scholarly journals Subtle alterations in neonatal neurodevelopment following early or late exposure to prenatal maternal immune activation

2021 ◽  
Author(s):  
Elisa Guma ◽  
Emily Snook ◽  
Shoshana Spring ◽  
Jason P Lerch ◽  
Brian J Nieman ◽  
...  
Keyword(s):  
Immune Activation ◽  
Neonatal Period ◽  
Ex Vivo ◽  
Brain Anatomy ◽  
Cross Sectional ◽  
Maternal Immune Activation ◽  
Communicative Ability ◽  
Late Exposure ◽  
Magnetic Resonance Imaging Mri ◽  
The Impact

Prenatal exposure to maternal immune activation (MIA) is a risk factor for a variety of neurodevelopmental and psychiatric disorders. The timing of MIA-exposure has been shown to affect adolescent and adult offspring neurodevelopment, however, less is known about these effects in the neonatal period. To better understand the impact of MIA-exposure on neonatal brain development, we first assess neonate communicative abilities with the ultrasonic vocalization task, followed by high-resolution ex vivo magnetic resonance imaging (MRI) on the neonatal (postnatal day 8) brain. Early exposed offspring displayed decreased communicative ability, while brain anatomy appeared largely unaffected, apart from some subtle alterations. By integrating MRI and behavioural assays to investigate the effects of MIA-exposure on neonatal neurodevelopment we show that offspring neuroanatomy and behaviour are only subtly affected by both early and late exposure. This suggests that the deficits often observed in later stages of life may be dormant, not yet developed in the neonatal period, or not as easily detectable using a cross-sectional approach.

scholarly journals Differential effects of early or late exposure to prenatal maternal immune activation on mouse embryonic neurodevelopment

2021 ◽  
Author(s):  
Elisa Guma ◽  
Maude Bordeleau ◽  
Emily Snook ◽  
Gabriel Desrosiers-Gregoire ◽  
Fernando Gonzalez Ibanez ◽  
...  
Keyword(s):  
Immune Activation ◽  
Ex Vivo ◽  
Apoptotic Cell ◽  
Imaging Techniques ◽  
Differential Effects ◽  
Maternal Immune Activation ◽  
Late Exposure ◽  
Magnetic Resonance Imaging Mri ◽  
And Oxidative Stress ◽  
Embryo Brain

Exposure to maternal immune activation (MIA) in utero is a risk factor for neurodevelopmental and psychiatric disorders. MIA-induced deficits in adolescent and adult offspring have been well characterized, however, less is known about the effects of MIA-exposure on embryo development. To address this gap, we performed high-resolution ex vivo magnetic resonance imaging (MRI) to investigate the effects of early (gestational day [GD]9) and late (GD17) MIA-exposure on embryo (GD18) brain structure. We identify striking neuroanatomical changes in the embryo brain, particularly in the late exposed offspring. We further examined hippocampal neuroanatomy using electron microscopy and identified differential effects due to MIA-timing. An increase in apoptotic cell density was observed in the GD9 exposed offspring, while an increase in the density of dark neurons and glia, putative markers for increased neuroinflammation and oxidative stress, was observed in GD17 exposed offspring, particularly in females. Overall, our findings integrate imaging techniques across different scales to identify differential impact of MIA-timing on the earliest stages of neurodevelopment.

scholarly journals Preliminary evidence that maternal immune activation specifically increases diagonal domain volume in the rat brain during early postnatal development

2018 ◽  
Author(s):  
Tobias C. Wood ◽  
Michelle E. Edye ◽  
Michael K. Harte ◽  
Joanna C. Neill ◽  
Eric P. Prinssen ◽  
...  
Keyword(s):  
Rat Brain ◽  
Immune Activation ◽  
Diffusion Tensor ◽  
Ex Vivo ◽  
Morphological Changes ◽  
Female Offspring ◽  
Preliminary Evidence ◽  
Poly I:C ◽  
Maternal Immune Activation ◽  
The Impact

AbstractMaternal immune activation (MIA) is consistently associated with elevated risk for multiple psychiatric disorders in the affected offspring. Related to this, an important goal of our work is to explore the impact of MIA effects across the lifespan. In this context, we recently reported the effects of poly (I:C)-induced MIA at gestational day (GD)15, immediately prior to birth, at GD21 and again at post-natal day (PD)21, providing a systematic assessment of plasma IL-6, body temperature and weight alterations in pregnant rats following poly (I:C) exposure and preliminary evidence for gross morphological changes and microglial neuropathology in both male and female offspring at GD21 and PD21. Here, we sought to complement and extend these data by characterising in more detail the meso-scale impact of gestational poly (I:C) exposure at GD15 on the neuroanatomy of the juvenile (PD21) rat brain using high-resolution, ex vivo anatomical magnetic resonance imaging (MRI) in combination with atlas-based segmentation. Our preliminary data suggest subtle neuroanatomical effects of gestational poly (I:C) exposure (n=10) relative to saline controls (n=10) at this time-point. Specifically, we report here preliminary evidence for a significant increase in the relative volume of the diagonal domain in poly (I:C) offspring (p<0.01; q<0.1), particularly in female offspring. This occurred in the absence of any microstructural alterations as detectable using diffusion tensor imaging (DTI). Longitudinal in vivo studies, informed by the effect sizes from this dataset are now required to establish both the functional relevance and cellular mechanisms of the apparent DD volume increase.

scholarly journals Mapping the impact of exposure to maternal immune activation on juvenile Wistar rat brain macro- and microstructure during early post-natal development

2019 ◽  
Vol 3 ◽  
pp. 239821281988308
Author(s):  
Tobias C. Wood ◽  
Michelle E. Edye ◽  
Michael K. Harte ◽  
Joanna C. Neill ◽  
Eric P. Prinssen ◽  
...  
Keyword(s):  
Rat Brain ◽  
Immune Activation ◽  
Diffusion Tensor ◽  
Ex Vivo ◽  
Morphological Changes ◽  
Relative Volume ◽  
Acid Exposure ◽  
Pregnant Rats ◽  
Maternal Immune Activation ◽  
The Impact

Maternal immune activation is consistently associated with elevated risk for multiple psychiatric disorders in the affected offspring. Related to this, an important goal of our work is to explore the impact of maternal immune activation effects across the lifespan. In this context, we recently reported the effects of polyriboinosinic-polyribocytidylic acid–induced maternal immune activation at gestational day 15, immediately prior to birth, at gestational day 21 and again at post-natal day 21, providing a systematic assessment of plasma interleukin 6, body temperature and weight alterations in pregnant rats and preliminary evidence for gross morphological changes and microglial neuropathology in both male and female offsprings at these time points. Here, we sought to complement and extend these data by characterising in more detail the mesoscale impact of gestational polyriboinosinic-polyribocytidylic acid exposure at gestational day 15 on the neuroanatomy of the juvenile (post-natal day 21) rat brain using high-resolution, ex vivo anatomical magnetic resonance imaging in combination with atlas-based segmentation. Our preliminary data suggest subtle neuroanatomical effects of gestational polyriboinosinic-polyribocytidylic acid exposure (n = 10) relative to saline controls (n = 10) at this time-point. Specifically, we found an increase in the relative volume of the diagonal domain in polyriboinosinic-polyribocytidylic acid offspring (p < 0.01 uncorrected), which just failed to pass stringent multiple comparisons correction (actual q = 0.07). No statistically significant microstructural alterations were detectable using diffusion tensor imaging. Further studies are required to map the proximal effects of maternal immune activation on the developing rodent brain from foetal to early post-natal life and confirm our findings herein.

scholarly journals The Effect of Maternal Immune Activation on Social Play-Induced Ultrasonic Vocalization in Rats

2021 ◽  
Vol 11 (3) ◽  
pp. 344
Author(s):  
Kinga Gzielo ◽  
Agnieszka Potasiewicz ◽  
Ewa Litwa ◽  
Diana Piotrowska ◽  
Piotr Popik ◽  
...  
Keyword(s):  
Immune Activation ◽  
Social Play ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Male Rats ◽  
Poly I:C ◽  
Maternal Immune Activation ◽  
Increased Risk ◽  
Adolescent Rats ◽  
The Impact

Prenatal maternal infection is associated with an increased risk of various neurodevelopmental disorders, including autism spectrum disorders (ASD). Maternal immune activation (MIA) can be experimentally induced by prenatal administration of polyinosinic:polycytidylic acid (poly I:C), a synthetic viral-like double-stranded RNA. Although this MIA model is adopted in many studies, social and communicative deficits, included in the first diagnostic criterion of ASD, are poorly described in the offspring of poly(I:C)-exposed dams. This study aimed to characterize the impact of prenatal poly(I:C) exposure on socio-communicative behaviors in adolescent rats. For this purpose, social play behavior was assessed in both males and females. We also analyzed quantitative and structural changes in ultrasonic vocalizations (USVs) emitted by rats during the play test. Deficits of social play behaviors were evident only in male rats. Males also emitted a significantly decreased number of USVs during social encounters. Prenatal poly(I:C) exposure also affected acoustic call parameters, as reflected by the increased peak frequencies. Additionally, repetitive behaviors were demonstrated in autistic-like animals regardless of sex. This study demonstrates that prenatal poly(I:C) exposure impairs socio-communicative functioning in adolescent rats. USVs may be a useful tool for identifying early autistic-like abnormalities.

scholarly journals Neurodevelopmental Disorders Induced by Maternal Immune Activation: Toward a Prevention Strategy in the Era of the COVID-19 Pandemic

2020 ◽  
Vol 1 (1) ◽  
pp. 24-26
Author(s):  
Kazuhiro Sakurada ◽  
Yoshihiro Noda
Keyword(s):  
Immune Activation ◽  
Neurodevelopmental Disorders ◽  
Data Science ◽  
Biological Effects ◽  
Global Scale ◽  
Maternal Infection ◽  
Public Health Perspective ◽  
Daily Lives ◽  
Maternal Immune Activation ◽  
The Impact

As of summer 2020, the COVID-19 pandemic is having a major impact on our daily lives on a global scale, forcing us to change to the new normal. However, the effects are not only detrimental to our present socioeconomic conditions but also have the risk of having negative biological effects on our descendants. Of concern is the effect of maternal immune activation following maternal infection with COVID-19 on the fetus’ cerebral nervous system. While we are currently occupied with countering the imminent threats in front of us, we also need to take steps from a public health perspective to reduce the impact of maternal infection on the fetus, especially the risk of neurodevelopmental disorders. However, such a risk can be prevented and managed through the digital transformation of the nation’s health data and the strategic application of sophisticated data science approaches to those big data.

scholarly journals Moderate to intense physical activity is associated with improved clinical, CD4/CD8 ratio and immune activation status in HIV infected patients on ART

2021 ◽  
Author(s):  
Enrique Bernal ◽  
Monica Martinez ◽  
José Antonio Campillo ◽  
Gabriel Puche ◽  
Carlos Baguena ◽  
...  
Keyword(s):  
Physical Activity ◽  
T Lymphocytes ◽  
Immune Activation ◽  
Healthy Lifestyle ◽  
Moderate Physical Activity ◽  
Cross Sectional ◽  
Hla Dr ◽  
The Impact ◽  
Intense Physical Activity ◽  
Activation Status

Abstract Background Physical activity has anti-inflammatory effects and reduces morbidity and mortality in general population, but its role in the clinical, CD4/CD8 ratio and immune activation status in HIV-infected patients has been poorly studied. Methods A cross-sectional study was carried out in a cohort of 155 HIV-infected patients on stable ART to compare clinical, biochemical, CD4/CD8 ratio and immune-activation status according to their physical activity in the last two years (sedentary/low vs. moderate/intense) assessed by the iPAQ. A binary logistic regression and mixed ANOVA were performed to evaluate the impact of levels of physical activity on CD4/CD8 ratio. Results In our series 77 (49.7%) out of 155 patients were sedentary and 78 (50.3%) practiced moderate/intense physical activity. Moderate/intense physical activity was associated with lower CDC HIV-stage (p=0.046), better metabolic control (lower BMI, p=0.024; glucose, p=0.024; and triglyceride, p=0.002), higher CD3 +CD4 + T lymphocytes (p=0.016), lower CD8 + T lymphocytes (p=0.018), higher CD4/CD8 ratio (p=0.001), lower CD4 +CD8 + (p=0.026), CD4 +CD86 + (p=0.045), CD4 +HLA-DR + (p=0.011), CD8 +HLA-DR + (p=0.048) T lymphocytes and CD16 +HLA-DR + NK cells (p=0.026). Sedentary lifestyle (OR=2.12, p=0.042), CD4 nadir (OR=1.005, p&lt;0.001) and CD8 +CD38 + T cells (OR=1.27, p=0.006) were independently associated with low CD4/CD8 ratio (&lt;0.8). Earlier and more intense CD4/CD8 ratio recovery was observed in patients with higher physical activity in the two-year follow-up with a significant interaction between these variables: F(2, 124) = 3.31, p=0.049, partial η2=0.042). Conclusions Moderate to high physical activity is associated with beneficial health effects, improving metabolic profile and reducing chronic inflammation in patients living with HIV. Although more studies and clinical trials are needed to confirm these findings, healthy lifestyle, including at least moderate physical activity, should be recommended to HIV patients on stable ART.

scholarly journals A Salivation Abnormality with Trigeminal Nerve Dysfunction in Dogs

2019 ◽  
Vol 36 (1) ◽  
pp. 8-16 ◽  
Author(s):  
Marc Kent ◽  
Rachel B. Song ◽  
Eric N. Glass ◽  
Alexander de Lahunta
Keyword(s):  
Oral Health ◽  
Salivary Glands ◽  
Trigeminal Nerve ◽  
Motor Dysfunction ◽  
Area Measurement ◽  
Parasympathetic Innervation ◽  
Cross Sectional ◽  
Magnetic Resonance Imaging Mri ◽  
Mri Changes ◽  
The Impact

Trigeminal nerve pathology can lead to sensory and motor dysfunction to structures of the head that are easily recognized. The trigeminal nerve is a conduit for the distribution of postganglionic parasympathetic innervation to structures of the head. Parasympathetic innervation to the salivary glands is provided by preganglionic parasympathetic neurons of the facial and glossopharyngeal nerves. Postganglionic axons course with branches of the mandibular branch of the trigeminal nerve to reach the salivary glands. Denervation of the salivary glands impacts glandular function, leading to a reduction in the volume and composition of the saliva produced. Saliva plays an important role in oral health. Poor oral health has widespread systemic implications. This article describes a group of dogs with unilateral or bilateral dysfunction of the trigeminal nerve and/or its branches. In all dogs, an accumulation of thick, foamy saliva was observed accumulating in the dorsal aspect of the caudal oral cavity on the ipsilateral side to the affected nerve. In dogs with magnetic resonance imaging (MRI), there was a reduction in size based on the largest cross-sectional area measurement and an increase in mean signal intensity of the salivary glands ipsilateral to the affected nerves compared to the glands on the normal side. The authors hypothesize that the abnormal saliva and MRI changes observed were consequent to parasympathetic denervation of the salivary glands. The recognition of this clinical observation is the first step in understanding the impact that denervation has on salivation and ultimately on overall oral and systemic health in dogs.

scholarly journals Investigating the Effect of Reduced Serotonin Transporter Expression in a Maternal Immune Activation Model of Neurodevelopmental Disorders

2021 ◽  
Author(s):  
◽  
Alexandra Lister
Keyword(s):  
Serotonin Transporter ◽  
Immune Activation ◽  
Neurodevelopmental Disorders ◽  
Allelic Variation ◽  
Autism Spectrum ◽  
Poly I:C ◽  
Supporting Evidence ◽  
Maternal Immune Activation ◽  
Behavioural Effects ◽  
The Impact

<p>Maternal Immune Activation (MIA) during early pregnancy is an established risk factor for the occurrence of neurodevelopmental disorders such as Autism Spectrum Disorder (ASD) and schizophrenia (SCZ) in offspring. Serotonin signalling is also implicated in both ASD and SCZ, in conjunction with a known and extensive influence in neural development. Using a Wistar serotonin transporter (SERT) knockout model to mimic allelic variation in the human serotonin transporter promoter (5‐HTTLPR), this research investigates the impact of full or reduced SERT function on the effect of poly I:C-induced MIA in offspring. Experimental design focuses on ultrasonic vocalisation communication in postnatal day (PND) 7 offspring, followed by genetic expression of the Rac1/Kal7/Disc1 signalosome pathway at PND21 previously implicated in SCZ pathology. Results from behavioural analysis of pups indicate a statistically significant increase in calling and call complexity in pups heterozygous for the SERT (SERT HET) compared to wildtype (WT). When separated by sex, this trend remains consistent however only reaches significance in male offspring. Male SERT HET pups also a significant treatment effect in call complexity, and a significant genotype/treatment interaction which suggests an increased susceptibility to MIA-induced behavioural effects. Additionally, poly I:C exposed pups show increased expression of Disc1, supporting evidence that this pathway may be affected in neurodevelopmental disorders. No genotype and sex effects were observed in signalosome expression; however, this study may be too underpowered to detect these effects. These results suggest that differences between sex and SERT genotype in offspring may modulate the behavioural effects of MIA in rodent models of NDD, with more study required to assess these differences in a molecular context. Furthermore, this study aims to address the overall inconsistency and misrepresentation of statistical methods in MIA models by employing MIA validation tests and linear mixed modelling to account for litter variation. In summary, the research presented in this thesis reports initial evidence suggesting SERT genotype may influence the effect of MIA, however further research is necessary to characterise the effect of genotype on MIA challenge during gestation.</p>

scholarly journals Investigating the Effect of Reduced Serotonin Transporter Expression in a Maternal Immune Activation Model of Neurodevelopmental Disorders

2021 ◽  
Author(s):  
◽  
Alexandra Lister
Keyword(s):  
Serotonin Transporter ◽  
Immune Activation ◽  
Neurodevelopmental Disorders ◽  
Allelic Variation ◽  
Autism Spectrum ◽  
Poly I:C ◽  
Supporting Evidence ◽  
Maternal Immune Activation ◽  
Behavioural Effects ◽  
The Impact

<p>Maternal Immune Activation (MIA) during early pregnancy is an established risk factor for the occurrence of neurodevelopmental disorders such as Autism Spectrum Disorder (ASD) and schizophrenia (SCZ) in offspring. Serotonin signalling is also implicated in both ASD and SCZ, in conjunction with a known and extensive influence in neural development. Using a Wistar serotonin transporter (SERT) knockout model to mimic allelic variation in the human serotonin transporter promoter (5‐HTTLPR), this research investigates the impact of full or reduced SERT function on the effect of poly I:C-induced MIA in offspring. Experimental design focuses on ultrasonic vocalisation communication in postnatal day (PND) 7 offspring, followed by genetic expression of the Rac1/Kal7/Disc1 signalosome pathway at PND21 previously implicated in SCZ pathology. Results from behavioural analysis of pups indicate a statistically significant increase in calling and call complexity in pups heterozygous for the SERT (SERT HET) compared to wildtype (WT). When separated by sex, this trend remains consistent however only reaches significance in male offspring. Male SERT HET pups also a significant treatment effect in call complexity, and a significant genotype/treatment interaction which suggests an increased susceptibility to MIA-induced behavioural effects. Additionally, poly I:C exposed pups show increased expression of Disc1, supporting evidence that this pathway may be affected in neurodevelopmental disorders. No genotype and sex effects were observed in signalosome expression; however, this study may be too underpowered to detect these effects. These results suggest that differences between sex and SERT genotype in offspring may modulate the behavioural effects of MIA in rodent models of NDD, with more study required to assess these differences in a molecular context. Furthermore, this study aims to address the overall inconsistency and misrepresentation of statistical methods in MIA models by employing MIA validation tests and linear mixed modelling to account for litter variation. In summary, the research presented in this thesis reports initial evidence suggesting SERT genotype may influence the effect of MIA, however further research is necessary to characterise the effect of genotype on MIA challenge during gestation.</p>

scholarly journals Subtle alterations in neonatal neurodevelopment following early or late exposure to prenatal maternal immune activation in mice

2021 ◽  
pp. 102868
Author(s):  
Elisa Guma ◽  
Emily Snook ◽  
Shoshana Spring ◽  
Jason P. Lerch ◽  
Brian J. Nieman ◽  
...  
Keyword(s):  
Immune Activation ◽  
Maternal Immune Activation ◽  
Late Exposure
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