BDNF (Val66Met) Genetic Polymorphism is Associated with Vulnerability for Methamphetamine Dependence

Iamjan, Sri-arun; Thanoi, Samur; Watiktinkorn, Paritat; Nudmamud-Thanoi, Sutisa; Reynolds, Gavin P.

doi:10.2217/pgs.15.96

Cited by 26 publications

(23 citation statements)

References 27 publications

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“…3), more importantly, our data showed that BDNF expression levels in midbrain tissue is significantly less abundant in DAT-Smo ko mice compared to wt mice after repeated methamphetamine sensitization treatment. Since BDNF is thought to play critical roles in regulation of addictive behavior and behavioral responses to psychostimulants such as methamphetamine (Bousman et al, 2009; Iamjan et al, 2015; Itoh et al, 2005; Manning et al, 2015; Manning and van den Buuse, 2013; Sim et al, 2010), its alteration by smo deletion in DA neurons might account for the behavioral differences we observed in DAT-Smo ko mice. A recent study showed that DAT-Shh ko mice have altered GDNF expression in striatum, which suggested reciprocal, trophic factor signaling between mesencephalic DA and striatal acetylcholine (Ach) and fast-spiking (FS) GABAergic neurons (Gonzalez-Reyes et al, 2012).…”

Section: Discussion/conclusionmentioning

confidence: 92%

“…Gene expression analysis showed decreased gene expression for smo (p=0.001, Student's t-test) and Gli 1 (known target gene of smo, p=0.009, Student's t-test) in DAT-Smo ko mice, confirming the DA specific deletion of smo gene and alteration in the shh-smo-Gli1 signaling pathway in the ventral midbrain (Fig 7A). Brain-derived neurotrophic factor (BDNF) has been implicated in DA system function, including addiction and responses to METH (Bousman et al, 2009; Iamjan et al, 2015; Itoh et al, 2005; Manning et al, 2015; Manning and van den Buuse, 2013; Sim et al, 2010), and has recently been identified as a potential target gene for the shh pathway in smooth muscle cells (Radzikinas et al, 2011). To examine whether it is also regulated by shh signaling in dopaminergic neurons, we examined the mRNA levels of BDNF in ventral midbrain tissues from wt and DAT-Smo ko mice.…”

Section: Resultsmentioning

confidence: 99%

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Effect of the sonic hedgehog receptor smoothened on the survival and function of dopaminergic neurons

Zhou

Pace

Filichia

et al. 2016

Experimental Neurology

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Objective To determine the influence of the sonic hedgehog (shh) pathway and its receptor smoothened (smo), on the survival and functionality of dopaminergic (DA) neurons. Background During early development, shh induces the differentiation of DA neurons. However, it is unknown whether shh signaling is required in the maturation or maintenance of DA neurons during later development and adulthood due to the lethality of traditional shh knockout models. Methods We utilized the cre-loxP system to achieve late developmental stage and cell type-specific deletion of the shh receptor, smo, in DA neurons by crossing DATcre (dopamine transporter) mice with SmoloxP/loxP mice. We assessed for differences between knockout (ko) and wildtype (wt) mice using combined histochemistry, gene expression analysis, and behavioral evaluation. Number and size of DA neurons in ventral midbrain and the DA neural terminal density in striatum were measured using unbiased stereological quantification. The survival of DA neurons under neurotoxin challenge was examined in the unilateral 6-hydroxydopamine (6-OHDA) Parkinson's disease animal model and the more subtle function under challenge of the dopaminergic system was examined by methamphetamine single- and repeated challenge in wt and ko mice. Results Tyrosine hydroxylase (TH) positive neuronal counts and neuronal size in substantia nigra (SN) and ventral tegmental area (VTA) showed no difference between wt and DAT-Smo ko mice in young (5 months) or aged (22 months) mice. There was also no difference in the striatal DA projections between wt and ko mice in both age groups. In unilateral striatal 6-OHDA lesions modeling Parkinson's disease, using stereotaxic injection of 6-OHDA intrastriatally led to loss of dopaminergic neurons in SN and diminished TH positive projections in striatum. However, there was no differences in survival of DA neurons between wt and ko mice. DAT-Smo ko mice demonstrated hyperactivity compared to wt mice at 5 months, but showed no difference in activity at 22 months. When injected with a one-time bolus of methamphetamine (METH), despite the higher basal locomotion activity, DAT-Smo ko mice showed a diminished response to a single METH challenge. In METH sensitization testing, ko mice showed decreased sensitization compared to wt mice without evidence of a delayed shift in dynamics of sensitization. Gene expression analysis showed decreased gene expression of smo, Gli 1 (known target gene of smo) and BDNF (brain-derived neurotrophic factor) in the SN. Gene expression was not altered in striatum for the genes examined in this study including dopamine receptor genes, neurotropic genes such as Glial cell line-derived neurotrophic factor (GDNF), and bone morphogenetic protein 7 (BMP7). Conclusion Our study showed the smo receptor function is not required for the maturation and survival of DA neurons during late development, aging or under stress challenge. However, smo function has an influence on behavior in young adult mice and in responses of mice to a drug ...

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Section: Discussion/conclusionmentioning

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Effect of the sonic hedgehog receptor smoothened on the survival and function of dopaminergic neurons

Zhou

Pace

Filichia

et al. 2016

Experimental Neurology

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“…Third, we only analyzed four SNPs of GRIN2B gene. In a male Thai population, 35,36 rs1126442 of gene GRIN1 and rs6265 of gene BDNF were shown to have an association with methamphetamine dependence. Besides, rs17189632 of gene GRIN3A and rs2240158 of gene GRIN3B may contribute to the susceptibility of heroin addiction.…”

Section: Discussionmentioning

confidence: 96%

GRIN2B Gene Polymorphism in Chronic Ketamine Users

et al. 2020

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Background and Objectives We examined the allelic variants of N‐methyl‐ d‐aspartate receptor 2B (GRIN2B) and analyzed the associations between GRIN2B gene polymorphism with ketamine use conditions and psychopathological symptoms in chronic ketamine users. Methods A total of 231 subjects were recruited. Four single nucleotide polymorphisms of GRIN2B, rs1805502, rs7301328, rs890, and rs1806201 were examined in 151 male chronic ketamine users and 80 controls. Psychopathological symptoms in chronic ketamine users were evaluated using the Positive and Negative Syndrome Scale, the Beck Depression Inventory, and the Beck Anxiety Inventory. Results The genotype CC of rs1806201 had a lower frequency in ketamine users than that in control subjects (χ2 = 8.167, P = .004) and the T allele frequency of rs1806201 in ketamine users was higher than that in the control subjects (P = .009, odds ratio = 2.019 [1.196‐3.410]). Ketamine users of genotype TT and CC of rs1806201 had an earlier onset of ketamine use than subjects of genotype TC (P = .038, P = .049, respectively). The dose of ketamine consumption per day of use was higher in genotype GG of rs7301328 than that in those with CG in ketamine users (P = .026). There were no significant differences of the severity of psychopathologic symptoms among different genotypes tested. Conclusion and Scientific Significance GRIN2B gene polymorphism may play a role in ketamine abuse. (Am J Addict 2020;29:105–110)

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“…The blood samples from the cubital vein were collected in EDTA blood collection tube and the genomic DNA was extracted from blood leukocytes by using Trizol LS reagent following by the manufacturing instruction. The fingertip blood samples were collected on FTA cards and the DNA extraction was performed following a previous report 19. The genotyping of COMT Val 158 Met SNP (rs4680) was conducted by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method.…”

Section: Methodsmentioning

confidence: 99%

Association study of the functional Catechol-O-Methyltranferase (COMT) Val¹⁵⁸Met polymorphism on executive cognitive function in a Thai sample

et al. 2019

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Catechol-O-Methyltranferase (COMT) plays a crucial role in the removal of cortical dopamine and is strongly implicated in human executive function. Numerous studies have reported associations of the COMT Val158Met (rs4680) polymorphism with executive function in healthy subjects. However, little work has investigated this in the Thai population and the relationship of age and education with this association remains unclear. Therefore, this study was designed to investigate the association of this polymorphism of the COMT gene with executive cognitive brain function in healthy subjects and the relationship with age and education. The Wisconsin Card Sorting Test (WCST) was performed to assess executive function in 254 healthy Thai subjects (aged 20-72 years). The results showed a significant association of rs4680 with executive function, in which Val/Met heterozygotes demonstrated better cognitive set shifting performance. Moreover, Met allele carriers showed a significantly stronger effect in the categories completed score than did Val homozygotes. Furthermore, age and education also showed a significant association with COMT genotype and WCST. These results revealed that executive cognitive function is associated with COMT genotype and influenced by age and/or education level in a Thai sample.

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BDNF (Val66Met) Genetic Polymorphism is Associated with Vulnerability for Methamphetamine Dependence

Abstract: The present findings indicate that rs6265 is associated with METH dependence in the Thai population, with the GG genotype greater in METH-dependent subjects but reducing the emergence of METH-dependent psychosis.

Cited by 26 publications

References 27 publications

Effect of the sonic hedgehog receptor smoothened on the survival and function of dopaminergic neurons

Effect of the sonic hedgehog receptor smoothened on the survival and function of dopaminergic neurons

GRIN2B Gene Polymorphism in Chronic Ketamine Users

Association study of the functional Catechol-O-Methyltranferase (COMT) Val¹⁵⁸Met polymorphism on executive cognitive function in a Thai sample

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BDNF (Val66Met) Genetic Polymorphism is Associated with Vulnerability for Methamphetamine Dependence

Abstract: The present findings indicate that rs6265 is associated with METH dependence in the Thai population, with the GG genotype greater in METH-dependent subjects but reducing the emergence of METH-dependent psychosis.

Cited by 26 publications

References 27 publications

Effect of the sonic hedgehog receptor smoothened on the survival and function of dopaminergic neurons

Effect of the sonic hedgehog receptor smoothened on the survival and function of dopaminergic neurons

GRIN2B Gene Polymorphism in Chronic Ketamine Users

Association study of the functional Catechol-O-Methyltranferase (COMT) Val158Met polymorphism on executive cognitive function in a Thai sample

Contact Info

Product

Resources

About

Association study of the functional Catechol-O-Methyltranferase (COMT) Val¹⁵⁸Met polymorphism on executive cognitive function in a Thai sample