Abstract
BackgroundMicroRNAs indirectly orchestrate myriads of essential biological processes. A wide diversity of miRNAs of the neurodevelopmental importance characterizes the brain tissue, which, however, exhibits region-specific miRNA profile differences. One of the most conservative regions of the brain is periaqueductal grey (PAG) playing vital roles in significant functions of this organ, also those observed to be sex-influenced. The domestic pig is an important livestock species but is also believed to be an excellent human model. This is of particular importance for neurological research because of the similarity of pig and human brains as well as difficult access to human samples. However, the pig PAG profile has not been characterized so far. Moreover, molecular bases of sex differences connected with brain functioning, including miRNA expression profiles, have not been fully deciphered yet.MethodsThus, in this study, we applied next-generation sequencing to characterize pig PAG expressed microRNAs. Furthermore, we performed differential expression analysis between females and males to identify changes of the miRNA profile and reveal candidates underlying sex-related differences.ResultsAs a result, known brain-enriched, and new miRNAs which will expand the available profile, were identified. The downstream analysis revealed 38 miRNAs being differentially expressed (DE) between female and male samples. Subsequent pathway analysis showed that they enrich processes vital for neuron growth and functioning, such as long-term depression and axon guidance. Among the identified sex-influenced miRNAs were also those associated with the PAG physiology and diseases related to this region.ConclusionsThe obtained results broaden the knowledge on the porcine PAG miRNAome, along with its dynamism reflected in different isomiR signatures. Moreover, they indicate possible mechanisms associated with sex-influenced differences mediated via miRNAs in the PAG functioning. They also provide candidate miRNAs for further research concerning, i.e., sex-related bases of physiological and pathological processes occurring in the nervous system.Graphical abstract
Highlights
MicroRNAs indirectly orchestrate myriads of essential biological processes
Summing up, taking into account the important role that the periaqueductal grey (PAG) plays in the functioning of the brain, the aim of our work was to characterize its Differentially expressed microRNAs (miRNAs) profile, including the identification of new miRNAs expressed in this region, as well as shed some light on the potential roles of miRNAs in shaping sex specific differences
The comprehensive analysis of the miRNAome profile of the porcine PAG tissue enabled us to determine conservative miRNAs characteristic for the brain tissue, such as miR-9, -26a, and -99a-5p. This is the first study to reveal the repertoire of potentially novel sequences and isomiR signatures in the pig PAG region, which sheds some light on the multifaceted influence of miRNA expression on brain functioning and gives a stimulus for future research
Summary
MicroRNAs indirectly orchestrate myriads of essential biological processes. A wide diversity of miRNAs of the neurodevelopmental importance characterizes the brain tissue, which, exhibits region-specific miRNA profile differences. The domestic pig (Sus scrofa) is an important animal for livestock production and from the biomedical point of view as an alternate, large mammal model organism for the human [1,2,3] This especially applies to neurological research because of the similarity of brain development (the growth pattern and the extent of peak brain growth at the time of birth), anatomy (i.e., gyral pattern and distribution of gray and white matter), and size between pigs and humans [4]. The pig is considered to be of great potential for broadening the knowledge of general neuronal and behavioral processes, as a subject of central nervous system (CNS) research, including neuroanatomy, neurobiology, and cognitive neuroscience [4] It is postulated for validation as an animal model for neurological and neuropsychiatric diseases such as schizophrenia and Alzheimer’s disease. It may be affected in many disorders, such as migraine [11], Wernicke’s encephalopathy [12], multiple sclerosis (MS) [13], and stroke [14, 15]
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