Induction of inducible nitric oxide synthase expression in activated microglia and astrocytes following pre- and postnatal immune challenge in an animal model of schizophrenia

Esshili, Awatef; Manitz, Marie-Pierre; Freund, Nadja; Juckel, Georg

doi:10.1016/j.euroneuro.2020.04.002

Cited by 20 publications

(13 citation statements)

References 54 publications

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“…Consistent with this, maternal LPS administration accentuates offspring astrogliosis in the hippocampus, cortex, amygdala, hypothalamus, thalamus, and white matter, associated with hypomyelination [87][88][89][90][91]. Likewise, long-lasting astrogliosis takes place in the hippocampus of mice prenatally exposed to the human influenza virus [92], and similar findings have been observed following poly (I:C)-induced maternal immune activation [93][94][95][96]. Despite the latter, other studies have described that prenatal poly (I:C) exposure does not affect the astroglial number and expression of GFAP in the offspring [97][98][99][100].…”

Section: Maternal Inflammation and Its Impact On Astrocytessupporting

confidence: 69%

Astroglial Hemichannels and Pannexons: The Hidden Link between Maternal Inflammation and Neurological Disorders

Prieto-Villalobos

Alvear

Liberona

et al. 2021

IJMS

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Maternal inflammation during pregnancy causes later-in-life alterations of the offspring’s brain structure and function. These abnormalities increase the risk of developing several psychiatric and neurological disorders, including schizophrenia, intellectual disability, bipolar disorder, autism spectrum disorder, microcephaly, and cerebral palsy. Here, we discuss how astrocytes might contribute to postnatal brain dysfunction following maternal inflammation, focusing on the signaling mediated by two families of plasma membrane channels: hemi-channels and pannexons. [Ca2+]i imbalance linked to the opening of astrocytic hemichannels and pannexons could disturb essential functions that sustain astrocytic survival and astrocyte-to-neuron support, including energy and redox homeostasis, uptake of K+ and glutamate, and the delivery of neurotrophic factors and energy-rich metabolites. Both phenomena could make neurons more susceptible to the harmful effect of prenatal inflammation and the experience of a second immune challenge during adulthood. On the other hand, maternal inflammation could cause excitotoxicity by producing the release of high amounts of gliotransmitters via astrocytic hemichannels/pannexons, eliciting further neuronal damage. Understanding how hemichannels and pannexons participate in maternal inflammation-induced brain abnormalities could be critical for developing pharmacological therapies against neurological disorders observed in the offspring.

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Section: Maternal Inflammation and Its Impact On Astrocytessupporting

confidence: 69%

Astroglial Hemichannels and Pannexons: The Hidden Link between Maternal Inflammation and Neurological Disorders

Prieto-Villalobos

Alvear

Liberona

et al. 2021

IJMS

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“…As a practical contribution to the BPC 157/ketamine relation, we noted a considerable overlapping of gene overexpression as an apparent close connection between the ketamine and BPC 157 (the highest ketamine dose 30 mg/kg ip vs. lowest BPC 157 10 ng/kg ip dose) ( Figure 11 ). This was done with the genes’ expression analysis in brain tissue, using Nos1 [ 34 , 35 ], Nos2 [ 36 , 37 ], Nos3 [ 38 ], Plcg1 [ 39 , 40 ], Prkcg [ 41 , 42 ], Ptgs2 [ 43 ], and Ptk2 [ 44 , 45 ], all associated with schizophrenia presentation. We identified the similar overexpression of the genes in the healthy rats treated with the ketamine ( Nos1 , Nos2 , Plcg1 , Prkcg , Ptgs2 , and Ptk2 ) and in the BPC 157 ( Nos1 , Nos2 , Plcg1 , Prkcg , and Ptk2 ), thus a considerable overlapping of gene overexpression.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, to minimize at least partly the limitations known in the prime behavioral studies and to highlight a likely special point to explain how the dysfunction and its counteraction is causal to or the result of ketamine/BPC 157 interactions, a particular gene expression was carried out in the brain, providing their particular association with schizophrenia conditions. Analyzed [ 33 ] were Nos1 [ 34 , 35 ], Nos2 [ 36 , 37 ], Nos3 [ 38 ], phospholipase C, gamma 1 ( Plcg1 ) [ 39 , 40 ], protein kinase C gamma ( Prkcg ) [ 41 , 42 ], prostaglandin-endoperoxide synthase 2, cyclooxygenase (Cox)2 ( Ptgs2 ) [ 43 ], and protein tyrosine kinase 2 ( Ptk2 ) [ 44 , 45 ].…”

Section: Introductionmentioning

confidence: 99%

BPC 157, L-NAME, L-Arginine, NO-Relation, in the Suited Rat Ketamine Models Resembling “Negative-Like” Symptoms of Schizophrenia

et al. 2022

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We attempted throughout the NO-system to achieve the particular counteraction of the ketamine-induced resembling “negative-like” schizophrenia symptoms in rats using pentadecapeptide BPC 157, and NO-agents, NG-nitro-L-arginine methylester (L-NAME), and/or L-arginine, triple application. This might be the find out the NO-system organized therapy (i.e., simultaneously implied NO-system blockade (L-NAME) vs. NO-system over-stimulation (L-arginine) vs. NO-system immobilization (L-NAME+L-arginine)). The ketamine regimen (intraperitoneally/kg) included: 3 mg (cognitive dysfunction, novel object recognition test), 30 mg (anxiogenic effect (open field test) and anhedonia (sucrose test)), and 8 mg/3 days (social withdrawal). Medication (mg/kg intraperitoneally) was L-NAME (5), L-arginine (100), and BPC 157 (0.01), alone and/or together, given immediately before ketamine (L-NAME, L-arginine, and combination) or given immediately after (BPC 157 and combinations). BPC 157 counteracted ketamine-cognition dysfunction, social withdrawal, and anhedonia, and exerted additional anxiolytic effect. L-NAME (antagonization, social withdrawal) and L-arginine (antagonization, cognitive dysfunction, anhedonia) both included worsening cognitive dysfunction, anhedonia, and anxiogenic effect (L-NAME), social withdrawal, and anxiogenic effect (L-arginine). Thus, ketamine-induced resembling “negative-like” schizophrenia symptoms were “L-NAME non-responsive, L-arginine responsive” (cognition dysfunction), “L-NAME responsive, L-arginine non-responsive” (social withdrawal), “L-NAME responsive, L-arginine responsive, opposite effect” (anhedonia) and “L-NAME responsive, L-arginine responsive, parallel effect” (both anxiogening). In cognition dysfunction, BPC 157 overwhelmed NO-agents effects. The mRNA expression studies in brain tissue evidenced considerable overlapping of gene overexpression in healthy rats treated with ketamine or BPC 157. With the BPC 157 therapy applied immediately after ketamine, the effect on Nos1, Nos2, Plcg1, Prkcg, and Ptgs2 (increased or decreased expression), appeared as a timely specific BPC 157 effect on ketamine-specific targets.

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“…Aβ stimulates NF-κB and complement signaling in astrocytes, which may induce the synthesis of inflammatory mediators by astrocytes and impair synaptic density and dendritic morphology [ 57 , 58 ], responsible for neurodegenerative changes in AD. Astrocytes cause nitric oxide (NO)-mediated neurotoxicity by increasing the expression of inducible nitric oxide synthase (iNOS) and contribute to sustained neuroinflammation [ 59 ]. Additionally, the astrocyte A1 phenotype is known to cause nerve damage by enhancing the classical C3 factor [ 53 ].…”

Section: Microglia and Astrocytesmentioning

confidence: 99%

Microglia and Astrocytes in Alzheimer’s Disease in the Context of the Aberrant Copper Homeostasis Hypothesis

et al. 2021

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Evidence of copper’s (Cu) involvement in Alzheimer’s disease (AD) is available, but information on Cu involvement in microglia and astrocytes during the course of AD has yet to be structurally discussed. This review deals with this matter in an attempt to provide an updated discussion on the role of reactive glia challenged by excess labile Cu in a wide picture that embraces all the major processes identified as playing a role in toxicity induced by an imbalance of Cu in AD.

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Induction of inducible nitric oxide synthase expression in activated microglia and astrocytes following pre- and postnatal immune challenge in an animal model of schizophrenia

Cited by 20 publications

References 54 publications

Astroglial Hemichannels and Pannexons: The Hidden Link between Maternal Inflammation and Neurological Disorders

Astroglial Hemichannels and Pannexons: The Hidden Link between Maternal Inflammation and Neurological Disorders

BPC 157, L-NAME, L-Arginine, NO-Relation, in the Suited Rat Ketamine Models Resembling “Negative-Like” Symptoms of Schizophrenia

Microglia and Astrocytes in Alzheimer’s Disease in the Context of the Aberrant Copper Homeostasis Hypothesis

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