Neurochemical Journal最新文献

Abstract

Post-stroke depressive disorders (PSD) and post-stroke cognitive impairments (PCI) are frequent consequences of ischemic stroke (IS). The study was focused on exploring possible associations between relative volumes of cortical and limbic brain structures during the acute period of IS, and changes in biochemical indices of hypothalamic-pituitary-adrenal, sympathoadrenal medullary and inflammatory systems, with the development of PSD or PCI after mild or moderate IS. Patients developing PSD later on had significantly smaller relative volumes of the hippocampus, entorhinal cortex, and temporal pole versus patients without depressive symptoms. PCI development was associated with significantly smaller volumes of temporal pole and supramarginal gyrus versus patients without cognitive changes. Multiple logistic regression analysis showed higher likelihood of developing PSD in patients with smaller temporal pole volume (β0 = 10.9; β = –4.27; p = 0.04) and in-creased salivary α-amylase activity (β0 = –3.55; β = 2.68e-05; p = 0.02). PCI likelihood was higher in patients with smaller supramarginal gyrus volume (β0 = 3.41; β = –0.99; p = 0.047), smaller temporal pole volume (β0 = 3.41; β = –3.12; p = 0. 06), and increased hair cortisol concentration at admission (index of accumulated stress load within a month before IS; β0 = 3.41; β = –0.05; p = 0.08). The data support the hypothesis suggesting predisposition to PSD and PCI and multi hit scenarios of their pathogenesis with IS providing a final hit.

Abstract—Parkinson’s disease is a chronic neurodegenerative disease, one of the pathobiochemical manifestations of which is an imbalance of neurotransmitters in the brain. The aim of this work was to study the effect of glycoalkaloids on changes in the level of neurotransmitters and markers of brain neurodegeneration in rats with experimental Parkinson’s disease. Parkinson’s disease was modeled in animals by intracerebral administration of rotenone. The studied glycoalkaloids were administered orally at a dose of 0.06 mg/kg for 28 days after pathology modeling. The study found that the use of the analyzed glycoalkaloids did not affect the concentration of dopamine and serotonin and also significantly (p < 0.05) reduced the level of ACh by 35.9% and increased the level of GABA by 55.1%, reduced the concentration of S100ß protein by 68.6%, and increased the level of BDNF by 52.4%.

Abstract

Prostaglandin D₂ is the most abundant prostaglandin in the mammalian brain. Exposure to stressful stimuli is often accompanied by reduced pain sensitivity, termed “stress-induced analgesia” (SIA). In the present study, the possible modulatory role of prostaglandin-D2 (PGD2) in the acute or chronic type of SIA was examined in male and female rats. Acute and chronic (long-term) restraint stress (RS) in male and female rats was performed prior to intraplantar injections of formalin, a noxious inflammatory agent. The involvements of specific PGD2 receptors in the modulatory role of PGD2 on SIA also investigated by specific antagonists (DP1 or DP2). Corticosterone levels were assessed in groups of rats following exposure to stress. Acute or chronic restraint stress altered formalin-induced spontaneous behaviors in male and female rats. Furthermore, intrathecal microinjection of PGD2 (10 µg/mL) could reverse acute SIA in male but not in female rats. DP2 antagonist of PGD2 (CAY10471) attenuated pain score in the acute RS-induced analgesia in male rats. Administration of PGD2 increases the phospho-extracellular signal regulated kinase 2 (pERK2) levels in the spinal cord of male RS rats. Sex differences were also seen in plasma corticosterone concentrations post injection of PGD2 in acute SIA in male rats. The outcome suggests that not only central microinjection of PGD2 could attenuate acute SIA in male rats, but also its antagonist could turn over this effect.

Abstract—The study of the status of norepinephrine-, dopamine- and serotonergic neurotransmitter systems of BALB/C mice brain structures on 15 and 64 days of postnatal development (PD) in the model of autistic disturbances induced by injection of sodium valproate (SV, 400 mg/kg , s/c) to pregnant females was carried out using the HPLC/ED method. The level of both catechol- and indolamines in the brain structures of control mice at the age of 15 days was significantly lower than in adult animals at the age of 64 days. Prenatal administration of SV caused a decrease in all parameters of monoaminergic neurotransmission in the striatum of offspring at the age of 15 days but had no effect in other brain structures studied. Subsequently, the level of dopamine increased and by the 64th day of PD did not differ from the parameters of the control group. The parameters of the serotonergic system changed in a similar pattern, with the content of serotonin and the serotonin metabolite 5-OIAA in the striatum increasing gradually and reaching maximum values by the 64th day of PD. Our data allows to assume that the administration of SV to pregnant females affects the activity of the dopamine and serotonergic systems of the brain of the offspring causing a decrease in their activity in the striatum by the 15th day of PD followed by restoration to control values by the 64th day, which we previously observed in male pups. Thus, the patterns of dynamic changes in the neurochemical profile do not differ between males and females.

Abstract

Chronic administration of morphine causes physical dependence, possibly through serotonin 5‑HT_1A receptor (5-HT_1AR) and 5-HT_2A receptor (5-HT_1AR). The aim of this study was to evaluate the effect of 5-HT_1AR antagonist, NAD 299 hydrochloride (NAD 299), and 5-HT_2A R agonist (TCB-2) on the withdrawal syndrome in morphine-dependent mice. Adult male mice were randomly divided into five groups. Three groups of mice were treated with NAD-299 (0.3 mg/kg, i.p.) and TCB-2 (0.3 mg/kg, i.p.) 15 min before naloxone injection (3 mg/kg, s.c.) to investigate the effect of the 5-HT_1AR antagonist and 5-HT_2AR agonist on morphine withdrawal syndrome. Morphine was administered subcutaneously with increasing daily doses at 12-h intervals for five days to induce dependence. The withdrawal symptoms, including jumping, abdomen writhing, body weight loss, and head shakes, were recorded for 30 min. Cortisol and total antioxidant levels were assessed 2 h after the morphine withdrawal test. There was a reduction in total withdrawal score and an increase in head shakes and total antioxidant capacity in the NAD-299 + morphine group compared to the morphine group. The TCB-2 + morphine group exhibited an increase in jumping and a decrease in writhing, head shakes, and withdrawal score compared to the morphine group. The NAD-299 + TCB-2 + morphine group showed a decrease in the number of jumping and total withdrawal score, and an increase in the head shakes and cortisol levels compared to the morphine group. The combined treatment with NAD-299 and TCB-2 modulates the morphine withdrawal syndrome and increases cortisol levels.

Abstract

Epileptic seizures are caused by abnormal neuronal excitation. It is well established that carvacrol, a monoterpenoid phenol, is able to inhibit the voltage-gated sodium channels and L-type Ca²⁺ channels and enhance activation of GABA(A) receptors. We therefore hypothesize that carvacrol may prevent epileptic seizures by inhibiting neuronal cation influx and facilitating anion influx. Herein, we investigated possible anti-convulsant effects of carvacrol on penicillin-induced epileptiform activity and pentylenetetrazole (PTZ)-induced seizures in rats. 63 male Wistar rats were assigned to the penicillin- and the pentylenetetrazole-induced groups. Both subgroups received three different doses of carvacrol (25, 75, and 150 mg/kg) intraperitoneally. Seizure stage, onset-times of both myoclonic-jerk and generalized tonic-clonic seizures and the duration of generalized tonic-clonic seizure were evaluated using Racine’s scale in PTZ group, while spike frequency and the amplitude of epileptiform discharges were evaluated in the penicillin-induced group. The administration of carvacrol significantly extended the onset time of the first myoclonic jerk (150 mg/kg, p = 0.019) and decreased the number of spike-waves (75 mg/kg, p = 0.033). This study showed that carvacrol has the anti-convulsant effect. However, this effect was observed at a low level. The limited the anti-convulsant effect of carvacrol may be due to its insufficient of acute effect related to the transition of carvacrol to the epileptic focus. More studies are needed to evaluate the effect of carvacrol on chronic epilepsy models and its molecular and pharmacokinetic mechanisms.

Abstract

Sugammadex (SUG) is a modified γ-cyclodextrin molecule used in patients under general anesthesia to reverse the effects of neuromuscular blocking agents. Besides, recent studies have shown that SUG positively affects the nervous system. However, its effect on seizures is still unclear. The current study aimed to examine the effects of SUG on pentylenetetrazole (PTZ)-induced epileptic seizures in mice. The mice were randomly divided into four groups. Group 1 was controlled, group 2 was administered saline (1 mL/kg serum physiologic), and Groups 3 and 4 were administered Sugammadex (150 and 300 mg/kg). Pentylenetetrazole (60 mg/kg) was given to induce seizures 30 min after saline or drug administration except for the control group. Total oxidant status (TOS) and total antioxidant status (TAS) levels in the hippocampus and cortex were measured using a commercial kit. 8-hydroxydeoxyguanosine (8-OHdG), 4-hydroxynonenal (4‑HNE), 3,3 dityrosine, caspase-3, apoptosis-inducing factor (AIF), and light chain 3 (LC3B) levels in the hippocampal CA1 region and cortex after seizures were evaluated immunohistochemical staining. SUG reduced seizure stages and increased epileptic seizure onset times. Moreover, it decreased TOS levels and increased TAS levels in the hippocampus and cortex. Besides, after seizures, it reduced 4-HNE, 3,3 dityrosandine, caspase-3, and LC3B immunohistochemical scores in the hippocampal CA1 region and cortex. SUG has protective effects on pentylenetetrazole-induced seizures in mice, alleviating seizures, oxidative stress, apoptosis, and autophagy. The anticonvulsant mechanism of SUG may be related to the inhibition of the oxidative stress pathway.

Abstract

This study aims to compare the clinical efficacy of coblation tonsillectomy with that of conventional tonsillectomy for the treatment of chronic tonsillitis (CT). The clinical data of 87 patients with CT treated in our hospital from November 2020 to October 2022 were retrospectively analyzed, and patients were divided into two groups based on the surgical protocol. Among them, 43 patients treated with traditional tonsillectomy were set as control group, and 44 patients treated with coblation tonsillectomy were set as study group. We compared perioperative indexes, serum stress indicators (PCT, Cor, PGE2, PGF2α), inflammatory mediator levels (CRP, TNF-α, WBC, NLR), pain level (VAS score), immune function (T lymphocyte subpopulation) at different time points, and complications between the two groups. The study group had significantly lower intraoperative bleeding, shorter operation time, feeding and hospitalization time, and longer time for complete regression of yellow-white scabs than the control group (P < 0.05). At 1 day postoperatively, the study group had significantly lower levels of serum PCT, Cor, CRP, TNF-α, WBC, and NLR than the control group, while PGE2 and PGF2α levels decreased in both groups (P < 0.05). At 1, 3, 5, and 7 day after surgery, the VAS scores were significantly lower in the study group than in the control group (P < 0.05). At 1 week after surgery, the study group had significantly higher levels of CD3+, CD4+, and CD4+/CD8+ and significantly lower levels of CD8+ than the control group (P < 0.05). The complication rate in the study group (4.55%) was significantly lower than that in the control group (20.93%) (P < 0.05). Coblation tonsillectomy is less traumatic for CT patients, effectively reduces the degree of postoperative pain, decreases stress response, suppresses inflammatory response, improves immune function, reduces complications, and promotes postoperative recovery compared with traditional tonsillectomy.

Abstract

Extracellular adenosine 5′-triphosphate (ATP), as neurotransmitter, is known to be an activity-dependent signaling molecule that regulates synaptic signaling. It is known to be co-released with acetylcholine from synaptic vesicle. The P2Y2 receptor (P2Y2R) is present in gastrocnemius muscles and co-localizes with post-synaptic acetylcholine receptors (AChRs). Accumulating evidence indicates that P2Y2R plays crucial roles in assembling neuromuscular junctions (NMJs), a peripheral synapse characterized by the clustering of AChRs on post-synaptic densities. This study investigated the alterations in P2Y2R expression during muscle reinnervation and the effect on NMJ formation. We found that P2Y2R consistently co-localized with AChR and sustained high expression in post-synaptic regions during muscle reinnervation. Notably, PSB1114-dependent stimulation of P2Y2R promoted NMJ formation and muscle reinnervation. The stimulatory effect of PSB1114 was significantly blocked by administration of the P2Y2R antagonist suramin. This study revealed distinctive patterns of expression and localization and a potential role of P2Y2R in promoting NMJ formation and regeneration during skeletal muscle reinnervation.

Abstract—Here we studied the effects of anti-epileptic substance GIZh-298 and the drug of comparison sodium valproate (NaV) on the contents of excitatory and inhibitory amino acids in the frontal cortex, hypothalamus, striatum, and hippocampus of the mouse brain in a model of generalized tonic-clonic seizures induced by maximal electroshock (MES). The levels of excitatory amino acids such as aspartate in the hypothalamus and glutamate in the hippocampus were decreased by 20.8 and 16.7%, respectively, and of inhibitory amino acids, such as glycine, GABA, and taurine were also decreased by 16–20% in average in those structures 5 min after the MES application indicating the exhaustion of aminoacidic neurotransmission. Intragastric administration of NaV at a dose of 200 mg/kg, which causes the anti-seizure effect, prevented the MES-induced decrease in the content of GABA and the GABA/glutamate ratio in the hypothalamus. NaV similarly decreased the aspartate level in the hypothalamus, striatum, and hippocampus in the intact group of mice and in mice after seizures. Intragastric administration of GIZh-298 at a dose of 60 mg/kg prevented the MES-evoked decrease in the GABA/glutamate ratio and the levels of GABA, glycine, and taurine in the hypothalamus.