The search for markers applicable for efficient differential diagnosis and personalized therapy is a priority task of experimental neuro-oncology. Modern molecular methods allow us to analyze human biopsy material; however, further actions with this extracted tumor tissue are limited. Relevant and sophisticated CNS tumor models are required for precise therapy development. Although it is possible to use human biomaterial to create 2D and 3D cultures and implant them into xenograft animals, the data generated from such models is limited. Due to changes in the classification of the CNS tumors in 2021, a representative model should have not only morphological similarity to human tumors but also key genetic aberrations for studying the mechanisms of carcinogenesis and personalized therapy (such as PDGFRa, Olig1/2, Sox2, and Mki67) for different glioma models such as astrocytoma, oligodendroglioma, and glioblastoma. On the basis of a unique scientific facility “The Collection of experimental tumors of the nervous system and neural tumor cell lines” (Avtsyn Research Institute of Human Morphology of “Petrovsky National Research Center of Surgery”), there is a biobank of chemically induced transplantable tumors of laboratory animals. Their properties, mechanisms, and progression closely correlate with malignant CNS neoplasms in humans. These are potentially useful for identifying novel signaling pathways associated with oncogenesis in the nervous system and personalizing therapeutic approaches. In our work, we characterized a tissue-transplantable brain tumor strain of rat glioma101.8 using MRI, IHC, scRNA-seq, and qPCR-RT methods. According to this study, the cellular composition of the tissue-transplantable rat glioma 101.8 strain was determined, as well as the major genetic signature characteristics of each cell population of this tissue-transplantable strain and its microenvironment.

Bisphenol A (BPA) is a widespread plasticizer widely used in the food industry worldwide. However, a consensus on the safe level of its daily intake does not currently exist, while there are numerous data pointing to a link between prenatal exposure to BPA and early neuropsychiatric disorders, such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). The global average human-equivalent dose of BPA is estimated at 30 ng/kg body weight/day. Thus, the research herein was conducted on newborn and juvenile rat offspring of both sexes delivered from rats treated with 30 ng/kg body weight/day orally from day 6 to 21 of pregnancy and for a further 21 days during lactation. Our data indicate that prenatal exposure to 30 ng/kg/day from gestation day 6 to delivery induced sexually dimorphic, region-specific alterations in the neonatal (PD1) rat brains, impacting inflammatory reactions, estrogen receptor signaling, and neural progenitor dynamics. Prenatally BPA-treated males exhibited a pro-inflammatory state characterized by an increased total number of ramified Iba1+ microglia cells in the hippocampus alongside upregulation of Aif1, Nfkb, Tnf, Il1b, and Hif1a. Conversely, prenatally BPA-treated females showed only an increased total number of hippocampal Iba1+ cells and displayed inflammatory resilience, lacking upregulation of these markers. Both sexes exhibited a pro-inflammatory state in the prefrontal cortex via upregulation of Nfkb, Tnf, Il1b, and Hif1a. While both sexes showed decreased Tgfb in the prefrontal cortex, they deployed distinct compensatory responses: males upregulated the neuroprotector Igf1 only in the hippocampus, whereas in females, it was upregulated in both the hippocampus and the prefrontal cortex. Estrogen receptor expression was also highly dimorphic. In the hippocampus, males displayed an imbalance via Esr1 upregulation and Esr2 downregulation, while females showed Esr2 downregulation alone. In the prefrontal cortex, these transcriptional profiles were the opposite. Finally, neural progenitor markers were altered. In the prefrontal cortex, BPA drove the upregulation of Sox2 and Pax6 in males but Sox9 in females; in the hippocampus, only Pax6 was upregulated, and only in males. The PAX6 protein level in the hippocampus was significantly increased in males but decreased in females. In juvenile offspring (PD21), behavioral patterns characterized by hyper-exploration, increased environmental investigation, and heightened emotional reactivity during social exposure were more pronounced in female offspring. These baseline neonatal disparities followed by behavioral changes underscore the necessity of sex-specific approaches when evaluating early-life neurodevelopment and subsequent adult behavioral and biological vulnerabilities.

Aging is associated with chronic pro-inflammatory background and increased risk of susceptibility to oxidative stress and neurodegenerative processes. However, age-dependent morphological and molecular changes in glial cells under chronic oxidative stress remain insufficiently characterized. This study aimed to investigate age- and region-specific alterations in astrocytes and microglia in the hippocampus and the entorhinal cortex (EntC) of adult (4–6 months) and old (22–24 months) male Wistar rats following chronic AlCl₃ administration (100 mg/kg/day for 60 days). Spatial learning and memory were assessed using the Morris water maze. GFAP+ astrocytes and Iba1+ microglia were evaluated by immunohistochemistry and morphometry. Hippocampal 4-HNE and pTau (Ser404) were assessed by ELISA and Western blotting, respectively. Hippocampal expression of Tnf, Tgfb, Mmp9, Bdnf, Ntrk2, and Gpx4 was evaluated by RT-qPCR, while serum MMP-9 and HSP-70 concentrations were measured by ELISA. Aging was associated with increased glial cell size in both brain regions, elevated hippocampal Tnf expression, decreased Tgfb and Ntrk2 expression, and increased serum MMP-9 and HSP-70 serum concentrations. In adult rats, AlCl₃ exposure was accompanied by changes in astrocytic morphology and increased Iba1+ cell density in the EntC, whereas molecular compensatory mechanisms remained preserved in the hippocampus. Only old AlCl₃-treated rats demonstrated reduced success in locating the former platform position in the Morris water maze and significantly elevated hippocampal 4-HNE levels, consistent with increased lipid peroxidation. Although hippocampal pTau (Ser404) immunoreactivity showed an age-related increase, no statistically significant effect of AlCl₃ exposure or age + AlCl₃ was detected. In this group, AlCl₃ exposure was associated with increased Iba1+ cell density in both regions, hypertrophic astrocytic morphology in the hippocampus, and reduced astrocytic area with fragmented processes in the EntC. These changes coincided with decreased hippocampal Bdnf and Gpx4 expression, as well as co-existence of reduced serum MMP-9 and HSP-70 concentrations. Overall, these findings demonstrate that aging influences region-specific glial morphological alterations and associated molecular responses to chronic AlCl₃-induced oxidative stress. This model demonstrated a translational approach to provide insights regarding mechanisms of age-related neurodegeneration.