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.

Sex differences in the neurobiology of responses to chronic stress have been widely discussed but remain poorly understood. We found that chronic unpredictable mild stress (CUMS) experienced during adolescence induced different behavioral patterns in adult males and females. Immunohistochemical analysis of the CA1 field of the dorsal and ventral hippocampus revealed no quantitative or morphological changes in astrocytes in the long term after CUMS. Real-time PCR analysis showed no increase in the expression level of SigmaR1 after CUMS relative to individual housekeeping genes. Analysis of mouse cerebral cortex homogenates showed that IL-1β levels only decreased after CUMS in males. However, the SigmaR1 levels were significantly higher in the CUMS groups than in the control groups in both sexes. It can be concluded that biological sex and age influence the response to CUMS, although not in all cases. Further studies are needed to understand the effects of chronic stress on males and females. This is important because men and women have different risks for stress and mental disorders.

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.

One of the promising and relevant directions in the treatment of oncological diseases is currently the development of a system for the delivery of antitumor drugs based on polyanions. Therefore, the aim of this work was to study the specifics of pharmacokinetics and biodistribution of a 5-Fluorouracil polymeric complex compared with commercial 5-Fluorouracil. Materials and methods: Monomeric methacrylic acid was used to synthesize polymers; 2-phenylpropane-2-ilbenzodithioate was used for the synthesis of poly(methacrylic acid). To study the molecular-weight characteristics of poly(methacrylic acid) by gel permeation chromatography, an experimental neoplasm model was obtained by grafting PC-1 cancer cells. Blood samples were drawn from the tail vein at different points in time. The rats were sacrificed via decapitation after drawing the last pharmacokinetic blood sample. To study the biodistribution, internal organs were isolated and analyzed. The measurements were carried out by high-performance liquid chromatography. Results: Our results demonstrate that incorporation in a polymeric complex changes the pharmacokinetics and biodistribution profile of 5-FU. The polymeric complex was shown to accumulate to a higher level in the lung and spleen. Conclusion: The results obtained are the basis for further studies to verify the efficacy of the 5-Fluorouracil polymeric complex.

The neurobiology of sex differences in response to chronic stress is a topic that has been extensively discussed in the scientific literature, but remains poorly understood. In our research, we found that chronic unpredictable mild stress (CUMS) experienced during adolescence induces different behavioural patterns in adult males и females. Similarly, immunohistochemical analysis of the CA1 field of the dorsal and ventral hippocampus revealed no changes in quantitative and morphological changes in astrocytes at long-term period after CUMS. Real-time PCR analysis showed no increase in SIGMAR1 expression level relative to individual housekeeping genes after CUMS. Analysis of mouse cerebral cortex homogenates showed that IL-1β levels decreased after stress modelling only in males. However, Sigma R1 levels were significantly higher in the CUMS group than in the controls in both sexes. It can be concluded that biological sex and age do indeed influence the response to CUMS, although not in all cases. There is a need for further research in order to understand the effects of chronic stress on males and females. This is of crucial importance because men and women are exposed to different risks in relation to stress and mental health.