Abstract In clinical practice, depression and anxiety frequently coexist, and they are both comorbid with somatic diseases. The P2X7R is an adenosine 5’-triphosphate (ATP)-gated non-selective cation channel that is widely expressed in immune-related cells. Under conditions of stress, chronic pain, and comorbid chronic physical illness, P2X7R activation in glial cells leads to neuroinflammation. This could contribute to the development of anxiety and depression-related emotional disturbances. Previous studies have shown that the P2X7 receptor (P2X7R) plays an important role in the pathogenesis of both anxiety and depression. Thus, the P2X7R may play a role in the comorbidity of anxiety and depression. Positron emission tomography can be used to assess the degree and location of neuroinflammation by monitoring functional and expression-related changes in P2X7R, which can facilitate clinical diagnoses and guide the treatment of patients with anxiety and depression. Moreover, single nucleotide polymorphisms (SNPs) in the P2X7R gene are associated with susceptibility to different types of psychiatric disorders. Thus, evaluating the SNPs of the P2X7R gene could enable personalized mood disorder diagnoses and treatments. If the P2X7R were set as a therapeutic target, selective P2X7R antagonists may modulate P2X7R function, thereby altering the balance of intra- and extra-cellular ATP. This could have therapeutic implications for treating anxiety and depression, as well as for pain management. According to in vitro and in vivo studies, the P2X7R plays an important role in anxiety and depression. In this review, we consider the potential of the P2X7R as a therapeutic target for comorbid anxiety and depression, and discuss the potential diagnostic and therapeutic value of this receptor.
There lacks biomarkers in current epilepsy diagnosis, and epilepsy is thus exposed to inadequate treatment, making it necessarily important to conduct search on new biomarkers and drug targets. The P2Y12 receptor is primarily expressed on microglia in the central nervous system, and acts as intrinsic immune cells in the central nervous system mediating neuroinflammation. In previous studies, P2Y12R in epilepsy has been found capable of controlling neuroinflammation and regulating neurogenesis as well as immature neuronal projections, and its expression is altered. P2Y12R is involved in microglia inhibition of neuronal activity and timely termination of seizures in acute seizures. In status epilepticus, the failure of P2Y12R in the process of “brake buffering” may not terminate the neuronal hyperexcitability timely. In chronic epilepsy, neuroinflammation causes seizures, which can in turn induce neuroinflammation, while on the other hand, neuroinflammation leads to neurogenesis, thereby causing abnormal neuronal discharges that give rise to seizures. In this case, targeting P2Y12R may be a novel strategy for the treatment of epilepsy. The detection of P2Y12R and its expression changes can contribute to the diagnosis of epilepsy. Meanwhile, the P2Y12R single-nucleotide polymorphism is associated with epilepsy susceptibility and endowed with the potential to individualize epilepsy diagnosis. To this end, functions of P2Y12R in the central nervous system were hereby reviewed, the effects of P2Y12R in epilepsy were explored, and the potential of P2Y12R in the diagnosis and treatment of epilepsy was further demonstrated.
Abstract Objective To investigate and analyze the etiology and prognosis of patients with new‐onset status epilepticus (NOSE). Methods We conducted a retrospective analysis of all adult patients (≧16 years old) who were admitted to Sichuan Provincial People's Hospital between January 2018 and December 2020 with status epilepticus (SE) and no prior epilepsy history. Results We collected data from 85 patients, aged from 16 to 90 years, of whom 49 were male and 36 were female. Fifty‐five of these cases (64.7%) were younger than 60 years of age. Acute symptomatic SE was mostly seen in the NOSE (53.9%), followed by unknown SE (25.9%), progressive SE (11.8%), and remote SE (9.4%). The differences in the etiology of NOSE between age groups were statistically significant ( P < .05). For the young, the main etiology remained unknown (36.3%), followed by autoimmune‐related SE (16.4%); in the elderly, the primary etiology was central nervous system (CNS) infection (23.3%), followed by cerebrovascular disease (20%), and intracranial tumors (20%). Normal imaging was mostly seen in young people with NOSE ( P < .001). Regarding outcome parameters and risk factors in patients with NOSE, adverse outcome was associated with age (OR = 3.5, 95% CI = 0.108–0.758, P = .012), co‐infection (OR = 4.5, 95% CI = 0.083–0.599, P = .003), and tracheal intubation (OR = 6.318, 95% CI = 0.060–0.204, P = .011). Significance In our cohort, intracranial tumors, CNS infections, and cerebrovascular disease were the predominant causes of NOSE in the elderly, while autoimmune encephalitis was the largest recognized cause of NOSE in young patients. In addition, imaging varies with age. According to the data, preventing infections may enhance patient prognosis because greater infection rates are connected with less favorable results. Meanwhile, age and mechanical ventilation are related to the prognosis of NOSE.
Abstract The basic research indicated that microglial P2Y12 receptors ( P2Y12Rs ) are involved in the pathophysiology of epilepsy through regulated microglial-neuronal interactions, aberrant neurogenesis, or immature neuronal projections. However, whether the clinic case of epilepsy would be associated with P2Y12 receptor gene polymorphisms is presented with few data. In our study, a total of 176 patients with epilepsy and 50 healthy controls were enrolled. Two single-nucleotide polymorphisms, namely rs1491974 and rs6798347, were selected for analysis. The results revealed that carriers of the G allele of rs1491974 G>A or rs6798347 G>A may be associated with an increased risk of epilepsy (OR = 0.576, 95% CI = 0.368–0.901, p = 0.015; OR = 0.603, 95% CI = 0.367–0.988, p = 0.043). Interestingly, we found that the rs1491974 G>A genotype and allele frequencies have only a significant difference in female instead of male case ( p = 0.004 for genotype; p = 0.001 for allele). The subgroup analysis demonstrated that individuals with the rs1491974 G>A genotype might have more frequent seizure (OR = 0.476, 95% CI = 0.255–0.890; p = 0.019). These data implied that both rs1491974 and rs6798347 polymorphisms of P2Y12R would be able to play import roles in epilepsy susceptibility, whereas the rs1491974 polymorphism may be specifically related to seizure frequency.
Single-nucleotide polymorphisms are connected with the risk of epilepsy on occurrence, progress, and the individual response to drugs. Progress in genomic technology is exposing the complex genetic architecture of epilepsy. Compelling evidence has demonstrated that purines and adenosine are key mediators in the epileptic process. Our previous study found the interconnection of P2Y12 receptor single-nucleotide polymorphisms and epilepsy. However, little is known about the interaction between the purine nucleoside A2A receptor and rate-limiting enzyme ecto-5'-nucleotidase/CD73 and epilepsy from the genetic polymorphism aspect. The aim of the study is to evaluate the impact of A2AR and CD73 polymorphisms on epilepsy cases. The study group encompassed 181 patients with epilepsy and 55 healthy volunteers. A significant correlation was confirmed between CD73 rs4431401 and epilepsy (p < 0.001), with TT genotype frequency being higher and C allele being lower among epilepsy patients in comparison with healthy individuals, indicating that the presence of the TT genotype is related to an increased risk of epilepsy (OR = 2.742, p = 0.006) while carriers of the C allele demonstrated a decreased risk of epilepsy (OR = 0.304, p < 0.001). According to analysis based on gender, the allele and genotype of rs4431401 in CD73 were associated with both male and female cases (p < 0.0001, p = 0.026, respectively). Of note, we found that A2AR genetic variants rs2267076 T>C (p = 0.031), rs2298383 C>T (p = 0.045), rs4822492 T>G (p = 0.034), and rs4822489 T>G (p = 0.029) were only associated with epilepsy in female subjects instead of male. It is evident that the TT genotype and T allele of rs4431401 in CD73 were genetic risk factors for epilepsy, whereas rs2267076, rs2298383, rs4822492, and rs4822489 polymorphisms of the A2AR were mainly associated with female subjects.
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