Pioneering contribution of Professor Bruce Ames to early development in biochemical aspects of oxidatively generated damage to DNA.

The first part of the memorial review article is devoted to a retrospective of selected topics that were the subject of pioneering studies over the period 1985-2025 by Professor Bruce Ames. Major efforts were made to develop accurate and sensitive assays including HPLC coupled with electrochemical detection for monitoring the formation of 8-oxo-7,8-dihydroguanine in isolated cells and animal tissues. Special attention was provided to the minimization of artefactual oxidation of DNA that occurs during sample preparation.

Escalated oxycodone self-administration is associated with expression of voltage gated and calcium activated potassium channels in the mesocorticolimbic system in rats.

Background: The number of individuals diagnosed with opioid use disorder (OUD) has risen steeply because of increased prescribing of opioid drugs including oxycodone for chronic pain relief. When rats given extended access to oxycodone only a subset of animals self-administers more drug over time. Identifying the molecular mechanism associated with this behavior can introduce novel ways to combat OUD.

Escalated Oxycodone Self-Administration Is Associated with Activation of Specific Gene Networks in the Rat Dorsal Striatum.

The diagnosis of opioid use disorder (OUD) is prevalent due to increased prescribing of opioids. Long-term oxycodone self-administration can lead to addiction-like behavioral responses in rats. Herein, we sought to identify molecular pathways consequent to long-term exposure to oxycodone self-administration.

Translin deletion impairs cocaine-induced locomotor sensitization and RGS8 expression in the nucleus accumbens.

Multiple lines of evidence show that the microRNA system plays a prominent role in regulating behavioral responses to psychostimulants. Suppressing microRNA degradation is an effective strategy for elucidating the impact of these intracellular messengers on cellular function. The translin/trax complex is an RNase that appears to mediate degradation of a small number of microRNAs.

RNA sequencing analysis identifies sex differences in transcriptional signatures in the dorsal striatum of female and male rats after withdrawal from methamphetamine self-administration.

Significant methamphetamine (METH)-induced behavioral differences exist between the two sexes of humans and other animals. These dissimilarities may be related to sexual dimorphism in baseline molecular and biochemical mechanisms in brain reward neuroanatomical pathways. As a first step towards identifying sex-based differences in methamphetamine-induced transcriptional signatures, we used RNA sequencing analysis to measure genome-wide changes in gene expression in the dorsal striatum of rats that had self-administered METH.

A Comprehensive 4-Layered In Silico Pharmacogenomics Analysis of the Genetic Addiction Risk Severity (GARS) Test: Strong Genetic Evidence Supporting GARS as a Novel Personalized Pre-Addiction Assessment Tool in the Opioid Crisis Era.

Background: Overdose involving opioids is the black heart of the addiction crisis. "Pre-addiction," as an encouraging concept by NIDA and NIAAA, seems best captured with the construct of dopamine dysregulation. Referring to the abundant publications on "Reward Deficiency Syndrome" (RDS), Genetic Addiction Risk Score (GARS) test, RDSQ29, and KB220, Pre-addiction can be referred to as "reward dysregulation" as a suitable suggestion.

Sex-specific Alterations in the mRNA Expression of Histone Deacetylases (HDACs) in the Rat Brain Following Prolonged Abstinence from Methamphetamine Self-administration.

Methamphetamine (METH) use disorder (MUD) is a psychiatric disease that imposes substantial health burdens throughout the world. Significant sex-specific differences in misuse and relapse rates exist among human METH users and in preclinical models of MUD. We have been using a METH self-administration (SA) model to identify molecular substrates of sex-related behavioral manifestations.

Punishment-Induced Suppression of Methamphetamine Self-Administration Is Accompanied by the Activation of the CPEB4/GLD2 Polyadenylation Complex of the Translational Machinery.

Methamphetamine (METH) use disorder (MUD) is a public health catastrophe. Herein, we used a METH self-administration model to assess behavioral responses to the dopamine receptor D1 (DRD1) antagonist, SCH23390. Differential gene expression was measured in the dorsal striatum after a 30-day withdrawal from METH.

Differentially Expressed Nedd4-binding Protein Ndfip1 Protects Neurons Against Methamphetamine-induced Neurotoxicity.

To identify factors involved in methamphetamine (METH) neurotoxicity, we comprehensively searched for genes which were differentially expressed in mouse striatum after METH administration using differential display (DD) reverse transcription-PCR method and sequent single-strand conformation polymorphism analysis, and found two DD cDNA fragments later identified as mRNA of Nedd4 (neural precursor cell expressed developmentally downregulated 4) WW domain-binding protein 5 (N4WBP5), later named Nedd4 family-interacting protein 1 (Ndfip1). It is an adaptor protein for the binding between Nedd4 of ubiquitin ligase (E3) and target substrate protein for ubiquitination. Northern blot analysis confirmed drastic increases in Ndfip1 mRNA in the striatum after METH injections, and in situ hybridization histochemistry showed that the mRNA expression was increased in the hippocampus and cerebellum at 2 h-2 days, in the cerebral cortex and striatum at 18 h-2 days after single METH administration.

Contribution of oxidation reactions to photo-induced damage to cellular DNA.

This review article is aimed at providing updated information on the contribution of immediate and delayed oxidative reactions to the photo-induced damage to cellular DNA/skin under exposure to UVB/UVA radiations and visible light. Low-intensity UVC and UVB radiations that operate predominantly through direct excitation of the nucleobases are very poor oxidizing agents giving rise to very low amounts of 8-oxo-7,8-dihydroguanine and DNA strand breaks with respect to the overwhelming bipyrimidine dimeric photoproducts. The importance of these two classes of oxidatively generated damage to DNA significantly increases together with a smaller contribution of oxidized pyrimidine bases upon UVA irradiation.

Identification of stress-induced epigenetic methylation onto dopamine D2 gene and neurological and behavioral consequences.

The D2 dopamine receptor () gene has garnered substantial attention as one of the most extensively studied genes across various neuropsychiatric disorders. Since its initial association with severe alcoholism in 1990, particularly through the identification of the allele, numerous international investigations have been conducted to elucidate its role in different conditions. As of February 22, 2024, there are 5485 articles focusing on the gene listed in PUBMED.

Modeling methamphetamine use disorder and relapse in animals: short- and long-term epigenetic, transcriptional., and biochemical consequences in the rat brain.

Methamphetamine use disorder (MUD) is a neuropsychiatric disorder characterized by binge drug taking episodes, intervals of abstinence, and relapses to drug use even during treatment. MUD has been modeled in rodents and investigators are attempting to identify its molecular bases. Preclinical experiments have shown that different schedules of methamphetamine self-administration can cause diverse transcriptional changes in the dorsal striatum of Sprague-Dawley rats.

Modeling methamphetamine use disorder in mammals: Sex differences in behavioral, biochemical, and transcriptional consequences.

Methamphetamine (METH) is the most commonly misused amphetamine-type stimulant throughout the globe. METH is very rewarding, and its misuse can lead to a diagnosis of METH use disorder (MUD). Although METH use is observed in both sexes, there are, however, reported differences in the clinical manifestations of METH use and its consequences.

Incubation of methamphetamine craving in punishment-resistant individuals is associated with activation of specific gene networks in the rat dorsal striatum.

Methamphetamine use disorder (MUD) is characterized by loss of control over compulsive drug use. Here, we used a self-administration (SA) model to investigate transcriptional changes associated with the development of early and late compulsivity during contingent footshocks. Punishment initially separated methamphetamine taking rats into always shock-resistant (ASR) rats that continued active lever pressing and shock-sensitive (SS) rats that reduced their lever pressing.

Neurogenetics and Epigenetics of Loneliness.

Loneliness, an established risk factor for both, mental and physical morbidity, is a mounting public health concern. However, the neurobiological mechanisms underlying loneliness-related morbidity are not yet well defined. Here we examined the role of genes and associated DNA risk polymorphic variants that are implicated in loneliness via genetic and epigenetic mechanisms and may thus point to specific therapeutic targets.

Dopaminergic dysfunction: Role for genetic & epigenetic testing in the new psychiatry.

Reward Deficiency Syndrome (RDS), particularly linked to addictive disorders, costs billions of dollars globally and has resulted in over one million deaths in the United States (US). Illicit substance use has been steadily rising and in 2021 approximately 21.9% (61.

Personalized repetitive transcranial magnetic stimulation (prtms®) for post-traumatic stress disorder (ptsd) in military combat veterans.

Emerging data suggest that post-traumatic stress disorder (PTSD) arises from disrupted brain default mode network (DMN) activity manifested by dysregulated encephalogram (EEG) alpha oscillations. Hence, we pursued the treatment of combat veterans with PTSD (n = 185) using an expanded form of repetitive transcranial magnetic stimulation (rTMS) termed personalized-rTMS (PrTMS). In this treatment methodology spectral EEG based guidance is used to iteratively optimize symptom resolution via (1) stimulation of multiple motor sensory and frontal cortical sites at reduced power, and (2) adjustments of cortical treatment loci and stimulus frequency during treatment progression based on a proprietary frequency algorithm (PeakLogic, Inc.