scholarly journals Maternal Immune Activation Sensitizes Male Offspring Rats to Lipopolysaccharide-Induced Microglial Deficits Involving the Dysfunction of CD200–CD200R and CX3CL1–CX3CR1 Systems

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1676
Author(s):  
Katarzyna Chamera ◽  
Magdalena Szuster-Głuszczak ◽  
Ewa Trojan ◽  
Agnieszka Basta-Kaim
Keyword(s):  
Adult Male ◽  
Immune Activation ◽  
Sensorimotor Gating ◽  
Male Offspring ◽  
Sprague Dawley ◽  
Second Hit ◽  
Maternal Immune Activation ◽  
Lps Challenge ◽  
Life Challenges ◽  
Sprague Dawley Rats

Early life challenges resulting from maternal immune activation (MIA) may exert persistent effects on the offspring, including the development of psychiatric disorders, such as schizophrenia. Recent evidence has suggested that the adverse effects of MIA may be mediated by neuron–microglia crosstalk, particularly CX3CL1–CX3CR1 and CD200–CD200R dyads. Therefore, the present study assessed the behavioural parameters resembling schizophrenia-like symptoms in the adult male offspring of Sprague-Dawley rats that were exposed to MIA and to an additional acute lipopolysaccharide (LPS) challenge in adulthood, according to the “two-hit” hypothesis of schizophrenia. Simultaneously, we aimed to clarify the role of the CX3CL1–CX3CR1 and CD200–CD200R axes and microglial reactivity in the brains of adult offspring subjected to MIA and the “second hit” wit LPS. In the present study, MIA generated a range of behavioural changes in the adult male offspring, including increased exploratory activity and anxiety-like behaviours. The most intriguing finding was observed in the prepulse inhibition (PPI) test, where the deficit in the sensorimotor gating was age-dependent and present only in part of the rats. We were able to distinguish the occurrence of two groups: responsive and non-responsive (without the deficit). Concurrently, based on the results of the biochemical studies, MIA disrupted mainly the CD200–CD200R system, while the changes of the CX3CL1–CX3CR1 axis were less evident in the frontal cortex of adult non-responsive offspring. MIA markedly affected the immune regulators of the CD200–CD200R pathway as we observed an increase in cortical IL-6 release in the responsive group and IL-4 in the non-responsive offspring. Importantly, the “second hit” generated disturbances at the behavioural and biochemical levels mostly in the non-responsive adult animals. Those offspring were characterized both by disturbed PPI and “priming” microglia. Altogether, the exposure to MIA altered the immunomodulatory mechanisms, including the CD200–CD200R axis, in the brain and sensitized animals to subsequent immunological challenges, leading to the manifestation of schizophrenia-like alterations.

scholarly journals Maternal Immune Activation during Pregnancy Alters the Behavior Profile of Female Offspring of Sprague Dawley Rats

eNeuro ◽  
2019 ◽  
Vol 6 (2) ◽  
pp. ENEURO.0437-18.2019 ◽  
Author(s):  
Brittney R. Lins ◽  
Wendie N. Marks ◽  
Nadine K. Zabder ◽  
Quentin Greba ◽  
John G. Howland
Keyword(s):  
Immune Activation ◽  
Female Offspring ◽  
Sprague Dawley ◽  
Maternal Immune Activation ◽  
Sprague Dawley Rats ◽  
Behavior Profile

scholarly journals Role of Polyinosinic:Polycytidylic Acid-Induced Maternal Immune Activation and Subsequent Immune Challenge in the Behaviour and Microglial Cell Trajectory in Adult Offspring: A Study of the Neurodevelopmental Model of Schizophrenia

2021 ◽  
Vol 22 (4) ◽  
pp. 1558
Author(s):  
Katarzyna Chamera ◽  
Ewa Trojan ◽  
Katarzyna Kotarska ◽  
Magdalena Szuster-Głuszczak ◽  
Natalia Bryniarska ◽  
...  
Keyword(s):  
Immune Activation ◽  
Mrna Level ◽  
Poly I:C ◽  
Adult Offspring ◽  
Sprague Dawley ◽  
Maternal Immune Activation ◽  
Polyinosinic:Polycytidylic Acid ◽  
Sprague Dawley Rats ◽  
Tnf Α

Multiple lines of evidence support the pathogenic role of maternal immune activation (MIA) in the occurrence of the schizophrenia-like disturbances in offspring. While in the brain the homeostatic role of neuron-microglia protein systems is well documented, the participation of the CX3CL1-CX3CR1 and CD200-CD200R dyads in the adverse impact of MIA often goes under-recognized. Therefore, in the present study, we examined the effect of MIA induced by polyinosinic:polycytidylic acid (Poly I:C) on the CX3CL1-CX3CR1 and CD200-CD200R axes, microglial trajectory (MhcII, Cd40, iNos, Il-1β, Tnf-α, Il-6, Arg1, Igf-1, Tgf-β and Il-4), and schizophrenia-like behaviour in adult male offspring of Sprague-Dawley rats. Additionally, according to the “two-hit” hypothesis of schizophrenia, we evaluated the influence of acute challenge with Poly I:C in adult prenatally MIA-exposed animals on the above parameters. In the present study, MIA evoked by Poly I:C injection in the late period of gestation led to the appearance of schizophrenia-like disturbances in adult offspring. Our results revealed the deficits manifested as a diminished number of aggressive interactions, presence of depressive-like episodes, and increase of exploratory activity, as well as a dichotomy in the sensorimotor gating in the prepulse inhibition (PPI) test expressed as two behavioural phenotypes (MIAPPI-low and MIAPPI-high). Furthermore, in the offspring rats subjected to a prenatal challenge (i.e., MIA) we noticed the lack of modulation of behavioural changes after the additional acute immune stimulus (Poly I:C) in adulthood. The important finding reported in this article is that MIA affects the expression and levels of the neuron-microglia proteins in the frontal cortex and hippocampus of adult offspring. We found that the changes in the CX3CL1-CX3CR1 axis could affect microglial trajectory, including decreased hippocampal mRNA level of MhcII and elevated cortical expression of Igf-1 in the MIAPPI-high animals and/or could cause the up-regulation of an inflammatory response (Il-6, Tnf-α, iNos) after the “second hit” in both examined brain regions and, at least in part, might differentiate behavioural disturbances in adult offspring. Consequently, the future effort to identify the biological background of these interactions in the Poly I:C-induced MIA model in Sprague-Dawley rats is desirable to unequivocally clarify this issue.

Hepatic effects of a highly purified PCB 180 in adult male and female Sprague–Dawley rats

2008 ◽  
Vol 180 ◽  
pp. S39-S40
Author(s):  
Robert Roos ◽  
Patrik Andersson ◽  
Päivi Heikkinen ◽  
Hans-Joachim Schmitz ◽  
Leo van der Ven ◽  
...  
Keyword(s):  
Adult Male ◽  
Sprague Dawley ◽  
Male And Female ◽  
Sprague Dawley Rats

scholarly journals Prospective Analysis of the Effects of Maternal Immune Activation on Rat Cytokines during Pregnancy and Behavior of the Male Offspring Relevant to Schizophrenia

eNeuro ◽  
2018 ◽  
Vol 5 (4) ◽  
pp. ENEURO.0249-18.2018 ◽  
Author(s):  
Brittney R. Lins ◽  
Jessica L. Hurtubise ◽  
Andrew J. Roebuck ◽  
Wendie N. Marks ◽  
Nadine K. Zabder ◽  
...  
Keyword(s):  
Immune Activation ◽  
Male Offspring ◽  
Prospective Analysis ◽  
Maternal Immune Activation ◽  
And Behavior

scholarly journals Effects of Aqueous Quassia amara L. (Korales) Leaf Extract on the Cardiovascular and Respiratory Functions of Male Sprague-Dawley Rats

2018 ◽  
Vol 52 (6) ◽  
Author(s):  
Maria Concepcion C. Sison ◽  
Lynn Crisanta R. Panganiban ◽  
Daisy Mae A. Bagaoisan ◽  
Nelia P. Cortes-Maramba
Keyword(s):  
Blood Pressure ◽  
Adult Male ◽  
Leaf Extract ◽  
Sprague Dawley ◽  
Treatment Groups ◽  
Respiratory Flow ◽  
Sprague Dawley Rats ◽  
Parallel Group ◽  
Aqueous Leaf Extract ◽  
Quassia Amara

Objective. To To evaluate potential effects of the aqueous extract of Quassia amara L. leaves on the cardiovascular and respiratory systems of adult male Sprague- Dawley rats. Methods. The cardiovascular and respiratory effects of the Quassia amara L. leaf extract on adult male SpragueDawley rats were assessed using non-invasive blood pressure (NIBP) determination and head-out plethysmography, respectively, in a randomized, parallel group study. Mean observations of blood pressure and heart rate were recorded at different time periods after dosing. Respiratory flow and irritation effects were evaluated using mean observations of respiratory rate (RR), tidal volume (TV), mid-expiratory flow rate (EF50), time of inspiration (TI) and expiration (TE), and time of break (TB) and pause (TP). Results. There were no significant differences among the control and the treatment groups in SBP, DBP and HR parameters. The extract showed statistically significant effect on mean RR by time period (F=2.45, p=0.0234), trends over time of TV among the dose groups (F=2.00, p=0.0202), and EF50 among dose groups ((F=3.11, p=0.0422). However, these did not correlate with the changes in the time of break (TB) and time of pause (TP) which are more sensitive and specific tests for respiratory irritation. Conclusion. Aqueous leaf extract of Quassia appeared to have no significant effects on SBP, DPB, Pulse pressure, and HR. There are no conclusive dose-related respiratory flow or pulmonary irritation effects.

scholarly journals Synergistic toxicity in an in vivo model of neurodegeneration through the co-expression of human TDP-43M337V and tauT175D protein

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Alexander J. Moszczynski ◽  
Madeline Harvey ◽  
Niveen Fulcher ◽  
Cleusa de Oliveira ◽  
Patrick McCunn ◽  
...  
Keyword(s):  
Tau Protein ◽  
Sensorimotor Gating ◽  
In Vivo Model ◽  
Motor Deficits ◽  
Sprague Dawley ◽  
Tau Pathology ◽  
Adult Rats ◽  
Sprague Dawley Rats ◽  
Somatic Gene Transfer

Abstract Although it has been suggested that the co-expression of multiple pathological proteins associated with neurodegeneration may act synergistically to induce more widespread neuropathology, experimental evidence of this is sparse. We have previously shown that the expression of Thr175Asp-tau (tauT175D) using somatic gene transfer with a stereotaxically-injected recombinant adeno-associated virus (rAAV9) vector induces tau pathology in rat hippocampus. In this study, we have examined whether the co-expression of human tauT175D with mutant human TDP-43 (TDP-43M337V) will act synergistically. Transgenic female Sprague-Dawley rats that inducibly express mutant human TDP-43M337V using the choline acetyltransferase (ChAT) tetracycline response element (TRE) driver with activity modulating tetracycline-controlled transactivator (tTA) were utilized in these studies. Adult rats were injected with GFP-tagged tau protein constructs in a rAAV9 vector through bilateral stereotaxic injection into the hippocampus. Injected tau constructs were: wild-type GFP-tagged 2N4R human tau (tauWT; n = 8), GFP-tagged tauT175D 2N4R human tau (tauT175D, pseudophosphorylated, toxic variant, n = 8), and GFP (control, n = 8). Six months post-injection, mutant TDP-43M337V expression was induced for 30 days. Behaviour testing identified motor deficits within 3 weeks after TDP-43 expression irrespective of tau expression, though social behaviour and sensorimotor gating remained unchanged. Increased tau pathology was observed in the hippocampus of both tauWT and tauT175D expressing rats and tauT175D pathology was increased in the presence of cholinergic neuronal expression of human TDP-43M337V. These data indicate that co-expression of pathological TDP-43 and tau protein exacerbate the pathology associated with either individual protein.

Sign in / Sign up

Export Citation Format

Share Document