Transcriptional analyses reveal different mechanism of toxicity for a chronic exposure to fluoxetine and venlafaxine on the brain of the marine fish Dicentrarchrus labrax

Abstract Polycystic ovary syndrome (PCOS) is the most common form of anovulatory infertility in women of reproductive age, characterised by androgen excess, polycystic appearance of the ovary and irregular menstruation. PCOS is also frequently associated with metabolic abnormalities, including increased adiposity and insulin resistance. The origins of PCOS are unknown, however recent findings in animal models strongly implicate androgen signalling in the brain in the development of PCOS pathophysiology. Exposure to androgen excess, either acutely during prenatal development or chronically from a peripubertal timepoint, can drive the development of PCOS-like features in adulthood. Prenatally androgenized (PNA) mice exhibit the cardinal reproductive features of PCOS and increased luteinizing hormone (LH) pulse frequency. This phenotype is associated with increased GABAergic innervation of gonadotropin-releasing hormone (GnRH) neurons, postulated to drive elevated GnRH/LH release and downstream effects. Chronic exposure to di-hydrotestosterone (DHT) from 3 weeks of age drives both reproductive and metabolic PCOS-like features that are ameliorated by selective AR loss from the brain. Here, we aimed to determine whether chronic exposure to DHT drives a similar increase in LH pulsatility and elevated GABAergic innervation to GnRH neurons as seen following prenatal exposure to androgen excess. GnRH-green fluorescent protein (GFP) female mice received either DHT or blank capsules for 90 days from postnatal day (PND) 21 (N = 6-7/group). Serial tail tip blood sampling was used to measure pulsatile LH and fixed brains were collected and immunolabelled for vesicular GABA transporter (VGAT) to assess putative GABAergic terminals associated with GFP-labelled GnRH neurons. Chronic androgen excess from the peripubertal period resulted in acyclicity and increased body weight as expected. However, LH pulsatility was not different between DHT-treated females and controls. Similarly, the density of VGAT appositions to GnRH neurons was not different between groups. Therefore, the programmed changes in the GnRH neuronal network and hyperactive LH secretion that result from prenatal androgen excess are not affected by chronic DHT exposure initiated at 3 weeks of age. These findings suggest that unique central mechanisms are involved in the reproductive impairments driven by exposure to androgen excess at different developmental stages.

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Studies on the Mechanism of Toxicity of DDT and Polychlorinated Biphenyls (PCBs): Disruption of Osmoregulation in Marine Fish

Environmental Health Perspectives ◽

10.2307/3428171 ◽

1972 ◽

Vol 1 ◽

pp. 169 ◽

Cited By ~ 1

Author(s):

W. B. Kinter ◽

L. S. Merkens ◽

R. H. Janicki ◽

A. M. Guarino

Keyword(s):

Polychlorinated Biphenyls ◽

Marine Fish ◽

Mechanism Of Toxicity

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A systematic review of neuroimaging and acute cannabis exposure in age-of-risk for psychosis

Translational Psychiatry ◽

10.1038/s41398-021-01295-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lani Cupo ◽

Eric Plitman ◽

Elisa Guma ◽

M. Mallar Chakravarty

Keyword(s):

Chronic Exposure ◽

Brain Regions ◽

Acute Exposure ◽

Psychotic Symptoms ◽

Long Term Effects ◽

Symptom Dimensions ◽

Increased Risk ◽

The Impact ◽

The Brain

AbstractAcute exposure to cannabis has been associated with an array of cognitive alterations, increased risk for neuropsychiatric illness, and other neuropsychiatric sequelae including the emergence of acute psychotic symptoms. However, the brain alterations associating cannabis use and these behavioral and clinical phenotypes remains disputed. To this end, neuroimaging can be a powerful technique to non-invasively study the impact of cannabis exposure on brain structure and function in both humans and animal models. While chronic exposure studies provide insight into how use may be related to long-term outcomes, acute exposure may reveal interesting information regarding the immediate impact of use and abuse on brain circuits. Understanding these alterations could reveal the connection with symptom dimensions in neuropsychiatric disorders and, more specifically with psychosis. The purpose of the present review is to: 1) provide an update on the findings of pharmacological neuroimaging studies examining the effects of administered cannabinoids and 2) focus the discussion on studies that examine the sensitive window for the emergence of psychosis. Current literature indicates that cannabis exposure has varied effects on the brain, with the principal compounds in cannabis (delta-9-tetrahydrocannabinol and cannabidiol) altering activity across different brain regions. Importantly, we also discovered critical gaps in the literature, particularly regarding sex-dependent responses and long-term effects of chronic exposure. Certain networks often characterized as dysregulated in psychosis, like the default mode network and limbic system, were also impacted by THC exposure, identifying areas of particular interest for future work investigating the potential relationship between the two.

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Morphochemical manifestations of chronic exposure of the brain to amphetamine and their correction by delta-sleep peptide

Bulletin of Experimental Biology and Medicine ◽

10.1007/bf00805174 ◽

1993 ◽

Vol 116 (5) ◽

pp. 1449-1451

Author(s):

L. M. Gershtein ◽

A. V. Sergutina ◽

V. I. Rakhmanova

Keyword(s):

Chronic Exposure ◽

Delta Sleep ◽

The Brain

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Chronic Exposure to Low Concentration Lead Chloride-Induced Anxiety and Loss of Aggression and Memory in Zebrafish

International Journal of Molecular Sciences ◽

10.3390/ijms21051844 ◽

2020 ◽

Vol 21 (5) ◽

pp. 1844 ◽

Cited By ~ 2

Author(s):

Ngoc Hieu Bui Thi ◽

Ngoc Anh Nguyen Thi ◽

Gilbert Audira ◽

Petrus Siregar ◽

Sung-Tzu Liang ◽

...

Keyword(s):

Chronic Exposure ◽

Predator Avoidance ◽

Short Term Memory ◽

Adult Zebrafish ◽

Short Term ◽

Term Memory ◽

Low Concentration ◽

Biochemical Assays ◽

The Brain

Lead and lead-derived compounds have been extensively utilized in industry, and their chronic toxicity towards aquatic animals has not been thoroughly addressed at a behavioral level. In this study, we assessed the risk of exposure to lead at a waterborne environmental concentration in adult zebrafish by behavioral and biochemical analyses. Nine tests, including three-dimension (3D) locomotion, novel tank exploration, mirror biting, predator avoidance, social interaction, shoaling, circadian rhythm locomotor activity, color preference, and a short-term memory test, were performed to assess the behavior of adult zebrafish after the exposure to 50 ppb PbCl2 for one month. The brain tissues were dissected and subjected to biochemical assays to measure the relative expression of stress biomarkers and neurotransmitters to elucidate the underlying mechanisms for behavioral alterations. The results of the behavioral tests showed that chronic exposure to lead could elevate the stress and anxiety levels characterized by elevated freezing and reduced exploratory behaviors. The chronic exposure to PbCl2 at a low concentration also induced a sharp reduction of aggressiveness and short-term memory. However, no significant change was found in predator avoidance, social interaction, shoaling, or color preference. The biochemical assays showed elevated cortisol and reduced serotonin and melatonin levels in the brain, thus, altering the behavior of the PbCl2-exposed zebrafish. In general, this study determined the potential ecotoxicity of long-term lead exposure in adult zebrafish through multiple behavioral assessments. The significant findings were that even at a low concentration, long-term exposure to lead could impair the memory and cause a decrease in the aggressiveness and exploratory activities of zebrafish, which may reduce their survival fitness.

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The effects of dietary selenomethionine on tissue-specific accumulation and toxicity of dietary arsenite in rainbow trout (Oncorhynchus mykiss) during chronic exposure

Metallomics ◽

10.1039/c8mt00309b ◽

2019 ◽

Vol 11 (3) ◽

pp. 643-655 ◽

Cited By ~ 5

Author(s):

Ankur Jamwal ◽

Yusuf Saibu ◽

Tracy C. MacDonald ◽

Graham N. George ◽

Som Niyogi

Keyword(s):

Rainbow Trout ◽

Oncorhynchus Mykiss ◽

Chronic Exposure ◽

Dietary Exposure ◽

Tissue Specific ◽

Rainbow Trout Oncorhynchus Mykiss ◽

Specific Accumulation ◽

The Brain

Selenomethionine facilitated arsenic deposition in the brain and likely in other tissues, possibly via bio-complexation. Elevated dietary selenomethionine can increase the tissue-specific accumulation and toxicity of As3+ in fish during chronic dietary exposure.

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