scholarly journals Chronic presence of blood circulating anti-NMDAR1 autoantibodies impairs cognitive function in mice

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0256972
Author(s):  
William Yue ◽  
Sorana Caldwell ◽  
Victoria Risbrough ◽  
Susan Powell ◽  
Xianjin Zhou
Keyword(s):  
Cognitive Functions ◽  
Human Population ◽  
Spatial Working Memory ◽  
Psychiatric Symptoms ◽  
Psychiatric Patients ◽  
Novelty Detection ◽  
Sensorimotor Gating ◽  
Healthy Human ◽  
Blood Brain ◽  
Brain Barriers

High titers of anti-NMDAR1 autoantibodies in brain cause anti-NMDAR1 encephalitis that displays psychiatric symptoms of schizophrenia and/or other psychiatric disorders in addition to neurological symptoms. Low titers of anti-NMDAR1 autoantibodies are reported in the blood of a subset of the general human population and psychiatric patients. Since ~0.1–0.2% of blood circulating antibodies cross the blood-brain barriers and antibodies can persist for months and years in human blood, it is important to investigate whether chronic presence of these blood circulating anti-NMDAR1 autoantibodies may impair human cognitive functions and contribute to the development of psychiatric symptoms. Here, we generated mice carrying low titers of anti-NMDAR1 autoantibodies in blood against a single antigenic epitope of mouse NMDAR1. Mice carrying the anti-NMDAR1 autoantibodies are healthy and display no differences in locomotion, sensorimotor gating, and contextual memory compared to controls. Chronic presence of the blood circulating anti-NMDAR1 autoantibodies, however, is sufficient to impair T-maze spontaneous alternation in the integrity of blood-brain barriers across all 3 independent mouse cohorts, indicating a robust cognitive deficit in spatial working memory and/or novelty detection. Our studies implicate that chronic presence of low titers of blood circulating anti-NMDAR1 autoantibodies may impair cognitive functions in both the general healthy human population and psychiatric patients.

scholarly journals Chronic Presence of Blood Circulating Anti-NMDAR1 Autoantibodies Impairs Cognitive Function in Mice

2021 ◽  
Author(s):  
William Yue ◽  
Sorana Caldwell ◽  
Victoria Risbrough ◽  
Susan Powell ◽  
Xianjin Zhou
Keyword(s):  
Cognitive Functions ◽  
Human Population ◽  
Spatial Working Memory ◽  
Psychiatric Symptoms ◽  
Psychiatric Patients ◽  
Novelty Detection ◽  
Sensorimotor Gating ◽  
Healthy Human ◽  
Blood Brain ◽  
Brain Barriers

AbstractHigh titers of anti-NMDAR1 autoantibodies in brain cause anti-NMDAR1 encephalitis that displays psychiatric symptoms of schizophrenia and/or other psychiatric disorders in addition to neurological symptoms. Low titers of anti-NMDAR1 autoantibodies are reported in the blood of a subset of the general human population and psychiatric patients. Since ∼0.1-0.2% of blood circulating antibodies cross the blood-brain barriers and antibodies can persist for months and years in human blood, it is important to investigate whether chronic presence of these blood circulating anti- NMDAR1 autoantibodies may impair human cognitive functions and contribute to the development of psychiatric symptoms. Here, we generated mice carrying low titers of anti-NMDAR1 autoantibodies in blood against a single antigenic epitope of mouse NMDAR1. Mice carrying the anti-NMDAR1 autoantibodies are healthy and display no differences in locomotion, sensorimotor gating, and contextual memory compared to controls. Chronic presence of the blood circulating anti-NMDAR1 autoantibodies, however, is sufficient to specifically impair T-maze spontaneous alternation in the integrity of blood-brain barriers across all 3 independent mouse cohorts, indicating a robust cognitive deficit in spatial working memory and/or novelty detection. Our studies implicate that chronic presence of low titers of blood circulating anti-NMDAR1 autoantibodies may impair cognitive functions in both the general healthy human population and psychiatric patients.

scholarly journals Transfer of rhodamine-123 into the brain and cerebrospinal fluid of fetal, neonatal and adult rats

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Liam M. Koehn ◽  
Katarzyna M. Dziegielewska ◽  
Mark D. Habgood ◽  
Yifan Huang ◽  
Norman R. Saunders
Keyword(s):  
Cerebrospinal Fluid ◽  
Fetal Brain ◽  
Maternal Blood ◽  
Adult Brain ◽  
Rhodamine 123 ◽  
Patient Specific ◽  
Adult Rats ◽  
Blood Brain ◽  
The Brain ◽  
Brain Barriers

Abstract Background Adenosine triphosphate binding cassette transporters such as P-glycoprotein (PGP) play an important role in drug pharmacokinetics by actively effluxing their substrates at barrier interfaces, including the blood-brain, blood-cerebrospinal fluid (CSF) and placental barriers. For a molecule to access the brain during fetal stages it must bypass efflux transporters at both the placental barrier and brain barriers themselves. Following birth, placental protection is no longer present and brain barriers remain the major line of defense. Understanding developmental differences that exist in the transfer of PGP substrates into the brain is important for ensuring that medication regimes are safe and appropriate for all patients. Methods In the present study PGP substrate rhodamine-123 (R123) was injected intraperitoneally into E19 dams, postnatal (P4, P14) and adult rats. Naturally fluorescent properties of R123 were utilized to measure its concentration in blood-plasma, CSF and brain by spectrofluorimetry (Clariostar). Statistical differences in R123 transfer (concentration ratios between tissue and plasma ratios) were determined using Kruskal-Wallis tests with Dunn’s corrections. Results Following maternal injection the transfer of R123 across the E19 placenta from maternal blood to fetal blood was around 20 %. Of the R123 that reached fetal circulation 43 % transferred into brain and 38 % into CSF. The transfer of R123 from blood to brain and CSF was lower in postnatal pups and decreased with age (brain: 43 % at P4, 22 % at P14 and 9 % in adults; CSF: 8 % at P4, 8 % at P14 and 1 % in adults). Transfer from maternal blood across placental and brain barriers into fetal brain was approximately 9 %, similar to the transfer across adult blood-brain barriers (also 9 %). Following birth when placental protection was no longer present, transfer of R123 from blood into the newborn brain was significantly higher than into adult brain (3 fold, p < 0.05). Conclusions Administration of a PGP substrate to infant rats resulted in a higher transfer into the brain than equivalent doses at later stages of life or equivalent maternal doses during gestation. Toxicological testing of PGP substrate drugs should consider the possibility of these patient specific differences in safety analysis.

The Blood-Aqueous and Blood-Brain Barriers to Permeability

1988 ◽  
Vol 105 (4) ◽  
pp. 412-416 ◽  
Author(s):  
Gary D. Novack ◽  
Irving H. Leopold
Keyword(s):  
Blood Brain ◽  
Brain Barriers

The Practice of Community Psychiatric Nursing and Mental Health Social Work in Salford Some Implications for Community Care

1988 ◽  
Vol 152 (6) ◽  
pp. 783-792 ◽  
Author(s):  
K. Wooff ◽  
D. P. Goldberg ◽  
T. Fryers
Keyword(s):  
Mental Health ◽  
Psychiatric Symptoms ◽  
Psychiatric Patients ◽  
Psychiatric Nurses ◽  
Health Staff ◽  
Mental Health Staff ◽  
Term Care ◽  
Community Psychiatric ◽  
Wide Range

The context and content of work undertaken with individual clients by community psychiatric nurses (CPNs) and mental health social workers (MHSWs) in Salford were found to be significantly different. Although there were some areas of overlap, the ways in which the two professions worked were quite distinct. MHSWs discussed a wide range of topics and were as concerned with clients' interactions with family and community networks as they were with symptoms. Their interviews with schizophrenic clients followed a similar pattern to those with other groups, and they worked closely with psychiatrists and other mental health staff. CPNs, on the other hand, focused mainly on psychiatric symptoms, treatment arrangements, and medications, and spent significantly less time with individual psychotic clients than they did with patients suffering from neuroses. They were as likely to be in contact with general practitioners as they were with psychiatrists, and had fewer contacts with other mental health staff than the MHSWs. There was evidence that the long-term care of chronic psychiatric patients living outside hospital required more co-ordinated long-term multidisciplinary input.

scholarly journals Correction: High Throughput Measurement of γH2AX DSB Repair Kinetics in a Healthy Human Population

PLoS ONE ◽  
2015 ◽  
Vol 10 (6) ◽  
pp. e0131620 ◽  
Author(s):  
Preety M. Sharma ◽  
Brian Ponnaiya ◽  
Maria Taveras ◽  
Igor Shuryak ◽  
Helen Turner ◽  
...  
Keyword(s):  
High Throughput ◽  
Human Population ◽  
Dsb Repair ◽  
Healthy Human

Ethical Aspects of Using Virtual Reality in Psychiatry

2021 ◽  
Vol 66 (Special Issue) ◽  
pp. 94-94
Author(s):  
Oana Maria Isailă ◽  
◽  
Sorin Hostiuc ◽  
Filip Curcă ◽  
George Cristian Curcă ◽  
...  
Keyword(s):  
Virtual Reality ◽  
Ethical Issues ◽  
Psychiatric Symptoms ◽  
Psychiatric Patients ◽  
Patient Relationship ◽  
Ethical Aspects ◽  
Physician Patient Relationship ◽  
Additional Layer ◽  
Areas Of Interest ◽  
Physician Patient

"Virtual reality (VR), initially a form of entertainment has begun to find its way in healthcare practice. One of its main areas of interest is the treatment of psychiatric disorders. When using VR, the basic ethical principles underlying the physician-patient relationship should be respected, but they should be customized by the presence of an additional layer of complexity generated by the interposition of the virtual world. The physician-patient relationship is often multidirectional, often including a larger team of healthcare professionals, family members or acquaintances, working conjointly to optimize the medical care. Each time other participants are involved within this relationship, the complexity of the ethical issues tends to increase. For example, if the patient has decreased insight, it is possible that other persons must make some medical decisions – resulting a prioritization of beneficence compared to autonomy. Also, we must take into account the fact that many psychiatric symptoms can be seen as a form of “virtual reality” by the patient. The healthcare provider must take additional safety measures to minimize the harms made by VR techniques in psychiatric patients, by using methods that are individually tailored. The main aim of this paper is to debate the ethical aspects surrounding the applicability of virtual reality in treating psychiatric patients, with an emphasis on the elements that were mentioned earlier. "

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