Modulation of Brain β-Endorphin Concentration by the Specific Part of the Y Chromosome in Mice

International audienceBackground: Several studies in animal models suggest a possible effect of the specific part of the Y-chromosome (Y NPAR) on brain opioid, and more specifically on brain b-endorphin (BE). In humans, male prevalence is found in autistic disorder in which observation of abnormal peripheral or central BE levels are also reported. This suggests gender differences in BE associated with genetic factors and more precisely with Y NPAR. Methodology/Principal Findings: Brain BE levels and plasma testosterone concentrations were measured in two highly inbred strains of mice, NZB/BlNJ (N) and CBA/HGnc (H), and their consomic strains for the Y NPAR. An indirect effect of the Y NPAR on brain BE level via plasma testosterone was also tested by studying the correlation between brain BE concentration and plasma testosterone concentration in eleven highly inbred strains. There was a significant and major effect (P,0.0001) of the Y NPAR in interaction with the genetic background on brain BE levels. Effect size calculated using Cohen's procedure was large (56% of the total variance). The variations of BE levels were not correlated with plasma testosterone which was also dependent of the Y NPAR. Conclusions/Significance: The contribution of Y NPAR on brain BE concentration in interaction with the genetic background is the first demonstration of Y-chromosome mediated control of brain opioid. Given that none of the genes encompassed by the Y NPAR encodes for BE or its precursor, our results suggest a contribution of the sex-determining region (Sry, carried by Y NPAR) to brain BE concentration. Indeed, the transcription of the Melanocortin 2 receptor gene (Mc2R gene, identified as the proopiomelanocortin receptor gene) depends on the presence of Sry and BE is derived directly from proopiomelanocortin. The results shed light on the sex dependent differences in brain functioning and the role of Sry in the BE system might be related to the higher frequency of autistic disorder in males

The genetics of intersexual aggression in the laboratory mouse

Intersexual aggression was observed during an early experiment concerning the effects of XX male sex-reversal on aggressive and mating behavior. Subjects were from the FVB/NTacfBR strain. Roughly 50% of the subject males were observed to attack females in the mating behavior tests. In the breeding colony, females exhibited a wounding pattern indicative of receiving multiple flank bites. Flank biting is characteristic of male mouse offensive agonistic behavior. A review of the literature on intersexual aggression in mammalian males revealed two common features to male on female intersexual aggression: (1) estrous cycling should modulate aggressive behavior toward females, and (2) there is a positive relationship between the propensity for intermale and intersexual aggression within individuals. The experiments here describe how genotype (FVB/NTacfBR males vs. C57BL/6J males) interacted with these two common features. First, cycling interacted with genotype. FVB males increased the rate of attacks toward estrous females relative to diestrous females. B6 males were not aggressive toward females. Second, prior intermale aggressive experience had only subtle interactive effects with cycling and genotype in increasing intersexually aggressive behavior. A third experiment tested the hypothesis that hippocampal mossy fibers mediate the effects of genetic factors on intermale and intersexual aggression. It is known that there is a negative correlation between the size of the hippocampal intra- and infrapyramidal mossy fiber fields (IIPMF) and intermale aggression. Some evidence also supports such a negative relationship between IIPMF size and intersexual aggression. To test this, early postnatal transient hyperthyroidism was induced by injections of thyroxine into FVB/N pups from days 1–12. This treatment is known to increase the size of IIPMF. Experimental subjects did not differ from saline and no treatment controls on measures of intermale and intersexual aggression. Hypotheses for why this relationship did not exist were examined. Overall, these experiments identified the importance of cycling effects on intersexual aggression in the male mouse. They also enhanced the understanding of the relationship between genotype, intermale and intersexual aggression.