Synaptogyrin-3 Prevents Cocaine Addiction and Dopamine Deficits.

Synaptogyrin-3, a functionally obscure synaptic vesicle protein, interacts with vesicular monoamine and dopamine transporters, bringing together dopamine release and reuptake sites. Synaptogyrin-3 was reduced by chronic cocaine exposure in both humans and rats, and synaptogyrin-3 levels inversely correlated with motivation to take cocaine in rats. Synaptogyrin-3 overexpression in dopamine neurons reduced cocaine self-administration, decreased anxiety-like behavior, and enhanced cognitive flexibility.

Stability of Per- and Polyfluoroalkyl Substances in Solvents Relevant to Environmental and Toxicological Analysis.

Per- and polyfluoroalkyl substances (PFASs) are widely used anthropogenic chemicals. For environmental and toxicological analysis, it is important to understand the stability of PFASs, including novel per- and polyfluoroalkyl ether acids (PFEAs), in commonly used solvents. In this study, we investigated the effects of PFAS characteristics, solvent type, water-to-organic solvent ratio, and temperature on the stability of 21 PFASs including 18 PFEAs.

Chronic Ethanol Differentially Modulates Glutamate Release from Dorsal and Ventral Prefrontal Cortical Inputs onto Rat Basolateral Amygdala Principal Neurons.

The medial prefrontal cortex (mPFC) and the basolateral amygdala (BLA) have strong reciprocal connectivity. Projections from the BLA to the mPFC can drive innate, anxiety-related behaviors, but it is unclear whether reciprocal projections from the mPFC to BLA have similar roles. Here, we use optogenetics and chemogenetics to characterize the neurophysiological and behavioral alterations produced by chronic ethanol exposure and withdrawal on dorsal mPFC (dmPFC) and ventral mPFC (vmPFC) medial prefrontal cortical terminals in the BLA.

Synergistic Phytotoxic Effects of Culmorin and Trichothecene Mycotoxins.

Species of the fungus cause Fusarium head blight (FHB) of cereal crops and contaminate grain with sesquiterpenoid mycotoxins, including culmorin (CUL) and trichothecenes. While the phytotoxicity of trichothecenes, such as deoxynivalenol (DON), and their role in virulence are well characterized, less is known about the phytotoxicity of CUL and its role in the development of FHB. Herein, we evaluated the phytotoxic effects of purified CUL and CUL-trichothecene mixtures using growth and (wheat) root elongation assays.

Requirement of Two Acyltransferases for 4- O-Acylation during Biosynthesis of Harzianum A, an Antifungal Trichothecene Produced by Trichoderma arundinaceum.

Trichothecenes are sesquiterpenoid toxins produced by multiple fungi, including plant pathogens, entomopathogens, and saprotrophs. Most of these fungi have the acyltransferase-encoding gene tri18. Even though its function has not been determined, tri18 is predicted to be involved in trichothecene biosynthesis because of its pattern of expression and its location near other trichothecene biosynthetic genes.

Role of Trichoderma arundinaceum tri10 in regulation of terpene biosynthetic genes and in control of metabolic flux.

Production of trichothecene toxins occurs in phylogenetically diverse fungi with different lifestyles. In these fungi, most homologs of the trichothecene biosynthetic gene cluster include the transcription factor genes tri6 and tri10. Analyses of phytopathogenic species of Fusarium indicate that the TRI6 and TRI10 proteins positively regulate genes required for synthesis of trichothecenes as well as farnesyl diphosphate (FPP), a precursor of the trichothecene and other terpenoids (e.

Chronic Social Isolation Stress during Peri-Adolescence Alters Presynaptic Dopamine Terminal Dynamics via Augmentation in Accumbal Dopamine Availability.

Chronic peri-adolescent stress in humans increases risk to develop a substance use disorder during adulthood. Rats reared in social isolation during peri-adolescence (aSI; 1 rat/cage) period show greater ethanol and cocaine intake compared to group housed (aGH; 4 rats/cage) rats. In addition, aSI rats have a heightened dopamine response in the nucleus accumbens (NAc) to rewarding and aversive stimuli.

Effect of deletion of a trichothecene toxin regulatory gene on the secondary metabolism transcriptome of the saprotrophic fungus Trichoderma arundinaceum.

Trichothecenes are terpenoid toxins produced by multiple fungal species with diverse lifestyles. In these fungi, the trichothecene biosynthetic gene (tri) cluster includes a gene encoding a CysHis Zn-finger protein (TRI6). Analyses of plant pathogenic Fusarium species indicate that tri6 regulates tri gene expression.

SNARE Complex-Associated Proteins in the Lateral Amygdala of Macaca mulatta Following Long-Term Ethanol Drinking.

Background: Recent work with long-term ethanol (EtOH) self-administration in nonhuman primate models has revealed a complex array of behavioral and physiological effects that closely mimic human alcohol abuse. Detailed neurophysiological analysis in these models suggests a myriad of pre- and postsynaptic neurobiological effects that may contribute to the behavioral manifestations of long-term EtOH drinking. The molecular mechanisms regulating presynaptic effects of this chronic EtOH exposure are largely unknown.

Evolution of structural diversity of trichothecenes, a family of toxins produced by plant pathogenic and entomopathogenic fungi.

Trichothecenes are a family of terpenoid toxins produced by multiple genera of fungi, including plant and insect pathogens. Some trichothecenes produced by the fungus Fusarium are among the mycotoxins of greatest concern to food and feed safety because of their toxicity and frequent occurrence in cereal crops, and trichothecene production contributes to pathogenesis of some Fusarium species on plants. Collectively, fungi produce over 150 trichothecene analogs: i.

Ethanol Mediated Inhibition of Synaptic Vesicle Recycling at Amygdala Glutamate Synapses Is Dependent upon Munc13-2.

Chronic exposure to alcohol produces adaptations within the basolateral amygdala (BLA) that are associated with the development of anxiety-like behaviors during withdrawal. In part, these adaptations are mediated by plasticity in glutamatergic synapses occurring through an AMPA receptor mediated form of post-synaptic facilitation in addition to a unique form of presynaptic facilitation. In comparison to the post-synaptic compartment, relatively less is understood about the mechanisms involved in the acute and chronic effects of ethanol in the presynaptic terminal.

Differential Expression of Munc13-2 Produces Unique Synaptic Phenotypes in the Basolateral Amygdala of C57BL/6J and DBA/2J Mice.

Unlabelled: C57BL/6J (B6) and DBA/2J (D2) mice are well known to differentially express a number of behavioral phenotypes, including anxiety-like behavior, fear conditioning, and drug self-administration. However, the cellular mechanisms contributing to these differences remain unclear. Given the basolateral amygdala (BLA) contributes to these behaviors, we characterized strain-dependent differences in presynaptic and postsynaptic function in BLA neurons by integrating electrophysiological, biochemical, and genetic approaches to identify specific molecular mechanisms.

Trichothecenes and aspinolides produced by Trichoderma arundinaceum regulate expression of Botrytis cinerea genes involved in virulence and growth.

Trichoderma arundinaceum (Ta37) and Botrytis cinerea (B05.10) produce the sesquiterpenoids harzianum A (HA) and botrydial (BOT), respectively. TaΔTri5, an HA non-producer mutant, produces high levels of the polyketide compounds aspinolides (Asp) B and C.

Acute and chronic ethanol exposure differentially regulate CB1 receptor function at glutamatergic synapses in the rat basolateral amygdala.

The endogenous cannabinoid (eCB) system has been suggested to play a key role in ethanol preference and intake, the acute effects of ethanol, and in the development of withdrawal symptoms following ethanol dependence. Ethanol-dependent alterations in glutamatergic signaling within the lateral/basolateral nucleus of the amygdala (BLA) are critical for the development and expression of withdrawal-induced anxiety. Notably, the eCB system significantly regulates both glutamatergic and GABAergic synaptic activity within the BLA.

Botrydial and botcinins produced by Botrytis cinerea regulate the expression of Trichoderma arundinaceum genes involved in trichothecene biosynthesis.

Trichoderma arundinaceum IBT 40837 (Ta37) and Botrytis cinerea produce the sesquiterpenes harzianum A (HA) and botrydial (BOT), respectively, and also the polyketides aspinolides and botcinins (Botcs), respectively. We analysed the role of BOT and Botcs in the Ta37-B. cinerea interaction, including the transcriptomic changes in the genes involved in HA (tri) and ergosterol biosynthesis, as well as changes in the level of HA and squalene-ergosterol.

Chronic social isolation during adolescence augments catecholamine response to acute ethanol in the basolateral amygdala.

Adolescent social isolation (SI) results in numerous behavioral alterations associated with increased risk of alcoholism. Notably, many of these changes involve the basolateral amygdala (BLA), including increased alcohol seeking. The BLA sends a strong glutamatergic projection to the nucleus accumbens and activation of this pathway potentiates reward-seeking behavior.

Novel aspinolide production by Trichoderma arundinaceum with a potential role in Botrytis cinerea antagonistic activity and plant defence priming.

Harzianum A (HA), a trichothecene produced by Trichoderma arundinaceum, has recently been described to have antagonistic activity against fungal plant pathogens and to induce plant defence genes. In the present work, we have shown that a tri5 gene-disrupted mutant that lacks HA production overproduces two polyketides, aspinolides B and C, which were not detected in the wild-type strain. Furthermore, four new aspinolides (D-G) were characterized.

Production of trichodiene by Trichoderma harzianum alters the perception of this biocontrol strain by plants and antagonized fungi.

Trichothecenes are phytotoxic sesquiterpenic mycotoxins that can act as virulence factors in plant diseases. Harzianum A (HA) is a non-phytotoxic trichothecene produced by Trichoderma arundinaceum. The first step in HA biosynthesis is the conversion of farnesyl diphosphate to trichodiene (TD), a volatile organic compound (VOC), catalysed by a sesquiterpene synthase encoded by the tri5 gene.

Locomotor sensitization to ethanol impairs NMDA receptor-dependent synaptic plasticity in the nucleus accumbens and increases ethanol self-administration.

Although alcoholism is a worldwide problem resulting in millions of deaths, only a small percentage of alcohol users become addicted. The specific neural substrates responsible for individual differences in vulnerability to alcohol addiction are not known. In this study, we used rodent models to study behavioral and synaptic correlates related to individual differences in the development of ethanol locomotor sensitization, a form of drug-dependent behavioral plasticity associated with addiction vulnerability.

Relevance of trichothecenes in fungal physiology: disruption of tri5 in Trichoderma arundinaceum.

Trichothecenes are sesquiterpenoid mycotoxins produced mainly by Fusarium species. Harzianum A (HA), a non-phytotoxic trichothecene produced by Trichoderma arundinaceum, has recently been found to have antagonistic activity against fungal plant pathogens and to induce plant genes involved in defense responses. In the present work, we have shown that disruption of the T.

Thalamic glutamatergic afferents into the rat basolateral amygdala exhibit increased presynaptic glutamate function following withdrawal from chronic intermittent ethanol.

Amygdala glutamatergic neurotransmission regulates withdrawal induced anxiety-like behaviors following chronic ethanol exposure. The lateral/basolateral amygdala receives multiple glutamatergic projections that contribute to overall amygdala function. Our lab has previously shown that rat cortical (external capsule) afferents express postsynaptic alterations during chronic intermittent ethanol exposure and withdrawal.

Chronic intermittent ethanol and withdrawal differentially modulate basolateral amygdala AMPA-type glutamate receptor function and trafficking.

The amygdala plays a critical role in the generation and expression of anxiety-like behaviors including those expressed following withdrawal (WD) from chronic intermittent ethanol (CIE) exposure. In particular, the BLA glutamatergic system controls the expression of both innate and pathological anxiety. Recent data suggests that CIE and WD may functionally alter this system in a manner that closely parallels memory-related phenomena like long-term potentiation (LTP).

Trichothecenes: from simple to complex mycotoxins.

As the world's population grows, access to a safe food supply will continue to be a global priority. In recent years, the world has experienced an increase in mycotoxin contamination of grains due to climatic and agronomic changes that encourage fungal growth during cultivation. A number of the molds that are plant pathogens produce trichothecene mycotoxins, which are known to cause serious human and animal toxicoses.