Maternal immune activation alters fetal and neonatal microglia phenotype and disrupts neurogenesis in mice.

BACKGROUND: Activation of microglia, increase in cortical neuron density, and reduction in GABAergic interneurons are some of the key findings in postmortem autism spectrum disorders (ASD) subjects. The aim of this study was to investigate how maternal immune activation (MIA) programs microglial phenotypes and abnormal neurogenesis in offspring mice. METHODS: MIA was induced by injection of lipopolysaccharide (LPS, i.p.) to pregnant mice at embryonic (E) day 12.5. Microglial phenotypes and neurogenesis were investigated between E15.5 to postnatal (P) day 21 by immunohistochemistry, flow cytometry, and cytokine array. RESULTS: MIA led to a robust increase in fetal and neonatal microglia in neurogenic regions. Homeostatic E15.5 and P4 microglia are heterogeneous, consisting of M1 (CD86+/CD206-) and mixed M1/M2 (CD86+/CD206+)-like subpopulations. MIA significantly reduced M1 but increased mixed M1/M2 microglia, which was associated with upregulation of numerous cytokines with pleotropic property. MIA resulted in a robust increase in Ki67+/Nestin+ and Tbr2+ neural progenitor cells in the subventricular zone (SVZ) of newborn mice. At juvenile stage, a male-specific reduction of Parvalbumin+ but increase in Reelin+ interneurons in the medial prefrontal cortex was found in MIA offspring mice. CONCLUSIONS: MIA programs microglia towards a pleotropic phenotype that may drive excessive neurogenesis in ASD patients. IMPACT: Maternal immune activation (MIA) alters microglial phenotypes in the brain of fetal and neonatal mouse offspring. MIA leads to excessive proliferation and overproduction of neural progenitors in the subventricular zone (SVZ). MIA reduces parvalbumin+ while increases Reelin+ interneurons in the prefrontal cortex. Our study sheds light on neurobiological mechanisms of abnormal neurogenesis in certain neurodevelopmental disorders, such as autism spectrum disorder (ASD).

Role of the NRG1/ErbB4 and PI3K/AKT/mTOR signaling pathways in the anti-psychotic effects of aripiprazole and sertindole in ketamine-induced schizophrenia-like behaviors in rats.

Schizophrenia is a common mental disorder affecting patients' thoughts, behavior, and cognition. Recently, the NRG1/ErbB4 signaling pathway emerged as a candidate therapeutic target for schizophrenia. This study investigates the effects of aripiprazole and sertindole on the NRG1/ErbB4 and PI3K/AKT/mTOR signaling pathways in ketamine-induced schizophrenia in rats. Young male Wistar rats received ketamine (30 mg/kg, intraperitoneally) for 5 consecutive days and aripiprazole (3 mg/kg, orally) or sertindole (2.5 mg/kg, orally) for 14 days. The proposed pathway was investigated by injecting LY294002 (a selective PI3K inhibitor) (25 µg/kg, intrahippocampal injection) 30 min before the drugs. Twenty-four hours after the last injection, animals were subjected to behavioral tests: the open field test, sucrose preference test, novel object recognition task, and social interaction test. Both aripiprazole and sertindole significantly ameliorated ketamine-induced schizophrenic-like behavior, as expected, because of their previously demonstrated antipsychotic activity. Besides, both drugs alleviated ketamine-induced oxidative stress and neurotransmitter level changes in the hippocampus. They also increased the gamma-aminobutyric acid and glutamate levels and glutamate decarboxylase 67 and parvalbumin mRNA expression in the hippocampus. Moreover, aripiprazole and sertindole increased the NRG1 and ErbB4 mRNA expression levels and PI3K, p-Akt, and mTOR protein expression levels. Interestingly, pre-injecting LY294002 abolished all the effects of the drugs. This study reveals that the antipsychotic effects of aripiprazole and sertindole are partly due to oxidative stress reduction as well as NRG1/ErbB4 and PI3K/AKT/mTOR signaling pathways activation. The NRG1/ErbB4 and PI3K signaling pathways may offer a new therapeutic approach for treating schizophrenia in humans.

Selective allergy to conger fish due to parvalbumin

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Reduction of the histamine content and immunoreactivity of parvalbumin in Decapterus maruadsi by a Maillard reaction combined with pressure treatment.

The aim of this study was to develop an effective method for decreasing the content of histamine and the immunoreactivity of parvalbumin in Decapterus maruadsi. As demonstrated by reverse phase high performance liquid chromatography, no effect on histamine content was found when fish were treated by boiling (100 °C), ultrasonication, ultraviolet irradiation, pressure treatment (121 °C, 0.12 MPa). However, the histamine content was reduced by 73.55% when the Maillard reaction was combined with pressure treatment (MPT). Further, the allergenicity of parvalbumin was retained after boiling, ultrasonication and ultraviolet irradiation, but was effectively decreased when fish were treated by MPT. Animal experimental results showed lower levels of IgE, IgG1 and IgG2a and contents of serum histamine when measured in a group of MPT sensitized mice. These results showed that the MPT is an effective method for simultaneously reducing the histamine content and the immunoreactivity of parvalbumin from Decapterus maruadsi.

Cross-reactivity to fish and chicken meat - a new clinical syndrome.

BACKGROUND: Fish is one of the most allergenic foods. While clinical cross-reactivity among different fishes is a widely accepted feature of fish allergy, associations with other food allergies are not well understood. This study aims at analyzing the relevance of clinical cross-reactivity between fish and chicken meat in patients with allergy to chicken meat without sensitization to hen's eggs. METHODS: Patients with food allergy to fish and chicken meat (n = 29) or chicken meat only (n = 7) were recruited. IgE-reactive chicken proteins were identified (Edman, MS analysis) and quantified (ELISA). Allergens were used in IgE ELISA and skin testing. RESULTS: Chicken parvalbumin and two new allergens, aldolase and enolase, were identified at 12, 40, and 50 kDa, respectively. They were recognized by sIgE of 61%, 75%, and 83% of all patient sera which were in the majority of the cases positive for the fish homologues as well. Fish and chicken meat allergens were highly cross-reactive while high inhibition rates with fish or chicken allergens correlated with the patients' primary sensitization to fish or chicken. In cooked or roasted foods, enolase and aldolase were detectable in chicken breast while parvalbumin was detectable in chicken legs and wings. CONCLUSIONS: Fish and chicken meat are cross-reactive foods; both fish-allergic and chicken meat-allergic patients might be at risk of developing a food allergy to chicken meat or to fish, respectively. This clinical phenomenon is proposed to be termed 'fish-chicken syndrome' with cross-reactive allergens involved being parvalbumins, enolases, and aldolases.

Purification and characterization of parvalbumin isotypes from grass carp (Ctenopharyngodon idella).

The prevalence of fish allergy is rapidly increasing because of a growing fish consumption driven mainly by a positive image of the fish and health relationship. The purpose of this study was to characterize parvalbumin isotypes from grass carp (Ctenopharyngodon idella), one of the most frequently consumed freshwater fish in China. Three parvalbumin isotypes were purified using consecutive gel filtration and reverse-phase chromatography and denoted as PVI, PVII, and PVIII. The molecular weights of the isotypes were determined to be 11.968, 11.430, and 11.512 kDa, respectively. PVI showed 74% matched amino acids sequence with PV isotype 4a from Danio rerio, while PVII and PVIII showed 46% matched amino acids sequence with PV isotypes from Hypophthalmichthys molitrix. PVII is the dominant allergen, but it was liable to gastrointestinal enzymes as PVIII; however, PVI was resistant to pepsin digestion. A further study is to characterize the epitopes of PVII, the dominant allergen.

New insights into seafood allergy.

PURPOSE OF REVIEW: Seafood plays an important role in human nutrition worldwide, sustained by international trade of a variety of new seafood products. Increased production and consumption have resulted in more frequent reports of adverse reactions, highlighting the need for more specific diagnosis and treatment of seafood allergy. This review discusses recent literature in this field. RECENT FINDINGS: The most recent prevalence data from Asia highlight seafood as a significant sensitizer in up to 40% of children and 33% of adults. Furthermore, the demonstration of species-specific sensitization to salt-water and fresh-water prawns and processed prawn extract should improve diagnosis. Studies on humans demonstrated for the first time that biologically active fish allergens can be detected in serum samples as early as 10 min after ingestion. These studies highlight that minute amounts of ingested seafood allergens can quickly trigger allergic symptoms; also, inhaled airborne allergens seem to induce sensitization and reactions. In the past 2 years, over 10 additional seafood allergens have been characterized. Allergen-specific detection assays in food products are available for crustacean tropomyosin; however, many specific mollusk and some fish allergens are not readily identified. SUMMARY: Although cross-reactivity between crustacean and mollusks as well as mites is demonstrated, the often poor correlation of IgE reactivity and clinical symptoms calls for more detailed investigations. The recent development of hypoallergenic parvalbumin from carp could form the basis for safer vaccination products for treatment of fish allergy. Molecular characterization of more universal marker allergens for the three major seafood groups will improve current component-resolved clinical diagnosis and have a significant impact on the management of allergic patients, on food labeling and on future immunotherapy for seafood allergy.

Parvalbumin--the major tropical fish allergen.

Fish allergy is common in countries where consumption is high. Asian nations are amongst the world's largest consumers of fish but the allergen profiles of tropical fish are unknown. This study sought to evaluate the allergenicity of four commonly consumed tropical fish, the threadfin (Polynemus indicus), Indian anchovy (Stolephorus indicus), pomfret (Pampus chinensis) and tengirri (Scomberomorus guttatus). Immunoglobulin E (IgE) cross-reactivity with parvalbumin of cod fish (Gad c 1), the major fish allergen, was also studied. Detection of tropical fish and cod specific-IgE was performed by UniCap assay, and skin prick tests were also carried out. The IgE-binding components of tropical fish were identified using IgE immunoblot techniques, and cross-reactivity with Gad c 1 was assessed by ELISA inhibition and IgE immunoblot inhibition. Clinically, nine of 10 patients studied were allergic to multiple fish. All patients exhibited detectable specific-IgE to cod fish (10 of 10 skin prick test positive, eight of 10 UniCap assay positive) despite lack of previous exposure. The major allergen of the four tropical fish was the 12-kDa parvalbumin. IgE cross-reactivity of these allergens to Gad c 1 was observed to be moderate to high in the tropical fish studied. Parvalbumins are the major allergens in commonly consumed tropical fish. They are cross-reactive with each other as well as with Gad c 1. Commercial tests for cod fish appear to be sufficient for the detection of tropical fish specific-IgE.

[Cross reactivity between fish and shellfish]. / Reactividad cruzada entre pescados y mariscos.

In Spain, fish allergy represents 18 % of all cases of food allergy in children while reactions caused by crustacea and mollusks account for 3.8 % and 1.6 % respectively. Cross-reactivity is defined as the recognition of distinct antigens by the same IgE antibody, demonstrable by in vivo and in vitro tests, which clinically manifests as reactions caused by antigens homologous to different species. Subclinical sensitization can also occur, giving rise to patients sensitized to particular fish or shellfish but who do not present symptoms on consumption.Cod and shrimp have been the models used to study allergy to fish and crustacea respectively. The major allergens responsible for cross-reactivity among distinct species of fish and amphibians are proteins that control calcium flow in the muscular sarcoplasm of these animals, called parvalbumins, with a molecular weight of approximately 12 kD and an isoelectric point of 4.75, resistant to the action of heat and enzymatic digestion. Recently, recombinant carp parvalbumin has been reproduced, confirming that this allergen contains 70 % of the IgE epitopes present in natural extract of cod, tuna and salmon, which makes it a valid tool in the diagnosis of patients with fish allergy. Moreover, this recombinant allergen could constitute the basis for the development of immunotherapy against food allergy. In the case of shellfish, a non-taxonomic group that includes crustacea and mollusks, the major allergen is tropomyosin, an essential protein in muscle contraction both in invertebrates and vertebrates. In invertebrates, tropomyosins, which have a molecular weight of between 38 and 41 kD, show great homology in their amino acid sequence and are the panallergens responsible for cross-reactions between crustacea, insects, mites, nematodes, and different classes of mollusks. It is estimated that 50 % of individuals allergic to some type of fish are at risk for reacting to a second species, while those allergic to some type of crustacea present a risk of 75 % due to the greater similarity among tropomyosins than among parvalbumins. In addition, up to 40 % of patients sensitized to one or more fish do not present symptoms on consuming other species, the best tolerated of which belong to the Scombroidea family (which includes tuna).

Purification, biochemical, and immunological characterisation of a major food allergen: different immunoglobulin E recognition of the apo- and calcium-bound forms of carp parvalbumin.

BACKGROUND: Almost 4% of the population suffer from food allergy which is an adverse reaction to food with an underlying immunological mechanism. AIMS: To characterise one of the most frequent IgE defined food allergens, fish parvalbumin. METHODS: Tissue and subcellular distribution of carp parvalbumin was analysed by immunogold electron microscopy and cell fractionation. Parvalbumin was purified to homogeneity, analysed by mass spectrometry and circular dichroism (CD) spectroscopy, and its allergenic activity was analysed by IgE binding and basophil histamine release tests. RESULTS: The isoelectric point (pI) 4.7 form of carp parvalbumin, a three EF-hand calcium-binding protein, was purified to homogeneity. CD analysis revealed a remarkable stability and refolding capacity of calcium-bound parvalbumin. This may explain why parvalbumin, despite cooking and exposure to the gastrointestinal tract, can sensitise patients. Purified parvalbumin reacted with IgE of more than 95% of individuals allergic to fish, induced dose-dependent basophil histamine release and contained, on average, 83% of the IgE epitopes present in other fish species. Calcium depletion reduced the IgE binding capacity of parvalbumin which, according to CD analysis, may be due to conformation-dependent IgE recognition. CONCLUSIONS: Purified carp parvalbumin represents an important cross reactive food allergen. It can be used for in vitro and in vivo diagnosis of fish-induced food allergy. Our finding that the apo-form of parvalbumin had a greatly reduced IgE binding capacity indicates that this form may be a candidate for safe immunotherapy of fish-related food allergy.