Wojciech Glac

Artykuł podejmuje problem granic w dydaktyce z perspektywy neurobiologii. Granice są tu rozumiane nie tylko jako strukturalne ramy regulujące role, normy i oczekiwania, lecz także jako bodźce generujące nowość, zaskoczenie i konflikt poznawczy – a więc błędy przewidywania uruchamiające procesy neuroplastyczne. Autor omawia mechanizmy neuronalne stojące za wykrywaniem nowości (rola hipokampa, ciała migdałowatego, kory przedczołowej, układu nagrody i sieci wielkoskalowych mózgu) oraz pokazuje, w jaki sposób umiarkowany stres może pełnić funkcję katalizatora uczenia się, podczas gdy stres przewlekły i nadmierny prowadzi do reakcji unikania, utrwalania lęku i spadku motywacji. Tekst analizuje także indywidualne predyspozycje do przekraczania granic – wynikające z interakcji czynników genetycznych, neurobiologicznych i doświadczeń edukacyjnych – oraz ich konsekwencje dla eksploracji, tolerancji niepewności i elastyczności poznawczej. W zakończeniu wskazano, że odpowiednio projektowane sytuacje dydaktyczne, łączące nowość z poczuciem bezpieczeństwa i przyzwoleniem na błąd, pozwalają twórczo wykorzystać granice jako narzędzie świadomego wspierania rozwoju, ciekawości i adaptacyjnych strategii radzenia sobie z niepewnością.

The article addresses educational boundaries from a neurobiological perspective. Boundaries are understood not only as structural frames that regulate roles, norms and expectations, but also as triggers of novelty, surprise and cognitive conflict–that is, prediction errors that activate neuroplastic processes. The author discusses the neural mechanisms underlying novelty detection (the role of the hippocampus, amygdala, prefrontal cortex, reward system and large-scale brain networks) and shows how moderate stress can act as a catalyst for learning, whereas excessive or chronic stress leads to avoidance, consolidation of fear and decreased motivation. The text also analyses individual predispositions to crossing boundaries, resulting from the interaction of genetic, neurobiological and experiential factors, and their consequences for exploration, tolerance of uncertainty and cognitive flexibility. In conclusion, the article argues that carefully designed educational situations which combine novelty with a sense of safety and permission to err can harness boundaries as a tool for consciously fostering development, curiosity and adaptive strategies for dealing with uncertainty and unpredictability.

Cannabidiol (CBD), the major non-psychotropic compound of Cannabis sp. , is an effective treatment for inflammatory and autoimmune diseases and produces various anti-tumor effects but the mechanisms of its long-term actions in vivo remain unclear. We have previously shown that CBD administration (5 mg/kg) in healthy rats significantly decreased lymphocyte numbers in peripheral blood, involving B, T CD4+ and T CD8+ lymphocyte subsets, but not natural killer (NK) cells. To examine the effects of CBD on lymphocyte subsets in the spleen and NK cellular cytotoxicity (NKCC), adult male Wistar rats (n = 63) were administered intraperitoneal injections of CBD (2.5 or 5 mg/kg/day) for 14 consecutive days and lymphocyte counts were obtained using flow cytometry. NKCC in the peripheral blood and spleen was quantified using a Chromium-51 release assay. Furthermore, CB ₂ receptors were blocked using selective receptor antagonist AM630 (1 mg/kg). The results indicate that repeated administration of CBD at a dose of 5 mg/kg/day resulted in a decrease in splenic lymphocyte number, involving T and B lymphocytes but not NK cells. The decrease in lymphocyte number was partially blocked by pretreatment with CB ₂ receptor antagonist while no changes in NKCC were observed following CBD administration. These results reveal that in healthy rats, CBD produces similar lymphopenic effects in the spleen as it does in peripheral blood and that the effects of CBD on lymphocyte numbers in vivo are at least partially mediated by CB ₂ receptors.

The modulation of dopamine transmission evokes strong behavioural effects that can be achieved by commonly used psychoactive drugs such as haloperidol or cocaine. Cocaine non-specifically increases dopamine transmission by blocking dopamine active transporter (DAT) and evokes behavioural arousal, whereas haloperidol is a non-specific D2-like dopamine receptor antagonist with sedative effects. Interestingly, dopamine has been found to affect immune cells in addition to its action in the central nervous system. Here, we address the possible interactions between haloperidol and cocaine and their effects on both immune cells and behaviour in freely moving rats. We use an intravenous model of haloperidol and binge cocaine administration to evaluate the drugs' impact on the distribution of lymphocyte subsets in both the peripheral blood and the spleen. We assess the drugs' behavioural effects by measuring locomotor activity. Cocaine evoked a pronounced locomotor response and stereotypic behaviours, both of which were completely blocked after pretreatment with haloperidol. The results suggest that blood lymphopenia, which was induced by haloperidol and cocaine (except for natural killer T cells), is independent of D2-like dopaminergic activity and most likely results from the massive secretion of corticosterone. Haloperidol pretreatment prevented the cocaine-induced decrease in NKT cell numbers. Moreover, the increased systemic D2-like dopaminergic activity after cocaine administration is a significant factor in retaining T CD3⁺ CD4⁺ lymphocytes and non-T/NK CD45RA⁺ cells in the spleen.

Purpose: Intracerebroventricular-(ICV)-streptozotocin-(STZ)-induced neuroinflammation is a model of Alzheimer’s disease (AD) compatible with the inflammation hypothesis of ageing (“inflammaging” state). Previously, we observed age-dependent (young vs aged) dimethyl fumarate (DMF)-induced anti-inflammatory and neuroprotective effects in the brain along with improvement in cognitive functions in rats with the ICV-STZ-induced model of AD. To evaluate whether DMF reduces neuroinflammation based on the peripheral inflammatory response inhibition, we determined peripheral inflammatory mediators in young and aged rats with the ICV-STZ-induced AD pathology following DMF therapy. Materials and Methods: Young (4-month-old) and aged (22-month-old) rats were fed with 0.4% DMF rat chow for 21 consecutive days after ICV-STZ (3 mg/ventricle) injections. After behavioral testing, blood and spleens were collected to determine the numbers of leukocytes (WBC), lymphocytes and their subpopulations, haematological parameters, the concanavalin (Con)-A-induced production and plasma concentration of interferon (IFN)-γ, interleukin (IL)-6, IL-10 and corticosterone (COR). Results: Age-dependent anti-inflammatory effect of the DMF treatment in rats with ICV-STZ injections manifested as decreased peripheral WBC and lymphocyte numbers, including TCD3⁺CD4⁺CD8⁻, TCD3⁺CD4⁻CD8⁺, B (CD45RA⁺) and NK (161a⁺), in aged rats. Furthermore, DMF lowered the blood and spleen lymphocyte production of pro-inflammatory IFN-γ and IL-6 in young and aged rats, whereas it enhanced the plasma level of anti-inflammatory IL-10 and lymphocyte’s ability to produce it in aged rats only. In parallel to changes in peripheral WBC numbers in the model of AD, DMF decreased the red blood cell number, haemoglobin concentration, haematocrit and mean platelet volume in aged, but not young, rats. In contrast to controls, DMF did not influence the COR response in STZ groups. Conclusion: Besides preventing neuroinflammation, DMF acts on the pro-/anti-inflammatory balance in the periphery and causes an anti-inflammatory shift in T lymphocytes which could contribute to DMF’s therapeutic effects in the ICV-STZ-induced model of AD, in particular, in aged rats.

Modulation of dopamine transmission evokes strong behavioral effects that can be achieved by psychoactive drugs such as haloperidol or cocaine. Cocaine non-specifically increases dopamine transmission by blocking dopamine active transporter (DAT) and evokes behavioral arousal, while haloperidol is a non-specific dopamine D2 receptor antagonist with sedative effects. Interestingly, dopamine has been found to affect immune cells in addition to its action in the central nervous system. Here we address the possible interactions between haloperidol and cocaine and their effects on both immune cells and behavior in freely moving rats. We use an intravenous model of haloperidol and binge cocaine administration to evaluate the drugs’ impact on the distribution of lymphocyte subsets in both the peripheral blood and the spleen. We assess the drugs’ behavioral effects by measuring locomotor activity. Cocaine evoked a pronounced locomotor response and stereotypic behaviors, both of which were completely blocked after pretreatment with haloperidol. The results suggest that blood lymphopenia which was induced by haloperidol and cocaine (except for NKT cells), is independent of dopaminergic activity and most likely results from the massive secretion of corticosterone. Haloperidol pretreatment prevented the cocaine-induced decrease in NKT cell numbers. On the other hand, the increased systemic dopaminergic activity after cocaine administration is a significant factor in retaining T CD4 ⁺ and B lymphocytes in the spleen. Abstract Figure:

Deep brain stimulation of the subthalamic nucleus (DBS-STN) is an effective treatment for advanced motor symptoms of Parkinson’s disease (PD). Recently, a connection between the limbic part of the STN and side effects of DBS-STN has been increasingly recognized. Animal studies have shown that DBS-STN influences behavior and provokes neurochemical changes in regions of the limbic system. Some of these regions, which are activated during DBS-STN, are involved in neuroimmunomodulation. The therapeutic effects of DBS-STN in PD treatment are clear, but the influence of DBS-STN on peripheral immunity has not been reported so far. In this study, we examined the effects of unilateral DBS-STN applied in male Wistar rats with 6-hydroxydopamine PD model (DBS-6OHDA) and rats without nigral dopamine depletion (DBS) on corticosterone (CORT) plasma concentration, blood natural killer cell cytotoxicity (NKCC), leukocyte numbers, lymphocyte population and apoptosis numbers, plasma interferon gamma (IFN-γ), interleukin 6 (IL-6), and tumor necrosis factor (TNF-α) concentration. The same peripheral immune parameters we measured also in non-stimulated rats with PD model (6OHDA). We observed peripheral immunity changes related to PD model. The NKCC and percentage of T cytotoxic lymphocytes were enhanced, while the level of lymphocyte apoptosis was down regulated in 6OHDA and DBS-6OHDA groups. After DBS-STN (DBS-6OHDA and DBS groups), the plasma CORT and TNF-α were elevated, the number of NK cells and percentage of apoptosis were increased, while the number of B lymphocytes was decreased. We also found, changes in plasma IFN-γ and IL-6 levels in all the groups. These results suggest potential peripheral immunomodulative effects of DBS-STN in the rat model of PD. However, further studies are necessary to explain these findings and their clinical implication.

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