The effect of 17β-estradiol on maternal immune activation-induced changes in prepulse inhibition and dopamine receptor and transporter binding in female rats

2020 ◽  
Vol 223 ◽  
pp. 249-257 ◽  
Author(s):  
Alyssa Sbisa ◽  
Snezana Kusljic ◽  
Damon Zethoven ◽  
Maarten van den Buuse ◽  
Andrea Gogos
Keyword(s):  
Dopamine Receptor ◽  
Prepulse Inhibition ◽  
Immune Activation ◽  
Female Rats ◽  
Maternal Immune Activation ◽  
17Β Estradiol ◽  
Induced Changes

scholarly journals Estrogen Modulates Endothelial and Neuronal Nitric Oxide Synthase Expression via an Estrogen Receptor β-Dependent Mechanism in Hypothalamic Slice Cultures

Endocrinology ◽  
2005 ◽  
Vol 146 (7) ◽  
pp. 2933-2941 ◽  
Author(s):  
Sarah Gingerich ◽  
Teresa L. Krukoff
Keyword(s):  
Nitric Oxide ◽  
Estrogen Receptor ◽  
Female Rats ◽  
Inhibitory Effects ◽  
17Β Estradiol ◽  
Hypothalamic Slice ◽  
Blood Pressure Responses ◽  
Induced Changes ◽  
Oxide Synthase ◽  
Brain Nitric Oxide

Abstract Although it is evident that estrogen has important physiological effects in the brain, the signaling mechanisms mediating these effects remain unclear. We recently showed that estrogen mediates attenuated blood pressure responses to psychological stress in ovariectomized female rats through brain nitric oxide (NO). An area likely to mediate these effects is the hypothalamic paraventricular nucleus (PVN), because here NO exerts inhibitory effects on autonomic output to the periphery. Because little is known about how estrogen acts on the NO system in the PVN, our aim was to study the effects of estrogen on the NO system in the PVN of hypothalamic slices cultures. We show that 17β-estradiol (E2; 1 nm) increases endothelial NO synthase (eNOS) protein expression and decreases the numbers of neuronal NOS (nNOS)-positive neurons in the PVN after 8 and 24 h, respectively. Using the nonselective estrogen receptor (ER) antagonist, ICI 182,780 (10 nm), we determined that E2-induced changes in NOS expression in the PVN are ER dependent. Using the ERβ agonist, genistein (0.1 μm), we determined that activation of ERβ induces increased eNOS expression and a decreased number of nNOS-positive neurons. We used the selective ERα agonist, propyl-pyrazole-triol (10 nm), and antagonist, methyl-piperidino-pyrazole (1 μm), to exclude the possibility that ERα is involved in the E2-induced increase in eNOS and nNOS in the PVN. These results demonstrate that E2 induces changes in NOS expression in the PVN and that these effects are ERβ dependent.

scholarly journals The Synaptic Dysregulation in Adolescent Rats Exposed to Maternal Immune Activation

2021 ◽  
Vol 13 ◽  
Author(s):  
Magdalena Cieślik ◽  
Magdalena Gassowska-Dobrowolska ◽  
Aleksandra Zawadzka ◽  
Małgorzata Frontczak-Baniewicz ◽  
Magdalena Gewartowska ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Immune Activation ◽  
Mitochondrial Membrane ◽  
Molecular Mechanisms ◽  
Glycogen Synthase ◽  
Synaptic Proteins ◽  
Female Rats ◽  
Maternal Immune Activation ◽  
Adolescent Rats

Maternal immune activation (MIA) is a risk factor for neurodevelopmental disorders in offspring, but the pathomechanism is largely unknown. The aim of our study was to analyse the molecular mechanisms contributing to synaptic alterations in hippocampi of adolescent rats exposed prenatally to MIA. MIA was evoked in pregnant female rats by i.p. administration of lipopolysaccharide at gestation day 9.5. Hippocampi of offspring (52–53-days-old rats) were analysed using transmission electron microscopy (TEM), qPCR and Western blotting. Moreover, mitochondrial membrane potential, activity of respiratory complexes, and changes in glutathione system were measured. It was found that MIA induced changes in hippocampi morphology, especially in the ultrastructure of synapses, including synaptic mitochondria, which were accompanied by impairment of mitochondrial electron transport chain and decreased mitochondrial membrane potential. These phenomena were in agreement with increased generation of reactive oxygen species, which was evidenced by a decreased reduced/oxidised glutathione ratio and an increased level of dichlorofluorescein (DCF) oxidation. Activation of cyclin-dependent kinase 5, and phosphorylation of glycogen synthase kinase 3β on Ser9 occurred, leading to its inhibition and, accordingly, to hypophosphorylation of microtubule associated protein tau (MAPT). Abnormal phosphorylation and dysfunction of MAPT, the manager of the neuronal cytoskeleton, harmonised with changes in synaptic proteins. In conclusion, this is the first study demonstrating widespread synaptic changes in hippocampi of adolescent offspring prenatally exposed to MIA.

TrkB agonist 7,8-dihydroxyflavone reverses an induced prepulse inhibition deficit selectively in maternal immune activation offspring

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Emily J. Jaehne ◽  
Elaine Mei San Chong ◽  
Alyssa Sbisa ◽  
Brendan Gillespie ◽  
Rachel Hill ◽  
...  
Keyword(s):  
Prepulse Inhibition ◽  
Immune Activation ◽  
Maternal Immune Activation

scholarly journals Paliperidone Reversion of Maternal Immune Activation-Induced Changes on Brain Serotonin and Kynurenine Pathways

2021 ◽  
Vol 12 ◽  
Author(s):  
Karina S. MacDowell ◽  
Eva Munarriz-Cuezva ◽  
J. Javier Meana ◽  
Juan C. Leza ◽  
Jorge E. Ortega
Keyword(s):  
Immune Activation ◽  
Kynurenic Acid ◽  
Tryptophan Hydroxylase ◽  
Poly I:C ◽  
Neuroprotective Activity ◽  
Alternative Activation ◽  
Antipsychotic Treatment ◽  
Maternal Immune Activation ◽  
Induced Changes

Emerging evidence indicates that early-life exposure to environmental factors may increase the risk for schizophrenia via inflammatory mechanisms. Inflammation can alter the metabolism of tryptophan through the oxidative kynurenine pathway to compounds with neurotoxic and neuroprotective activity and compromise serotonin (5-HT) synthesis. Here we investigate the role of serotonergic and kynurenine pathways in the maternal immune activation (MIA) animal model of schizophrenia. The potential reversion exerted by long-term antipsychotic treatment was also evaluated. MIA was induced by prenatal administration of polyinosinic:polycytidylic acid (poly (I:C)) in mice. Expression of different proteins and the content of different metabolites involved in the function of serotonergic and kynurenine pathways was assessed by RT-PCR, immunoblot and ELISA analyses in frontal cortex of the offspring after puberty. MIA decreased tissue 5-HT content and promoted changes in the expression of serotonin transporter, 5-HT2A and 5-HT2C receptors. Expression of indoleamine 2,3-dioxygenase 2 (IDO2) and kynurenine 3-monooxygenase (KMO) was increased by poly (I:C) whereas kynurenine aminotransferase II and its metabolite kynurenic acid were not altered. Long-term paliperidone was able to counteract MIA-induced changes in 5-HT and KMO, and to increase tryptophan availability and tryptophan hydroxylase-2 expression in poly (I:C) mice but not in controls. MIA-induced increase of the cytotoxic risk ratio of kynurenine metabolites (quinolinic/kynurenic acid) was also reversed by paliperidone. MIA induces specific long-term brain effects on serotonergic activity. Such effects seem to be related with alternative activation of the kynurenine metabolic pathway towards a cytotoxic status. Atypical antipsychotic paliperodine partially remediates abnormalities observed after MIA.

scholarly journals Inter‐breeder differences in prepulse inhibition deficits of C57BL/6J mice in a maternal immune activation model

2021 ◽  
Author(s):  
Yutaro Kobayashi ◽  
Hiroyoshi Inaba ◽  
Yuriko Iwakura ◽  
Hisaaki Namba ◽  
Hidekazu Sotoyama ◽  
...  
Keyword(s):  
Prepulse Inhibition ◽  
Immune Activation ◽  
Activation Model ◽  
Maternal Immune Activation

scholarly journals Got Milk? Maternal immune activation during the mid-lactational period affects nutritional milk quality and adolescent offspring sensory processing in male and female rats

2022 ◽  
Author(s):  
Holly DeRosa ◽  
Hieu Tran ◽  
Amanda C Kentner
Keyword(s):  
Animal Models ◽  
Immune Activation ◽  
Maternal Care ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Female Rats ◽  
Maternal Immune Activation ◽  
Adolescent Offspring ◽  
And Behavior

The neonatal environment requires a high level of maternal demand in terms of both breastfeeding and other forms of maternal care. Previous studies have underscored the importance of these maternal factors on offspring development and behavior. However, their contribution as dynamic variables in animal models of early life stress are often overlooked. In the present study, we show that lipopolysaccharide (LPS)-induced maternal immune activation (MIA) on postnatal day (P)10 immediately elevated milk corticosterone concentrations, which recovered by P11. In contrast, both milk triglyceride and percent creamatocrit values demonstrated a prolonged decrease following inflammatory challenge. Sustained inflammatory-induced changes to the nutritional quality of milk were also evidenced by its composition of microbial communities associated with inefficient energy and lipid metabolism. Nutritional deficits in early development have been associated with metabolic dysfunction later in life. Indeed, MIA-associated changes in the nutritional profile of milk were reflected by increased adolescent offspring bodyweights. While MIA did not decrease maternal care quality, there was a significant compensatory increase in maternal licking and grooming the day that followed the inflammatory challenge. However, this did not protect against disrupted neonatal huddling or later-life alterations in sensorimotor gating and mechanical allodynia in MIA offspring. Animal models of early life stress can impact both parents and their offspring. One mechanism that can mediate the effects of such stressors is changes to maternal lactation quality which our data show can confer multifaceted and compounding effects on offspring physiology and behavior.

scholarly journals A Proof-of-Concept Study of Maternal Immune Activation Mediated Induction of Toll-Like Receptor (TLR) and Inflammasome Pathways Leading To Neuroprogressive Changes and Schizophrenia-Like Behaviors in Offspring.

2021 ◽  
Author(s):  
Pinku Mani Talukdar ◽  
Fazal Abdul ◽  
Michael Maes ◽  
Michael Berk ◽  
Ganesan Venkatasubramanian ◽  
...  
Keyword(s):  
Prepulse Inhibition ◽  
Immune Activation ◽  
Inflammatory Responses ◽  
Poly I:C ◽  
Sprague Dawley ◽  
Maternal Immune Activation ◽  
Prenatal Infection ◽  
Prenatal Infections ◽  
Apoptotic Pathways ◽  
Few Data

Abstract Infection, particularly prenatal infection leads to an enhanced risk of schizophrenia in the offspring. Interestingly, few data exist on the pathway(s) such as TLR and inflammasome, primarily involved in sensing the microorganisms and inducing downstream inflammatory responses, apoptosis and neuroprogressive changes in the prenatal infection-induced risk of schizophrenia. Herein, we aimed to discern whether prenatal infection-induced maternal immune activation (MIA) causes schizophrenia-like behaviors through activation of TLR and inflammasome pathways in the brain of offspring. Sprague Dawley rats (n=15/group) were injected either with poly (I:C) or LPS or saline at gestational day (GD)-12. Significantly elevated plasma levels of IL-1β, IL-6, TNF-α and IL-17A assessed after 24 hours were observed in poly (I:C) and LPS-treated rats, indicating MIA. The offspring rats of poly (I:C)-and LPS-treated dams displayed increased anxiety-like behaviors, deficits in social behaviors and prepulse inhibition. The hippocampus of offspring rats showed increased expression of TLR3, TLR4, NLRP3, IL-1β, and IL-18 of poly (I:C) and TLR3, TLR4, NLRP3, Cas1, IL-1β, and IL-18 of LPS-treated dams. Notably, the expression of these genes showed a positive correlation with apoptotic and a negative correlation with neuroprotective genes. Furthermore, TLR and inflammasome genes had significant impact on social deficits and impaired prepulse inhibition in offspring rats. The results suggest MIA due to prenatal infection perhaps trigger TLR, inflammasome and apoptotic pathways leading to the induction of schizophrenia-like behaviors in the later stages of life. Prenatal infections seem to drive neuroprogression and subsequently schizophrenia-like symptoms through a common central pathway involving TLR, inflammasome and apoptosis.

ADRENERGIC INPUTS TO THE AMYGDALA AND THE CONTROL OF GONADOTROPHIN RELEASE

1979 ◽  
Vol 90 (3) ◽  
pp. 385-393 ◽  
Author(s):  
José Borrell ◽  
Flavio Piva ◽  
Luciano Martini
Keyword(s):  
Brain Stem ◽  
Dopamine Receptor ◽  
Serum Levels ◽  
Female Rats ◽  
Receptor Blocker ◽  
Dopaminergic Drug ◽  
Gonadotrophin Secretion ◽  
Biphasic Effect ◽  
Adrenergic Blocker ◽  
The Brain

ABSTRACT Drugs able to mimic or to antagonize the action of catecholamines have been implanted bilaterally into the basomedial region of the amygdala of adult castrated female rats. The animals were killed at different intervals after the implantation of the different drugs, and serum levels of LH and FSH were measured by radioimmunoassay. The results have shown that the intra-amygdalar implantation of the alpha-adrenergic blocker phenoxybenzamine induces a significant increase of the release both of LH and FSH. The implantation of the beta-adrenergic blocker propranolol brings about a rise of LH only. The dopamine receptor blocker pimozide stimulates the release of LH and exerts a biphasic effect (stimulation followed by inhibition) of FSH secretion. The alpha-receptor stimulant clonidine and the dopaminergic drug 2-Br-alpha-ergocryptine were without significant effects. From these observations it is suggested that the adrenergic signals reaching the basomedial area of the amygdala (possibly from the brain stem) may be involved in the modulation of gonadotrophin secretion.

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