Acta neurobiologiae experimentalis最新文献

The article provides a review of the sensory processing (SP) phenomenon, its origins, theoretical models, and neurophysiological foundations. Initiated by A. Jean Ayres' research on sensory integration in the 1960s and 70s, this field has evolved, leading to the development of concepts such as Winnie Dunn's four quadrant model and Miller's ecological model of sensory modulation. Over the years, based on theoretical considerations, the concepts of sensory processing disorder and sensory processing sensitivity were formulated. The article highlights the role of temperament and its impact on sensory processing, suggesting that individual differences can significantly affect how people respond to sensory stimuli. The neurophysiological basis including sensory gating, electrodermal responses, and neuroimaging methods is presented. There has been an interest in the relationship between SP and mental disorders in adults, despite the lack of a formal diagnosis in DSM‑5 and ICD classifications. The literature analysis reveals the complexity of the subject, indicating the need for further research in this field.

Piperine is an amide alkaloid isolated from the black pepper plant. This study examined the pain‑relieving activity of piperine against paclitaxel (PTX)‑induced neuropathy. Male mice were divided into 6 groups: Sham‑operated group (remained intact), PTX group (PTX‑treated mice receiving normal saline), PTX+ piperine 10, 25, and 50 mg/kg groups (PTX‑treated mice receiving piperine) and positive control group (PTX‑treated mice receiving imipramine 10 mg/kg). Neuropathic pain was induced by PTX 2 mg/kg/day on days 1, 3, 5 and 7. On day 7, behavioral tests were conducted and serum levels of interleukin‑6 (IL‑6), tumor necrosis factor‑alpha (TNF‑α), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) were assayed. PTX produced significant thermal hyperalgesia compared to the sham group. Piperine at all doses alleviated neuropathic pain, and significantly decreased IL‑6, TNF‑α, and MDA, but induced CAT and SOD activities compared to the control group. Piperine could confer beneficial effects against neuropathic pain, at least partially, via reduction of inflammatory and oxidative stress markers.

Neuroinflammation and the immune response are recognized as significant mechanisms contributing to the progression and pathophysiology of Parkinson's disease (PD). Consequently, extensive research is being conducted on drugs targeting inflammation and immune response. Leflunomide, known for its anti‑inflammatory and immunomodulatory properties, is currently used as a disease‑modifying agent for the treatment of rheumatoid arthritis. The objective of this study was to investigate the effect of leflunomide on PD. The PD model was established by administering 18 mg/kg of 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine (MPTP) intraperitoneally for 5 consecutive days. Leflunomide was administered intraperitoneally at doses of 1, 5, and 10 mg/kg for 14 days. Motor and behavioral deficits were assessed using the rotarod test, locomotor activity assessment, hanging wire test, and pole test. MPTP administration impaired motor function and locomotor activity, and caused muscle weakness and bradykinesia. Leflunomide at a dose of 10 mg/kg mitigated the severity of motor deficits and muscle weakness. Furthermore, leflunomide at a dose of 10 mg/kg suppressed the MPTP‑induced elevation of interleukin‑2, interleukin‑6, and tumor necrosis factor‑alpha levels in the brain tissue. Similarly, leflunomide attenuated the increased expression of nuclear factor kappa B and inducible nitric oxide synthase caused by MPTP treatment. Moreover, leflunomide at a dose of 10 mg/kg preserved neuronal integrity and prevented the loss of tyrosine hydroxylase expression induced by MPTP administration. Based on our findings, leflunomide exhibited a beneficial effect on the MPTP‑induced PD model, potentially through modulation of anti‑inflammatory mechanisms.

The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene is a critical tumor suppressor that plays an essential role in the development and functionality of the central nervous system. Located on chromosome 10 in humans and chromosome 19 in mice, PTEN encodes a protein that regulates cellular processes such as division, proliferation, growth, and survival by antagonizing the PI3K‑Akt‑mTOR signaling pathway. In neurons, PTEN dephosphorylates phosphatidylinositol‑3,4,5‑trisphosphate (PIP3) to PIP2, thereby modulating key signaling cascades involved in neurogenesis, neuronal migration, and synaptic plasticity. PTEN is crucial for embryonic neurogenesis, controlling the proliferation of neural progenitor cells and guiding the migration and proper lamination of neurons in cortical and hippocampal structures. It also regulates dendritic growth and axon guidance, ensuring correct neuronal connectivity. In postnatal neurogenesis, PTEN maintains the balance of stem cell proliferation and integration of new neurons into existing circuits, particularly in the hippocampal dentate gyrus. Animal models with PTEN deletion or mutation exhibit significant structural and functional neuronal abnormalities, including enlarged soma and dendritic hypertrophy, increased synaptic density, and altered synaptic plasticity mechanisms such as long‑term potentiation and long‑term depression. These changes lead to deficits in learning and memory tasks, as well as impairments in social behaviors. PTEN mutations are associated with neurodevelopmental disorders like intellectual disability, epilepsy, and autism spectrum disorders accompanied by macrocephaly. Understanding PTEN's mechanisms offers valuable insights into its contributions to neurodevelopmental disorders and presents potential therapeutic targets for cognitive impairments and neurodegenerative diseases. Future research should focus on elucidating PTEN's functions in mature neurons and its influence on established neuronal networks, which may have significant implications for memory enhancement and behavioral modifications.

Autism spectrum disorder (ASD) is among the most common neurodevelopmental conditions in humans. While public awareness of the challenges faced by individuals with autism is steadily increasing, the underlying causes of abnormalities observed in ASD remains incompletely understood. The autism spectrum is notably broad, with symptoms that can manifest in various forms and degrees of severity. Core features of ASD, such as communication difficulties, impaired social interactions, and restricted patterns of behavior, interests, and activities, are often accompanied by other co‑occurring conditions, such as anxiety. ASD affects individuals regardless of gender, race, or ethnicity. Although we are currently unable to pinpoint a single definitive cause of autism, it is clear that genetics play a crucial role in its development. The first genes associated with an increased risk for ASD were discovered in rare monogenic disorders, such as fragile X syndrome (FXS), caused by mutations in the fragile X messenger ribonucleoprotein 1 (FMR1) gene, and macrocephaly, linked to mutations in the phosphatase and tensin homolog (PTEN) gene. This review aims to summarize the current knowledge of ASD in patients with mutations in the FMR1 and PTEN genes.

In recent years, growing evidence suggests that lipopolysaccharide (LPS), a bacterial endotoxin found in the outer membrane of gram‑negative bacteria, can influence cognitive functions, particularly memory formation and retrieval. However, the underlying mechanisms through which LPS exerts its effects on memory remain incompletely understood. This review used various electronic databases, including PubMed, Scopus, and Web of Science, to identify relevant studies published between 2000 and 2024. Articles were selected based on their focus on LPS‑induced memory impairments, including experimental models, molecular pathways, and neurochemical alterations. LPS administration has been consistently shown to disrupt memory processes in both animals and humans, although the magnitude and duration of memory impairments might vary depending on factors such as dose, timing, and context of LPS exposure. Several potential mechanisms have been proposed to explain LPS‑induced memory deficits, including neuroinflammation, alterations in synaptic plasticity, disruption of neurotransmitter systems, and dysfunction of the blood‑brain barrier. Moreover, LPS has been found to activate immune signaling pathways, such as toll‑like receptors, interleukins, and microglia, which can further contribute to cognitive impairments. Such insights may pave the way for the development of targeted therapeutic interventions aimed at ameliorating memory deficits associated with conditions involving LPS exposure, including bacterial infections, sepsis, and neuroinflammatory disorders.

MicroRNA‑regulated gene expression plays an important role in autoimmune diseases, such as multiple sclerosis (MS). This study investigated the expression patterns of microRNAs (miRNAs) in MS in brain tissues using an animal experimental autoimmune encephalomyelitis (EAE) model treated with Hypericum perforatum (HP) oil. C57BL/6 J mice were divided into two groups: MS and control. The MS group was subdivided into sham (MS) and MS+HP. After the EAE induction treatment protocol, the patterns of miRNA expression profiles were determined in brain samples of the groups. The array data identified eleven miRNAs and candidate miRNA validation was performed by RT‑qPCR. A literature review of the validated miRNAs found that six of the eleven miRNAs (miR‑200a‑3p, miR‑200b‑3p, miR‑200c‑3p, miR‑182‑5p, miR‑183‑5p, and miR‑1298‑5p) were directly associated with MS. These miRNAs have been suggested as biomarkers of MS because they are highly correlated with the pathology of the disease. Furthermore, miRNA array analysis identified five candidate miRNAs (miR‑299a‑5p, miR‑206‑3p, miR‑325‑5p, miR‑10b‑5p, miR‑429‑3p) that are highly likely to be associated with MS pathogenesis, which could be helpful in the diagnosis and treatment of MS disease. This research offers vital insights that could be utilized in creating biomarkers and advancing treatments for MS.

Evidence is provided that the glycosylated flavonoid vitexin (apigenin‑8‑C‑beta‑D‑glucopyranoside) attenuates pentylenetetrazole (PTZ)‑induced acute tonic‑clonic seizures in rats. However, the effects of chronic and systemic vitexin in PTZ‑kindled rats remain unknown. The aim of this work was to investigate the effect of long‑term treatment with vitexin in the PTZ‑kindling model of epilepsy. Male Wistar rats received intraperitoneal injections of PTZ at a subconvulsive dose of 35 mg/kg every other day for 29 days. Either saline containing dimethyl sulfoxide - DMSO 1%  (vehicle), diazepam (2 mg/kg; positive control) or vitexin (2.5 mg/kg) was administered intraperitoneally 30 min before each PTZ injection. The behavioral reactions were recorded by 30 min immediately after each PTZ injection. Furthermore, on the 31st day, that is, 48 h after the latter dose of PTZ, the animals were euthanized and renal and hepatic biochemical markers were evaluated in blood serum. Chronic treatment with either diazepam or vitexin attenuated the seizures provoked by PTZ injections. Neither diazepam nor vitexin caused changes in renal levels of creatinine and urea and in hepatic levels of aspartate aminotransferase and alanine aminotransferase. Our findings suggest that chronic administration of vitexin attenuates the progression of PTZ‑induced kindling without causing side effects on kidneys and liver.

Obsessive‑compulsive disorder (OCD) is a current topic of discussion nowadays. OCD presents a variety of different etiologies including environmental, viral, cognitive, or genetic aspects. In this article, we focused on the possible correlation between various infectious diseases as well as generally the relationship between viruses, bacteria, and parasites, and an increased OCD risk. In this narrative review, we analyzed different types of articles found on PubMed, Google Scholar, and Scopus, as well as the articles of the National Institute of Mental Health. Searching criteria included articles from 1991 till the end of November, research involving human and animal patients (including monkeys and rats), and research published in English. Research showed a relationship between Herpes simplex virus, Rubella virus, Human immunodeficiency virus, Borna disease virus, Mycoplasma pneumoniae, Toxoplasma gondii, streptococcal infections, as well as gut microbiota and increased OCD risk. The possible mechanisms of this relation include neuroinflammation, brain tissue damage, autoimmune processes, and impairments in neurotransmitter levels. Infections caused by Varicella zoster virus, Measles virus, Mumps virus, Epstein‑Barr virus, Cytomegalovirus, or Borrelia Burgdorferi may also contribute to the increased risk of OCD. Reports showed an increased frequency of OCD occurrence in a group of infected people compared to a healthy group. However, there is no evidence of the influence of Influenza virus, Coxsackie virus, Poliovirus, Parvovirus B19, Enterovirus 71, West Nile virus, Treponema Pallidum, or Toxocara infections on the OCD risk. There is a significant relationship between various infectious diseases and an increased OCD risk. However, further studies are crucial to discover the exact pathomechanisms of these correlations and the potential influence of other pathogens on the onset of OCD.

Phenylketonuria (PKU) stems from a rare genetic metabolic imbalance attributed to an insufficiency in the enzyme phenylalanine hydroxylase. Within the context of PKU, brain‑derived neurotrophic factor (BDNF) plays a pivotal role in brain function. 7,8‑dihydroxyflavone (7,8‑DHF) operates as a tropomyosin receptor kinase B (TrkB) agonist, mimicking the effects of BDNF. This study aimed to examine the effects of administering 7,8‑DHF in chemically‑induced rat models specifically induced to simulate PKU chemically. The rats were subcutaneously injected with phenylalanine and p‑chlorophenylalanine, a phenylalanine hydroxylase inhibitor, along with 7,8‑DHF. The injections began on the 2nd day after birth and continued until the 10th day. Levels of interleukin‑1β (IL‑1β), interleukin‑6 (IL‑6), interleukin‑33 (IL‑33), BDNF, malondialdehyde (MDA), monoamine oxidase (MAO), and superoxide dismutase (SOD) in the brain tissues were quantified using the enzyme‑linked immunosorbent assay (ELISA). Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was performed to assess the gene expressions of inducible nitric oxide synthase (iNOS), nuclear factor kappa beta (NF‑κB), caspase‑3, nuclear factor erythroid 2‑related factor 2 (Nrf2), heme oxygenase‑1 (HO‑1), and BDNF. The results showed a decrease in mRNA levels of iNOS, IL‑1β, IL‑6, and lipid peroxidation in the group that received 7,8‑DHF. These results indicate that administering 7,8‑DHF has the potential to reduce brain damage in PKU by lowering proinflammatory cytokine levels and lipid peroxidation in PKU models. Thus, 7,8‑DHF, as a small molecule, might offer a promising adjunct therapeutic approach for PKU.