Change in gene expression levels of GABA, glutamate and neurosteroid pathways due to acoustic trauma in the cochlea.

The characteristic feature of noise-induced hearing loss (NIHL) is the loss or malfunction of the outer hair cells (OHC) and the inner hair cells (IHC) of the cochlea. 90-95% of the spiral ganglion neurons, forming the cell bodies of cochlear nerve, synapse with the IHCs. Glutamate is the most potent excitatory neurotransmitter for IHC-auditory nerve synapses. Excessive release of glutamate in response to acoustic trauma (AT), may cause excitotoxicity by causing damage to the spiral ganglion neurons (SGN) or loss of the spiral ganglion dendrites, post-synaptic to the IHCs. Another neurotransmitter, GABA, plays an important role in the processing of acoustic stimuli and central regulation after peripheral injury, so it is potentially related to the regulation of hearing function and sensitivity after noise. The aim of this study is to evaluate the effect of AT on the expressions of glutamate excitotoxicity, GABA inhibition and neurosteroid synthesis genes.We exposed 24 BALB/c mice to AT. Controls were sacrificed without exposure to noise, Post-AT(1) and Post-AT(15) were sacrificed on the 1st and 15th day, respectively, after noise exposure. The expressions of various genes playing roles in glutamate, GABA and neurosteroid pathways were compared between groups by real-time PCR.Expressions of Cyp11a1, Gls, Gabra1, Grin2b, Sult1a1, Gad1, and Slc1a2 genes in Post-AT(15) mice were significantly decreased in comparison to control and Post-AT(1) mice. No significant differences in the expression of Slc6a1 and Slc17a8 genes was detected.These findings support the possible role of balance between glutamate excitotoxicity and GABA inhibition is disturbed during the post AT days and also the synthesis of some neurosteroids such as pregnenolone sulfate may be important in this balance.

A heritable profile of six miRNAs in autistic patients and mouse models.

Autism spectrum disorder (ASD) is a group of developmental pathologies that impair social communication and cause repetitive behaviors. The suggested roles of noncoding RNAs in pathology led us to perform a comparative analysis of the microRNAs expressed in the serum of human ASD patients. The analysis of a cohort of 45 children with ASD revealed that six microRNAs (miR-19a-3p, miR-361-5p, miR-3613-3p, miR-150-5p, miR-126-3p, and miR-499a-5p) were expressed at low to very low levels compared to those in healthy controls. A similar but less pronounced decrease was registered in the clinically unaffected parents of the sick children and in their siblings but never in any genetically unrelated control. Results consistent with these observations were obtained in the blood, hypothalamus and sperm of two of the established mouse models of ASD: valproic acid-treated animals and Cc2d1a+/- heterozygotes. In both instances, the same characteristic miRNA profile was evidenced in the affected individuals and inherited together with disease symptoms in the progeny of crosses with healthy animals. The consistent association of these genetic regulatory changes with the disease provides a starting point for evaluating the changes in the activity of the target genes and, thus, the underlying mechanism(s). From the applied societal and medical perspectives, once properly confirmed in large cohorts, these observations provide tools for the very early identification of affected children and progenitors.

Association of Autophagy Gene ATG16L1 Polymorphism with Human Prostate Cancer and Bladder Cancer in Turkish Population

Background: Urological cancers (prostate cancer and bladder cancers) are the most common cancers in Western population and its rate is increasing in the Eastern World. Autophagy has appeared as a fundamental repair mechanism for degrading damaged organelles and proteins. It was clear that autophagy gene polymorphisms are correlated with development of inflammatory bowel disease and it can also be related with prostate cancer (PCa) or bladder cancer (BCa). In this study, we aimed to determine if ATG16L1 (Thr300Ala) polymorphism is associated with an increased risk of developing PCa and BCa and to establish correlations between ATG16L1 genotypes and morphological parameters. Methods: This study included 269 healthy controls and 131 patients (62 PCa and 69 BCa) with PCa and BCa. The ATG16L1 (rs2241880) gene regions were amplified using polymerase chain reaction (PCR), detected by restriction fragment length polymorphism (RFLP). Results: At the end of our research, we found out that the genotype AG was prevalent on patients and controls (34% vs 42%), followed by genotypes AA (35% vs 27%) and GG (31% vs 31%) in PCa. The prevalence of genotypes of AA (wild-type), AG (heterozygous mutant) and GG (homozygous mutant) profiles for the ATG16L1 Thr300Ala polymorphism were 35%, 40% and 25% respectively in BCa patients, and 32%, 40% and 28% respectively in healthy control groups. The G allele frequency was 0.53 for in BCa patients and the control groups. Conclusion: No association was found between ATG16L1 (Thr300Ala) polymorphism and patients with PCa and BCa in Turkish population we studied.