Dogmas and unsolved problems in brain sex differentiation

Throughout the animal kingdom, nervous systems differ between sexes. Sexual dimorphisms in neuroanatomical, physiological, and neurochemical parameters are reflected by sex-specific forms of behavior, in particular with regard to reproduction, and sex differences in neuroendocrine regulation. The present volume of Biomedical Reviews is mainly concerned with sex differences in the mammalian and human brain. However, it should at least be mentioned that the most convincing correlations between neuroanatomical and behavioral data have been provided by studies of the sexual differentiation of song control systems in bird species, in which the males sing and the females do not. In mammals, research used to locus on the hypothalamus commonly seen as the center for control of reproductive behavior and integration of hormonal and neural responses of the organism. We have therefore asked A. Matsumoto and Y. Arai to review the evidence for the hypothesis that sexually dimorphic functions of the hypothalamus are indeed based on a sex-specific neural circuitry. Notwithstanding the central role of the hypothalamus, it is important to note that more and more, often subtle, anatomical and/or functional sex differences have been and continue to be detected in other areas of the central nervous system. Of particular interest are sex differences in neural systems than are known.Biomedical Reviews 1997; 7: 1-3

HP1-β is required for development of the cerebral neocortex and neuromuscular junctions

HP1 proteins are thought to be modulators of chromatin organization in all mammals, yet their exact physiological function remains unknown. In a first attempt to elucidate the function of these proteins in vivo, we disrupted the murine Cbx1 gene, which encodes the HP1-β isotype, and show that the Cbx1−/−-null mutation leads to perinatal lethality. The newborn mice succumbed to acute respiratory failure, whose likely cause is the defective development of neuromuscular junctions within the endplate of the diaphragm. We also observe aberrant cerebral cortex development in Cbx1−/− mutant brains, which have reduced proliferation of neuronal precursors, widespread cell death, and edema. In vitro cultures of neurospheres from Cbx1−/− mutant brains reveal a dramatic genomic instability. Our results demonstrate that HP1 proteins are not functionally redundant and that they are likely to regulate lineage-specific changes in heterochromatin organization

Functional Evidence of Multidrug Resistance Transporters (MDR) in Rodent Olfactory Epithelium

Background: P-glycoprotein (Pgp) and multidrug resistance-associated protein (MRP1) are membrane transporter proteins which function as efflux pumps at cell membranes and are considered to exert a protective function against the entry of xenobiotics. While evidence for Pgp and MRP transporter activity is reported for olfactory tissue, their possible interaction and participation in the olfactory response has not been investigated. Principal Findings: Functional activity of putative MDR transporters was assessed by means of the fluorometric calcein acetoxymethyl ester (calcein-AM) accumulation assay on acute rat and mouse olfactory tissue slices. Calcein-AM uptake was measured as fluorescence intensity changes in the presence of Pgp or MRP specific inhibitors. Epifluorescence microscopy measured time course analysis in the olfactory epithelium revealed significant inhibitor-dependent calcein uptake in the presence of each of the selected inhibitors. Furthermore, intracellular calcein accumulation in olfactory receptor neurons was also significantly increased in the presence of either one of the Pgp or MRP inhibitors. The presence of Pgp or MRP1 encoding genes in the olfactory mucosa of rat and mouse was confirmed by RT-PCR with appropriate pairs of speciesspecific primers. Both transporters were expressed in both newborn and adult olfactory mucosa of both species. To assess a possible involvement of MDR transporters in the olfactory response, we examined the electrophysiological response to odorants in the presence of the selected MDR inhibitors by recording electroolfactograms (EOG). In both animal species