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.

Compulsive methamphetamine self-administration in the presence of adverse consequences is associated with increased hippocampal mRNA expression of cellular adhesion molecules.

Methamphetamine (METH) is a popular but harmful psychostimulant. METH use disorder (MUD) is characterized by compulsive and continued use despite adverse life consequences. METH users experience impairments in learning and memory functions that are thought to be secondary to METH-induced abnormalities in the hippocampus.

Oxidatively generated tandem DNA modifications by pyrimidinyl and 2-deoxyribosyl peroxyl radicals.

Molecular oxygen sensitizes DNA to damage induced by ionizing radiation, Fenton-like reactions, and other free radical-mediated reactions. It rapidly converts carbon-centered radicals within DNA into peroxyl radicals, giving rise to a plethora of oxidized products consisting of nucleobase and 2-deoxyribose modifications, strand breaks and abasic sites. The mechanism of formation of single oxidation products has been extensively studied and reviewed.

Practical Aspects in the Study of Biological Photosensitization Including Reaction Mechanisms and Product Analyses: A Do's and Don'ts Guide.

The interaction of light with natural matter leads to a plethora of photosensitized reactions. These reactions cause the degradation of biomolecules, such as DNA, lipids, proteins, being therefore detrimental to the living organisms, or they can also be beneficial by allowing the treatment of several diseases by photomedicine. Based on the molecular mechanistic understanding of the photosensitization reactions, we propose to classify them in four processes: oxygen-dependent (type I and type II processes) and oxygen-independent [triplet-triplet energy transfer (TTET) and photoadduct formation].

Compulsive drug-taking is associated with habenula-frontal cortex connectivity.

As a critical node connecting the forebrain with the midbrain, the lateral habenula (LHb) processes negative feedback in response to aversive events and plays an essential role in value-based decision-making. Compulsive drug use, a hallmark of substance use disorder, is attributed to maladaptive decision-making regarding aversive drug-use-related events and has been associated with dysregulation of various frontal-midbrain circuits. To understand the contributions of frontal-habenula-midbrain circuits in the development of drug dependence, we employed a rat model of methamphetamine self-administration (SA) in the presence of concomitant footshock, which has been proposed to model compulsive drug-taking in humans.

Biochemical Neuroadaptations in the Rat Striatal Dopaminergic System after Prolonged Exposure to Methamphetamine Self-Administration.

Perturbations in striatal dopamine (DA) homeostasis might underlie the behavioral and pathobiological consequences of METH use disorder in humans. To identify potential consequences of long-term METH exposure, we modeled the adverse consequence DSM criterion of substance use disorders by giving footshocks to rats that had escalated their intake of METH during a drug self-administration procedure. Next, DA D1 receptor antagonist, SCH23390 was injected.

Dopaminylation in Psychostimulant Use Disorder Protects Against Psychostimulant Seeking Behavior by Normalizing Nucleus Accumbens (NAc) Dopamine Expression.

Background: Repeated cocaine administration changes histone acetylation and methylation on Lys residues and Deoxyribonucleic acid (DNA) within the nucleus accumbens (NAc). Recently Nestler's group explored histone Arg (R) methylation in reward processing models. Damez-Werno (2016) reported that during human investigations and animal self-administration experiments, the histone mark protein-R-methyltransferase-6 (PRMT6) and asymmetric dimethylation of R2 on histone H3 (H3R2me2a) decreased in the rodent and cocaine-dependent human NAc.