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In humans, mutations of this gene cause Rett syndrome, a rare disorder of the neural development that causes, among other ailments, a reduction of language and of their capacity to roam, traits of autistic diseases and epilepsy.
Nonapeptides, peptide chains with nine amino acids like oxytocin and vasopressin, are found in the cerebral nuclei that regulate social behavior, which is why they’ve been proposed, particularly oxytocin, as possible therapies for autism disorders and associated syndromes.
Rett syndrome is a rare disorder of the neural development caused by mutations to gene Mecp2, which mainly affects young girls, and which had traditionally been categorized under the umbrella of autism disorders.
To examine if the nonapeptidergic systems are impaired in Rett syndrome, which would consequently justify their use as therapeutic targets, the group has analyzed them at the mind of an Mecp2-null mouse brain.
The study has been co-directed by Carmen Agustín-Pavón, professor at the UV and researcher at the Mixed Unit for the Research of Functional Neuroanatomy, that comprises staff in the Department of Cellular Biology, Functional Biology and Physical Anthropology of the UV and the Predepartmental Unit of Medicine of the UJI, also by Mónica Santos, from the Middle of Neuroscience and Cellular Biology from the University of Coimbra, thing That Has also taken part in the study, together with the University Otto-von-Guericke in Germany.
Carmen Agustín explains that”oxytocinergic and vasopressinergic substances in the brain are involved in guiding social behavior, which includes sexual dimorphism in mammals, and is consequently organized differently in males and females. By way of instance, vasopressinergic innervation is abundant in some cerebral nuclei, like the septum or lateral habenula, in males, whereas in females it’s virtually non-existent. Our analysis proves that Mecp2-null males have a significant reduction in this vasopressinergic innervation, which is contingent on the existence of high levels of testosterone, in most of the nuclei from we call the socio-sexual brain.”
In reality, according to Elena Martínez-Rodríguez, first signatory of this analysis,”as men using a schizophrenic Mecp2 have internal testicles, our theory is that the effect we find in the vasopressinergic system can happen indirectly, as a result of the shortage of testosterone, and this is necessary for the dimorphic sexual development of the male brain.”
Both vasopressin and testosterone are involved in regulating the social and aggressive male behavior of mice. This is why we study the response of mutant males compared to other members of the species in different situations, and we are finding that they are less aggressive than their healthy brothers, and that they prefer being near a caged member of their species to a greater extent than the healthy specimens.”-Ana Martín-Sánchez, Study First Co-Author, Pompeu Fabra University
This theory is backed by the very fact that mutant females show no deficit in their vasopressinergic system. Furthermore, as an indirect measure to the level of testosterone, the team analyzed the amount of sexual pheromones in urine, and confirmed that male pheromone darcin vanishes in mutant mice.
The study team did not find significant differences within the oxytocinergic system except for, in schizophrenic men,”a small drop in the oxytocinergic innervation of the lateral habenula”. Agustín-Pavón clarifies that”there do not seem to be significant deficits in the construction of the oxytocinergic system, and therefore our data does not back administering oxytocin for Rett.
Furthermore, the fact that there is a heightened social taste, and not diminished, such as in the conventional autism disorder models, is a motive for Rett to not be classified as one.”
The expert concludes:”our study demonstrates how, when studying animal models with alterations to their social behaviour, the probable ramifications of genetic mutations within the endocrine system has to be taken into consideration, because hormone levels directly affect the construction of the brain”
Asociación RUVID
Martínez-Rodríguez, E., et al. (2020)Male-specific features are reduced in Mecp2-null mice: analyses of vasopressinergic innervation, pheromone production and social behavior. Brain Structure and Function. doi.org/10.1007/s00429-020-02122-6.
