Nerve growth factor and its receptor in schizophrenia

Abstract

Promising studies suggest that defects in synaptic plasticity detected in schizophrenia may be linked to neurodevelopmental and neurodegenerative abnormalities and contribute to disease-associated cognitive impairment. We aimed to clarify the role of the synaptic plasticity regulatory proteins, nerve growth factor (NGF) and its receptor (NGFR) in the pathogenesis of schizophrenia by comparative analysis of their blood levels and functional single nucleotide polymorphisms (SNPs) in genes encoding these proteins (NGF and NGFR) in schizophrenia-affected and healthy subjects. Relationships between the selected SNPs' genotypes and NGF and NGFR plasma levels were also assessed. Our results demonstrated a positive association between schizophrenia and the NGF rs6330 as well as the NGFR rs11466155 and rs2072446 SNPs. Also, a negative association between this disorder and NGF rs4839435 as well as NGFR rs734194 was found. In both, haloperidol-treated and antipsychotic-free patients decreased blood levels of the NGF and NGFR were found, and a positive interrelation between rs6330 and rs2072446 carriage and decreased NGF and NGFR levels, respectively, was revealed. In conclusion, our results demonstrate association of schizophrenia with the rs6330, rs4839435 and rs734194, rs11466155, rs2072446 as well as with the decreased blood levels of corresponding proteins. Our findings indicate the implication of alterations in NGFR and NGFR genes in schizophrenia, particularly, in defects of synaptic plasticity. Furthermore, the data obtained suggests that at least in Armenian population the NGF rs6330*T and NGFR rs11466155*T, rs2072446*T alleles might be nominated as risk factors, whereas the NGF rs4839435*A and NGFR rs734194*G alleles might be protective against developing schizophrenia.

Genetic Variations Associated with Brain Disorders: Focus on Synaptic Plasticity and Apoptosis Regulatory Genes in Schizophrenia, Posttraumatic Stress Disorder and Ischemic Stroke

“…Also, it has been shown that chronic cannabis abuse raises NGF serum concentrations in drug-naive patients with SCZ compared to HI [63]. The results of our study demonstrate a positive association between SCZ and the rs6330 SNP of the NGF gene as well as the rs11466155 and rs2072446 SNPs of the NGFR gene [27,28,33]. Also, a negative association between this disorder and rs4839435 SNP of the NGF gene as well as the rs734194 SNP of the NGFR gene was found [27,28,33].…”

“…The results of our study demonstrate a positive association between SCZ and the rs6330 SNP of the NGF gene as well as the rs11466155 and rs2072446 SNPs of the NGFR gene [27,28,33]. Also, a negative association between this disorder and rs4839435 SNP of the NGF gene as well as the rs734194 SNP of the NGFR gene was found [27,28,33]. A non-synonymous rs6330 SNP of the NGF gene is thought to affect intracellular processing and secretion of the NGF protein [64].…”

“…Earlier it was shown that the rs6330 SNP is associated with executive dysfunction in patients with Alzheimer's disease, anxiety related traits and affective disorders [65]. However, study of association between SCZ and the rs6330 SNP of the NGF gene has been performed for the first time by us [27,28,33]. The same applies to the rs4839435 SNP of the NGF gene [27,33].…”

“…However, study of association between SCZ and the rs6330 SNP of the NGF gene has been performed for the first time by us [27,28,33]. The same applies to the rs4839435 SNP of the NGF gene [27,33]. Another polymorphism of the NGF gene, the rs12760036 SNP was shown to associate with susceptibility to SCZ in Korean population, and significant differences in the AG and CA haplotype frequencies in the linkage disequilibrium block within the rs12760036 and rs4839435 SNPs between SCZ patients and HI were found indicating the rs12760036*C minor allele as a risk factor for SCZ in Koreans [66].…”

“…Several studies, including our own, suggest implication of alterations in synaptic neuronal plasticity and apoptosis to pathophysiology of SCZ, PTSD, and IS [10][11][12][13][14][15][16][17][18][19]. This review provides overview of our recent studies (including published [20][21][22][23][24][25][26][27][28][29][30][31][32][33] and unpublished data) on evaluation of potential association of SCZ, PTSD and IS with functional single nucleotide polymorphisms (SNPs) of synaptic plasticity and apoptosis regulatory genes. Here, our attention was focused on genes encoding netrin G1 (NTNG1), brain-derived neurotrophic factor (BDNF), complexin-2 (CPLX2), nerve growth factor (NGF) and its receptor (NGFR), annexin family proteins -annexin A5 and annexin A11 (ANXAV, ANXA11), and B-cell lymphoma 2 (Bcl-2) family proteins -Bcl-2 proper and Bcl-2-associated X protein (BCL2, BAX).…”