Anti-Tyrosine Hydroxylase monoclonal antibody, clone MOD2 [Alexa Fluor® 488]

Dinotefuran (DIN) belongs to the neonicotinoids (NNs), a class of globally applied pesticides originally developed to exhibit selective toxicity in insects. However, several reports have suggested that NNs also exert neurotoxic effects in mammals. We previously demonstrated neurobehavioral effects of DIN on mice under non-stressful conditions. For further toxicity assessments in the present study, we investigated the effects of DIN on mice exposed to stressful conditions. After subacutely administering a no-observed-effect-level (NOEL) dose of DIN and/or chronic unpredictable mild stress (CUMS) to mice, we conducted three behavioral tests (i.e., open field test [OFT], tail suspension test [TST] and forced swimming test [FST]). In addition, serotonin (5-HT) and tryptophan hydroxylase 2 (TPH2) of the dorsal raphe nuclei (DRN) and median raphe nuclei (MRN) and tyrosine hydroxylase (TH) of the ventral tegmental area and substantia nigra (SN) were evaluated immunohistochemically. A NOEL dose of DIN or CUMS alone increased of the total distance in OFT, decreased or increased the immobility time in TST or FST, respectively, and increased the positive intensity of 5-HT and TPH2 in the DRN/MRN, and TH in the SN. These changes were suppressed under the conditions of combined exposure to DIN and CUMS, though the blood corticosterone level was increased depending on the blood DIN values and the presence of CUMS. The present study suggests the multifaceted toxicity of the neurotoxin DIN.

Purpose: To elucidate the genetic basis of drug addiction by conducting a genetic analysis of TH (tyrosine hydroxylase) gene and the novel polymorphisms that might help in understanding addiction and its molecular basis. Methods: Forty-two subjects were recruited into three groups for this study. DNA was isolated from the individuals. PCR amplification of TH gene was carried out and amplicons were sequenced. Genomic characterization of TH gene provided five polymorphic loci - TH 1, TH 2, TH 3, TH 4 and TH 5 which were found among all the groups. Results: According to Shannon's diversity index, the studied population was between 0.0762 and 0.6032. Heterozygosity index depicted that TH 1 locus was less heterozygous (0.3288), followed by TH 5 (0.3152). TH 1 (0.1462) was the least heterozygous. Genotypic analysis predicted that among these five loci, TH 4 (p = 0.039898) and TH 2 (p = 0.851716) were non-significant (p > 0.05) and obeyed Hardy Weinberg Equilibrium (HWE) law. There are few genetic changes in the studied population that can statistically be associated with drug addiction. Still, their genotypic distribution in the gene pool was very low. Conclusion: On the basis of these findings, drug addiction in the studied population is more likely a social issue rather than a genetic one.