It is well-known that hyaluronic acid (HA) as a component of brain extracellular matrix (ECM) plays a pivotal role in the nervous system and is involved in synaptic plasticity changes in vascular cognitive impairment and dementia. HA breakdown is a feature of the acute stage of stroke injury and may be detrimental through enhancement of the inflammatory response. Recent studies have shown that knockout mice lacking hyaluronic acid synthetase demonstrates epileptic phenotype in vivo and removal of HA leads to delayed development of epileptiform activity in cultured hippocampal neurons in vitro. Here, we studied whether digestion of hyaluronic acid in the hippocampus in early postnatal period can trigger seizures. Hyaluronidase (Hyal) (5 U/μl) was bilaterally injected into C57BL/6j mice (P17) CA1 field of hippocampus using the stereotaxic method to remove hyaluronan-based ECM. Transcriptome analysis of hippocampal tissue 2 h after enzymatic digestion of hyaluronan-based brain ECM revealed increased gene expression of proteins involved in inflammation reactions (TLR2, CCL2,3,5), neuroinflammation, axonal guidance and ephrin receptor signaling, versus the vehicle group. Mice injected with hyaluronidase exhibited delayed audiogenic seizures and improvement in working memory 72 h after injection, while there were no changes in locomotor activity, anxious level and exploratory behavior due to the open field test. The obtained results point to a link between the activation of neuroinflammation by enzymatic digestion of hyaluronan-based brain ECM during the neonatal period and their subsequent reactivity to seizures, which may play an important role in the functional features of the developing brain, including its seizure propensity.

No abstract

In recent years, much of the attention paid to theoretical and applied biomedicine, as well as neurobiology, has been drawn to various aspects of sexual dimorphism due to the differences that male and female brain cells demonstrate during aging: (a) a dimorphic pattern of response to therapy for neurodegenerative disorders, (b) different age of onset and different degrees of the prevalence of such disorders, and (c) differences in their symptomatic manifestations in men and women. The purpose of this review is to outline the genetic and epigenetic differences in brain cells during aging in males and females. As a result, we hereby show that the presence of brain aging patterns in males and females is due to a complex of factors associated with the effects of sex chromosomes, which subsequently entails a change in signal cascades in somatic cells.