Male and female Nrg1 III and control littermates (N = 13-24) were exposed during adulthood to either HFD or standard chow diet (CHOW) for eight weeks before being tested in behavioural domains relevant to schizophrenia.
The clinical characteristics and symptom domains of schizophrenia seemed to be unaffected by the concentrations of vitamin D, BDNF, and NGF, while the NRG1 concentration significantly affected positive symptom domains of schizophrenia (F = 4.927, p = 0.030).
However, since NRG1rs6994992 is not a schizophrenia risk variant in the Han Chinese population, the validated association suggested that ethnic difference may exist in the relationship between NRG1 rs6994992, schizophrenia and creativity.
D2 receptor-mediated miRNA-143 expression is associated with the effects of antipsychotic drugs on phencyclidine-induced schizophrenia-related locomotor hyperactivity and with Neuregulin-1 expression in mice.
Thus, in this study we tested female Nrg1 III transgenic mice using a comprehensive behavioural phenotyping battery relevant to positive, negative and cognitive symptoms of schizophrenia.
Furthermore, Nrg1 III transgenic mice have face validity as they exhibit schizophrenia-relevant behavioral phenotypes including deficits in social preference, impaired fear-associated memory, and reduced prepulse inhibition.
Individuals with a schizophrenia age of onset ⩽25 and a combined allelic load ⩾3 NRG1 risk alleles had significantly larger right (up to 50%, p adj = 0.01) and left (up to 45%, p adj = 0.05) lateral ventricle volumes compared with those with allelic loads of less than three.
Because both neuregulin-1 and ErbB4 are susceptibility genes of schizophrenia and major depression, our study contributes to a better understanding of these disorders.VIDEO ABSTRACT.
Genetic variants of Neuregulin 1 (NRG1) and its neuronal tyrosine kinase receptor ErbB4 are associated with risk for schizophrenia, a neurodevelopmental disorder characterized by excitatory/inhibitory imbalance and dopamine (DA) dysfunction.
They were first implicated in schizophrenia in 2002 with the detection of linkage and association at the NRG1 locus followed after a few years by NRG3.
Numerous genetic and functional studies implicate variants of Neuregulin-1 (NRG1) and its neuronal receptor ErbB4 in schizophrenia and many of its endophenotypes.
These results reinforce the validity of type III Nrg1<sup>+/-</sup> mice for schizophrenia research and suggest that loss of function of type III Nrg1 may not be responsible for the exaggerated response to acute D<sup>9</sup>-THC observed in heterozygous Nrg1 TM mice.
Treatment with NRG1 antibodies that block receptor binding caused behavioral alterations associated with schizophrenia, including, hyper-locomotion and impaired pre-pulse inhibition of startle (PPI).
Therefore, we aimed to evaluate whether glutamatergic variants such as d-amino acid oxidase (<i>DAO</i>), DAO activator (<i>DAOA</i>)/<i>G72</i>, and neuregulin 1 (<i>NRG1</i>) single-nucleotide polymorphisms (SNPs) and their mRNA levels predicted (i) transition to schizophrenia spectrum disorders and (ii) research domain criteria (RDoC) domains, mainly negative valence and cognitive systems.
Investigation of peripheral gene expression patterns of transcripts within the <i>NRG-ErbB</i> signaling pathway, other than neuregulin-1 (<i>NRG1</i>), among patients with schizophrenia and more specifically treatment-resistant schizophrenia (TRS) is limited.
Our review will provide a better understanding of Nrg1 in schizophrenia and a potential strategy for using BACE1 cleavage of Nrg1 as a unique biomarker for diagnosis, as well as a new therapeutic target, of schizophrenia.