover rate only in the mPOA and DA turnover rate only in the NAcc. CONCLUSIONS: Our data confirm that sildenafil enhances dopaminergic activity in the NAcc, extend these findings to the mPOA and furthermore, reveal sildenafil-induced effects on serotonergic activity in these brain regions as well. Therefore, present findings support an effect of sildenafil on central neural pathways that are involved in the control of sexual arousal.