Jolanta Helena Kotlinska

Background/Objectives: Post-traumatic stress disorder (PTSD) is associated with systemic alterations that may involve the gastrointestinal tract, yet intestinal responses to fear-related learning remain poorly characterized. We investigated intestinal mucosal morphology, MUC2 immunoreactivity, and local immune responses following fear conditioning and extinction, and assessed their modulation by the selective dopamine transporter inhibitor CE-123. Methods: Twenty-four adolescent female Wistar rats were assigned to Control or fear-conditioned (FC) groups receiving Vehicle or CE-123 (10 mg/kg, i.p.) during the extinction phase. Morphometry and immunohistochemical detection of CD68, CD206, iNOS, IL-6, IL-10, and MUC2 were evaluated in the duodenum, jejunum, ileum, and colon. Results: Fear conditioning was associated with marked region-dependent alterations. Among Vehicle-treated animals, villus height was increased in the duodenum and jejunum, accompanied by enhanced immunoreactivity of several inflammation-associated markers. In contrast, the ileum and colon showed distinct profiles characterized mainly by increased IL-6, reduced selected immunoregulatory markers, and decreased MUC2. CE-123 in fear conditioning (FC) showed its clearest attenuation of inflammation-associated responses in the jejunum, where CD68, iNOS, and IL-6 immunoreactivity were reduced. In comparison, this pattern was not consistently observed in other intestinal regions: in the duodenum, only CD68 immunoreactivity was reduced, whereas in the ileum, a reduction was observed only for IL-6. In the colon, both IL-6 and CD68 showed changes in the opposite direction to those observed in the jejunum. Collectively, these region-specific and divergent responses suggest that CE-123 exerts a modulatory rather than uniformly anti-inflammatory effect on intestinal immune responses. CE-123 also produced independent effects in Control animals, including segment-specific changes in mucosal morphometry, MUC2, and selected immune markers, indicating that its actions were not limited to attenuation of conditioning-associated alterations. Conclusions: These findings demonstrate segment-specific intestinal remodeling following fear conditioning and extinction and indicate a context-dependent immunomodulatory effect of CE-123.

Myelination is a fundamental neurobiological process that enables rapid and efficient neural signal transmission, playing a key role in shaping brain connectivity and function-particularly during early development. Given the high energetic cost and tight developmental timing of myelination, disruptions in myelin formation or maintenance can increase vulnerability to genetic and environmental factors during critical periods. As such, impaired myelination and oligodendro-cyte dysfunction may contribute to the pathogenesis of various neurodevelopmental disorders (NDDs). This review synthesizes current knowledge on the role of myelin-related changes in the pathophysiology of NDDs-including Autism Spectrum Disorder (ASD), Attention-Deficit/ Hyperactivity Disorder (ADHD), Fetal Alcohol Spectrum Disorders (FASD), intellectual developmental disorders, and communication, motor, and specific learning disorders-integrating findings from both animal models and human research. Taken together, the evidence suggests that myelin-related pathways represent a common point of vulnerability across disorders and may offer a potential target for intervention.

Ketamine, originally developed as an anesthetic, is gaining increasing attention due to its multifaceted pharmacological properties. In addition to its use in anesthesia, ketamine exerts potent analgesic effects via N-methyl-D-aspartate (NMDA) receptor antagonism, modulating pain perception and reducing central sensitization, particularly in chronic and neuropathic pain conditions. Emerging evidence also supports ketamine’s potential in the treatment of substance use disorder, where it may disrupt maladaptive reward-related memories and promote neuroplasticity which facilitates behavioral change. Moreover, in recent years, S-ketamine has shown rapid and potent antidepressant effects, especially in treatment-resistant depression (TRD), probably due to increased glutamatergic signaling, synaptic plasticity and the release of neurotrophic factors. This heterogeneous therapeutic profile positions ketamine as a unique agent at the interface of anesthesia, pain management, addiction medicine and psychiatry, warranting further exploration into its mechanism and long-term effectiveness.

Glioblastoma multiforme is a highly aggressive intrinsic brain tumor with a very poor survival rate. The main treatment for cancer is surgery combined with postoperative radiotherapy and temozolomide chemotherapy. Since the outcomes of treatment are unsatisfactory, the search for more effective drugs is crucial. Our previous study indicated that mephedrone, a synthetic cathinone, reduced neuron and astrocyte viability and oligodendrocyte proliferation. The aim of the present study was to investigate the effect of mephedrone on selected human glioblastoma (LN-18, LN-229, T98G) and human anaplastic astrocytoma (MOGGCCM) cell lines. The effects of mephedrone on cell viability and proliferation, DNA synthesis, cell cycle progression and the type of cell death were studied. Our results showed that mephedrone possesses potential anticancer activity. The viability and proliferation of all four human glioblastoma and human anaplastic astrocytoma cell lines used were decreased in a concentration-dependent manner. Studies conducted on LN-18 and T98G cells confirmed the significant antiproliferative properties of mephedrone, which reduced DNA synthesis and affected cell cycle progression. Microscopic evaluation supported the antiproliferative effect of the tested compounds. Moreover, substantial cytoplasmic vacuolization in the LN-18 cell line was revealed. This finding may indicate the potential of mephedrone in anticancer therapy.

Topiramate evokes pharmacological activity via a blockade of voltage-dependent sodium channels, reduction in glutamate release, inhibition of AMPA receptors and kainate receptors, and potentiation of GABAergic neurotransmission. Therefore, it is used not only as an antiseizure drug but is also effective in migraine prophylaxis, cluster headaches, neuropathic pain, and alcohol dependence. The aim of this study was to investigate the effect of topiramate in morphine dependence in mice, particularly in terms of morphine tolerance, morphine withdrawal signs, and morphine sensitization. In these experiments, topiramate was administered both acutely and chronically. Topiramate significantly reduced the morphine tolerance in the hot-plate test and attenuated naloxone-induced morphine withdrawal signs. Its effect on morphine sensitization to the locomotor activity of mice was poor. The obtained results showed that topiramate might be an effective drug for reducing the physical symptoms of morphine dependence.

Background/Objectives: Post-traumatic stress disorder (PTSD) has been associated with negative effects on bone health, potentially leading to reduced bone mass, altered geometry, and impaired mechanical strength. However, the extent of these changes and possible pharmacological interventions remains unclear. This study aimed to assess the impact of PTSD on bone properties and evaluate the therapeutic potential of CE-123 in mitigating PTSD-induced skeletal deterioration. Additionally, we examined the effects of CE-123 on healthy bone to determine its broader influence on skeletal integrity and growth. Methods: We conducted an experiment using female Wistar rats divided into four groups: Control, PTSD, Control+CE-123, and PTSD+CE-123. PTSD was induced using a validated stress paradigm, and CE-123 was administered to evaluate its effects on bone properties. Morphometric, densitometric, and mechanical parameters of the tibia and femur were analyzed, along with growth plate measurements to assess potential effects on skeletal development. Results: PTSD led to significant reductions in bone mineral density, bone mass, and mechanical properties, particularly in cortical thickness and relative bone weight, suggesting increased bone fragility. CE-123 treatment in PTSD-exposed rats prevented some of these adverse effects but did not fully restore bone integrity. In healthy rats, CE-123 increased bone length and growth plate size, particularly in the proliferative and resting zones, indicating a stimulatory effect on bone growth. Conclusions: PTSD negatively affects bone structure and mechanical strength, while CE-123 shows a potential to mitigate these effects. However, its influence on healthy bones raises questions about its long-term impact on skeletal development. Further studies are needed to evaluate CE-123’s clinical applicability and safety, particularly in younger populations.

The N-methyl-D-aspartate (NMDA) glutamate receptor is a major target of ethanol, and it is implicated in learning and memory formation, and other cognitive functions. Glycine acts as a co-agonist for this receptor. We examined whether Org24598, a selective inhibitor of glycine transporter1 (GlyT1), affects ethanol withdrawal-induced deficits in recognition memory (Novel Object Recognition (NOR) task) and spatial memory (Barnes Maze (BM) task) in rats, and whether the NMDA receptor glycine site participates in this phenomenon. Male Wistar rats were habituated to NOR or BM tasks, and then received binge-like intragastric ethanol administration (5 days, 5 g/kg). After ethanol withdrawal, Org24598 (0.1, 0.3, and 0.6 mg/kg) was administered 30 min before NOR (day 10 of withdrawal) or the reversal learning phase of BM (day 11–13 of withdrawal) task. The expression of GluN1 and GluN2B subunits of NMDA receptors were measured in the perirhinal cortex (PRC) and hippocampus (HIP) after termination of NOR. In the BM task, a glycine antagonist, L-701,324 (5 mg/kg), was administered 30 min before Org24598 to confirm the involvement of the NMDA receptor glycine site in the effects of Org24598. Our study showed that binge-like ethanol administration induced recognition and spatial memory impairments after withdrawal in rats. Additionally, an up-regulation of GluN1 and GluN2B subunits of the NMDA receptor was observed in the HIP and PRC on day 11 of abstinence. Org24598 ameliorated memory loss and normalized the expression of these subunits. L-701,324 reversed the effect of Org24598. Thus, NMDA receptor glycine sites are important in ethanol withdrawal-induced memory impairments.

Postnatal depression is a common and severe complication of childbirth. It is an important public health problem with significant implications for both mothers and children. The exact mechanisms underlying and the factors influencing the occurrence of postnatal depression remain unclear. The literature suggests that certain dietary deficiencies during pregnancy and the postnatal period may contribute to a greater risk of maternal depression. This review focuses on the role of selenium in postnatal depression. It collects evidence from published interventional and observational studies investigating the relationship between selenium intake during the antenatal and postnatal periods and the mental status of postpartum women and summarises information about biological mechanisms that may underlie the association between selenium status and postnatal depression. The review includes studies identified through electronic searches of Medline (via PubMed) and Google Scholar databases until December 2023. Despite the small number of relevant studies and their potential methodological limitations, the findings suggest that optimizing selenium status may support the prevention and treatment of postnatal depression. Further longitudinal and interventional studies are necessary to confirm the clinical significance of these effects.

Cannabidiol (CBD), a phytocannabinoid, appeared to satisfy several criteria for a safe approach to preventing drug-taking behavior, including opioids. However, most successful preclinical and clinical results come from studies in adult males. We examined whether systemic injections of CBD (10 mg/kg, i.p.) during extinction of oxycodone (OXY, 3 mg/kg, i.p.) induced conditioned place preference (CPP) could attenuate the reinstatement of CPP brought about by OXY (1.5 mg/kg, i.p.) priming in adolescent rats of both sexes, and whether this effect is sex dependent. Accordingly, a priming dose of OXY produced reinstatement of the previously extinguished CPP in males and females. In both sexes, this effect was linked to locomotor sensitization that was blunted by CBD pretreatments. However, CBD was able to prevent the reinstatement of OXY-induced CPP only in adolescent males and this outcome was associated with an increased cannabinoid 1 receptor (CB1R) and a decreased mu opioid receptor (MOR) expression in the prefrontal cortex (PFC). The reinstatement of CCP in females was associated with a decreased MOR expression, but no changes were detected in CB1R in the hippocampus (HIP). Moreover, CBD administration during extinction significantly potentialized the reduced MOR expression in the PFC of males and showed a tendency to potentiate the reduced MOR in the HIP of females. Additionally, CBD reversed OXY-induced deficits of recognition memory only in males. These results suggest that CBD could reduce reinstatement to OXY seeking after a period of abstinence in adolescent male but not female rats. However, more investigation is required.

Linagliptin is a selective dipeptidyl peptidase-4 (DPP-4) inhibitor that indirectly elevates the glucagon-like peptide-1 (GLP-1) level. The aim of the present study was to check whether linagliptin has an influence on neurotransmission in rat brain. Rats were acutely and chronically exposed to linagliptin (10 and 20 mg/kg, intraperitoneally (i.p.)). Twenty-four hours later, the striatum and hippocampus were selected for further studies. In neurochemical experiments, using high-performance liquid chromatography with electrochemical detection (HPLC-ED), the concentrations of three major neurotransmitters—dopamine, serotonin and noradrenaline—and their metabolites were measured. The analysis of mRNA expression of dopamine (D1 and D2), serotonin (5-HT-1 and 5-HT-2) and noradrenaline (α1 and α2a) receptors was also investigated using real-time quantitative reverse transcription polymerase chain reaction (RQ-PCR) in the same brain areas. Linagliptin has the ability to influence the dopaminergic system. In the striatum, the elevation of dopamine and its metabolites was observed after repeated administration of that linagliptin, and in the hippocampus, a reduction in dopamine metabolism was demonstrated. Acute linagliptin exposure increases the serotonin level in both areas, while after chronic linagliptin administration a tendency for the mRNA expression of serotoninergic receptors (5-HT1A and 5-HT2A) to increase was observed. A single instance of exposure to linagliptin significantly modified the noradrenaline level in the striatum and intensified noradrenaline turnover in the hippocampus. The recognition of the interactions in the brain between DPP-4 inhibitors and neurotransmitters and/or receptors is a crucial step for finding novel discoveries in the pharmacology of DPP-4 inhibitors and raises hope for further applications of DPP-4 inhibitors in clinical practices.