Acta neurobiologiae experimentalis最新文献

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.

We performed a microdialysis study to examine the effects of local perfusion of COA‑Cl on the extracellular levels of dopamine (DA) and its metabolites in the dorsal striatum of mice in vivo. The mice were perfused with Ringer's solution (control) and COA‑Cl (0.05, 0.1, or 0.5 mM) into the dorsal striatum. Dialysate samples were collected every 30 min and then analyzed using high‑performance liquid chromatography coupled with an electrochemical detector. We found that local perfusion of COA‑Cl (0.1 or 0.5 mM) into the dorsal striatum of living mice produced a significant and dose‑dependent increase in extracellular levels of DA, 3‑methoxytyramine (3‑MT), and homovanillic acid (HVA), where only 0.5 mM COA‑Cl increased dihydroxyphenylacetic acid (DOPAC) levels. However, 0.05 mM of COA‑Cl did not significantly affect either DA levels or its metabolites. Then, we administered the monoamine oxidase (MAO) inhibitor clorgyline alone or in combination with COA‑Cl (0.1 mM) to test whether COA‑Cl‑induced increases in DOPAC and HVA are mediated by increased MAO activity. Clorgyline alone increased 3‑MT levels and decreased DOPAC and HVA levels but not DA levels. When combined with COA‑Cl, clorgyline increased 3‑MT levels and reversed the decrease in DOPAC and HVA levels caused by clorgyline. The increase in DA metabolism induced by COA‑Cl suggests that some DA was further metabolized into DOPAC, 3‑MT, and HVA. This indicates that COA‑Cl plays a role in DA metabolism via increased DA release and/or activation of MAO, offering new insights into the effects of COA‑Cl on DA metabolism in the brain.

Brain-derived neurotrophic factor (BDNF) is involved in the maintenance of dopamine level and the survival of dopaminergic neurons, which may affect the functionality of brain structures responsible for motor and cognitive function. The aim of the study was to assess the association of individual and combined single nucleotide polymorphism (SNP) in the rs6265 BDNF (Val66Met), rs397595 DAT (SLC6A3), and rs4680 COMT (Val158Met) genes with early‑onset of Parkinson's disease (PD) patients. Moreover, we assessed the association between the BDNF Val66Met polymorphism and the level of BDNF protein in the serum of patients with PD and controls. The study involved 163 patients with idiopathic PD divided into early onset (<55 years) and late‑onset (>55 years) groups and 91 healthy age‑matched people (Control). The SNP were determined using the TaqMan Real‑Time PCR method. Serum BDNF levels were determined by ELISA assay. The risk of developing early PD in people with the BDNF genotype AG increases threefold in comparison with the carriers of the BDNF genotype GG. In PD patients and healthy people with the BDNF genotypes AG and AA, a lower serum BDNF level was found compared to those with the BDNF genotype GG in both groups. The results of our study indicate that the presence of the Val66Met BDNF gene polymorphism is associated with reduced blood BDNF levels and an elevated risk of developing early‑onset PD. This effect appears to be more pronounced in men.

The thalamic reticular nucleus controls information processing in thalamocortical neurons. GABAergic neurons present in this nucleus express the α3 subunit of post‑synaptic GABAA receptors, which bind GABA from globus pallidus neurons. Pallidal neurons, in turn, have dopaminergic D4 receptors in their axon terminals. The thalamic reticular nucleus connects reciprocally with the thalamus, and it receives afferents from the brain cortex, as well as from other brain structures that have an important role in the modulation of the thalamic network. Based on the above, the purpose of this study was to assess the electrophysiological and molecular effects of unilateral lesion of the globus pallidus on the electric activity of the thalamic reticular nucleus. Two‑month‑old male rats were used. The right globus pallidus was lesioned with quinolinic acid. Seven days after the lesion, ipsilateral turning was registered, confirming the lesion. Afterward, electrophysiological evaluation of the right thalamic reticular nucleus' electrical activity was performed. Subsequently, mRNA expression for D4 receptors and subunit α3, as well as protein content were assessed in the right reticular nucleus. Pallidum lesion caused an increase in firing frequency and decreased firing bursts of reticular neurons. In addition, dopaminergic D4 mRNA, as well as protein increased. In contrast, GABAergic GABAA subunit α3 expression was suppressed, but protein content increased. These results show that the globus pallidus regulates firing in reticular neurons through D4 receptors and subunit α3 of GABAA receptor in the reticular nucleus of the thalamus.

Alzheimer's disease (AD) is an age‑related, progressive decline in cognitive ability. Accumulation and deposition of amyloid‑β (Aβ) is still the best‑known cause of AD that worsens over time. It is unclear whether the increase in Aβ production or the inefficiency of the degradation system causes the accumulation of β‑fibrils during AD development. This research investigated Aβ‑producing and clearance pathways in different stages of AD. For this purpose, patients were categorized into four experimental groups: patients with mild cognitive impairment, patients with moderate cognitive decline, patients with very severe cognitive decline, and healthy patients as control. Levels of Aβ‑40, soluble amyloid precursor protein beta (sAPPβ), matrix metalloproteinase‑9 (MMP‑9), matrix metalloproteinase‑3 (MMP‑3), neprilysin (NEP), angiotensin‑converting enzyme (ACE), and insulin‑degrading enzyme (IDE) were determined by ELISA kits and immunoblotting in serum samples. According to the results, the levels of Aβ‑40 and sAPPβ increased in AD patients from an early stage, and levels were maintained in progressive AD stages. MMP‑9 also increased in the early stage, but its content decreased with disease development. MMP‑3 was significantly higher in the three stages of AD compared to the control patients. However, IDE, NEP, and ACE enzymes as clearing systems decreased in all studied AD samples, with their reductions more remarkable in the middle and late stages. The results showed that multiple Aβ‑degrading enzymes such as NEP and IDE in AD patients decline as AD progresses, while Aβ‑40 and sAPPβ increased from the early stage of the disease. Therefore, it could be concluded that detection of the dementia phase is a critical step for therapeutic strategies.

The present study was assumed that N‑acetylcysteine (AC) might improve cognitive function in adolescent rats with hypothyroidism through various mechanisms. Sixty adolescent rats were randomly divided into the following groups: Vehicle (received normal saline intraperitoneally (IP)); Propylthiouracil (PTU)‑induced hypothyroidism (0.05%, dissolved in drinking water); Hypothyroid rats were IP treated with different doses of AC (50, 100, and 150 mg/kg/day) for a period of six weeks; Normal rats treated with the highest doses of AC (150 mg/kg/day). Behavioral and biochemical analyses were studied for all groups. In the Morris water maze test, AC significantly reduced both the time to find the hidden platform and the distance travelled as compared to non‑treated hypothyroid rats. In the passive avoidance test, the latency of entering the dark chamber was significantly increased by AC, whereas decreased the time spent in the darkroom of the chamber compared to the hypothyroid rats. In biochemical results, AC reduced both malondialdehyde content and nitrite while increased the thiol content, catalase and superoxide dismutase enzymes activity in both the cortex and the hippocampus, and a notable improvement in brain‑derived neurotrophic factor (BDNF) levels in hippocampal tissues of the hypothyroid rats, while decreasing the level of interleukin‑6 in rat hippocampal region. Therefore, based on the results, the beneficial effects of AC on cognitive impairment in adolescent hypothyroid rats are probably related to its anti‑oxidant properties and notable improvement in BDNF levels.

Cannabinoid and serotonin systems regulate many biological processes. The aim of the present study was to investigate the functional interaction between the cannabinoid and serotonergic systems of the primary somatosensory region (S1) of the brain in epileptiform activity caused by penicillin. The ACEA (an agonist of CB1 receptor), AM‑251 (an antagonist of CB1 receptor), 8‑OH‑DPAT (an agonist of 5‑HT1A receptor) and WAY‑100635 (an antagonist of 5‑HT1A receptor) were administered into the S1 after the same site administration of penicillin in urethane‑anesthetized rats. Electrocorticographic recording was done for a 90‑min period. The spike waves number and amplitude were recorded in 15‑min intervals. Areas under the curve (AUC) of the above‑mentioned spike alterations was calculated in 90 min. Spike waves with frequency of 30/min and amplitude of 1.3 mV were appeared after penicillin microinjection. The ACEA (50 ng), 8‑OH‑DPAT (500 ng) and ACEA (10 ng) plus 8‑OH‑DPAT (100 ng) reduced epileptiform activity. The AM‑251 (50 ng) and WAY‑100365 (500 ng) prevented the reducing effects of ACEA (50 ng) and 8‑OH‑DPAT (500 ng). The AM‑251 alone increased spike waves frequency. The AUC results supported the effects of the above‑mentioned treatments. The results showed that activating CB1 and 5‑HT1A receptors in the S1 may reduce the epileptiform activity caused by penicillin. Therefore, alone and together activation of central CB1 and 5‑HT1A receptors might be considered in the management of epilepsy treatment.

Sleep deprivation (SD) is a prevalent sleep issue in modern society that significantly impairs neurological function and quality of life in affected individuals. This study seeks to investigate the involvement of the miR‑155‑5p/BDNF axis in SD mice, aiming to establish a theoretical foundation for potential treatment strategies. Male C57BL/6 mice were utilized in the construction of a SD model using the flower pot technique. HT22 cells were selected for cellular experiments. The Morris water maze was employed to assess the learning and memory capabilities of the mice. HE staining was utilized to observe pathological changes in hippocampal tissue. Levels of IL‑1β, IL‑6, and TNF‑α were analyzed using ELISA. The expression level of miR‑155‑5p was quantified via RT‑qPCR. The binding between miR‑155‑5p and brain‑derived neurotrophic factor (BDNF) was confirmed through a dual‑luciferase reporter assay. Apoptosis of hippocampal neurons was assessed using TUNEL. Western blot analysis was conducted to evaluate the expression levels of BDNF, p65, and p‑p65. The Morris water maze test revealed that the mice exhibited prolonged escape latency, decreased swimming velocity, and reduced time spent in the target platform quadrant, which are indicative of a successful construction of the SD model. The observed cognitive deficits in the mice were associated with SD‑induced damage to the hippocampal tissue, leading to increased levels of miR‑155‑5p and decreased levels of BDNF. miR‑155‑5p was found to directly bind to BDNF, thereby suppressing its mRNA and protein expression. The upregulation of BDNF effectively mitigated hippocampal damage by attenuating cell apoptosis and reducing inflammation levels in SD mice. Additionally, the BDNF/NF‑κB pathway was found to be suppressed in SD mice through the downregulation of miR‑155‑5p. Therefore, the silencing of miR‑155‑5p inhibited the activation of the NF‑κB pathway by upregulating BDNF, which improved long‑term memory and reduced neuronal damage in SD mice.