Neurotoxicology最新文献

{"title":"The association of manganese overexposure and neurobehavioral function is moderated by arsenic: A metal mixture analysis of children living near coal ash storage sites","authors":"Lonnie Sears ,&nbsp;Melissa J. Smith ,&nbsp;Lu Cai ,&nbsp;Kristina M. Zierold","doi":"10.1016/j.neuro.2024.06.005","DOIUrl":"https://doi.org/10.1016/j.neuro.2024.06.005","url":null,"abstract":"<div><p>Manganese is an essential element but can be neurotoxic if overexposed. Our previous study found that a higher level of manganese in nail biomarkers from children living near coal ash storage sites was associated with poorer neurobehavioral function. Children living near this type of pollution may be exposed to other metal neurotoxicants and a better understanding of manganese in the context of multiple exposures is needed. Mixture analyses were completed using nail samples from 251 children aged 6–14 years old. These biomarkers containing metals known to impact brain functioning were investigated to test our hypothesis that a mixture of metals including manganese impacts the development of children living near coal ash sites. Nails collected from children were analyzed using ICP-MS for manganese, arsenic, cadmium, lead, and zinc based on previous research on neurotoxicity. Bayesian kernel machine regression (BKMR) was used while adjusting for age, sex, and maternal education as potential covariates. Children also completed the Behavioral Assessment Research System (BARS) to provide neurobehavioral measures of attention and processing speed as outcomes for mixture analyses. Metal mixture analyses indicated that the relationship of manganese concentration and attention and processing speed was moderated by arsenic.,. When nail biomarkers for arsenic were highest (90th percentile), manganese was associated with poorer neurobehavioral performance on the BARS, measured by CPT hit latency. At low levels of arsenic (10th percentile), there was no evidence of harmful effects from overexposure to manganese on CPT hit latency based on BKMR analysis. Previously reported effects of manganese on neurobehavioral function may be moderated by arsenic exposure. Metal exposures and behavior outcomes can be studied with mixture analyses such as BKMR to evaluate effects of simultaneous exposures on children exposed to pollution.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"103 ","pages":"Pages 78-86"},"PeriodicalIF":3.4,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141313758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multigenerational effects of alcohol: A behavioral study in three zebrafish populations","authors":"Augusto Monteiro de Souza ,&nbsp;Maria Cecília Alves de Medeiros ,&nbsp;Jackson Nazareno Gomes-de-Lima ,&nbsp;Ana Carolina Luchiari","doi":"10.1016/j.neuro.2024.06.004","DOIUrl":"10.1016/j.neuro.2024.06.004","url":null,"abstract":"<div><p>Fetal alcohol exposure can result in fetal alcohol spectrum disorder (FASD), which encompasses a range of cognitive and behavioral impairments. Although zebrafish have been used as a reliable model to study FASD, little is known about the ontogeny of this disorder and population differences in subsequent generations not directly exposed to alcohol. In this study, we evaluated the behavioral outcomes of zebrafish populations AB, Outbred (OB), and Tubingen (TU), offspring of parents exposed to alcohol during embryonic development. The offspring of adult fish with FASD (exposed to 1 % alcohol at the embryonic stage) was compared to the offspring of unexposed parental fish (0 % alcohol at the embryo phase). The behavioral profile of the offspring was assessed at 6 days post-fertilization (dpf) and 45 dpf. At 6dpf, the AB FASD offspring exhibited hyperactivity and increased time at the edge of the tank, while the TU and OB FASD offspring showed hypoactivity. At 45dpf, TU fish maintained the larval locomotor pattern, characterized by decreased average speed and total distance traveled and increased immobility. However, AB and OB fish did not show alterations in locomotor activity and anxiety-related responses at 45dpf. Our results demonstrate, for the first time, that FASD zebrafish offspring display behavioral differences, which were most evident during the early ontogenetic phase (6dpf) but may vary throughout animal ontogeny. TU fish exhibited the most consistent behavioral pattern across different developmental stages. These findings provide insights into the multigenerational and persistent behavioral consequences of embryonic alcohol exposure in zebrafish. Further research should focus on other features that can be inherited and the development of treatments for the offspring affected by it.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"103 ","pages":"Pages 115-122"},"PeriodicalIF":3.4,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurotoxicology of dopamine: Victim or assailant?","authors":"Meghan L. Bucher ,&nbsp;Jocelyn Dicent ,&nbsp;Carolina Duarte Hospital ,&nbsp;Gary W. Miller","doi":"10.1016/j.neuro.2024.06.001","DOIUrl":"10.1016/j.neuro.2024.06.001","url":null,"abstract":"<div><p>Since the identification of dopamine as a neurotransmitter in the mid-20th century, investigators have examined the regulation of dopamine homeostasis at a basic biological level and in human disorders. Genetic animal models that manipulate the expression of proteins involved in dopamine homeostasis have provided key insight into the consequences of dysregulated dopamine. As a result, we have come to understand the potential of dopamine to act as an endogenous neurotoxin through the generation of reactive oxygen species and reactive metabolites that can damage cellular macromolecules. Endogenous factors, such as genetic variation and subcellular processes, and exogenous factors, such as environmental exposures, have been identified as contributors to the dysregulation of dopamine homeostasis. Given the variety of dysregulating factors that impact dopamine homeostasis and the potential for dopamine itself to contribute to further cellular dysfunction, dopamine can be viewed as both the victim and an assailant of neurotoxicity<strong>.</strong> Parkinson’s disease has emerged as the exemplar case study of dopamine dysregulation due to the genetic and environmental factors known to contribute to disease risk, and due to the evidence of dysregulated dopamine as a pathologic and pathogenic feature of the disease. This review, inspired by the talk, “Dopamine in Durham: location, location, location” presented by Dr. Miller for the Jacob Hooisma Memorial Lecture at the International Neurotoxicology Association meeting in 2023, offers a primer on dopamine toxicity covering endogenous and exogenous factors that disrupt dopamine homeostasis and the actions of dopamine as an endogenous neurotoxin.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"103 ","pages":"Pages 175-188"},"PeriodicalIF":3.4,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglial Sp1 induced LRRK2 upregulation in response to manganese exposure, and 17β-estradiol afforded protection against this manganese toxicity","authors":"Ivan Nyarko-Danquah ,&nbsp;Edward Pajarillo ,&nbsp;Sanghoon Kim ,&nbsp;Alexis Digman ,&nbsp;Harpreet Kaur Multani ,&nbsp;Itunu Ajayi ,&nbsp;Deok-Soo Son ,&nbsp;Michael Aschner ,&nbsp;Eunsook Lee","doi":"10.1016/j.neuro.2024.05.007","DOIUrl":"10.1016/j.neuro.2024.05.007","url":null,"abstract":"<div><p>Chronic exposure to elevated levels of manganese (Mn) causes a neurological disorder referred to as manganism, presenting symptoms similar to those of Parkinson’s disease (PD), yet the mechanisms by which Mn induces its neurotoxicity are not completely understood. 17β-estradiol (E2) affords neuroprotection against Mn toxicity in various neural cell types including microglia. Our previous studies have shown that leucine-rich repeat kinase 2 (LRRK2) mediates Mn-induced inflammatory toxicity in microglia. The LRRK2 promoter sequences contain three putative binding sites of the transcription factor (TF), specificity protein 1 (Sp1), which increases LRRK2 promoter activity. In the present study, we tested if the Sp1-LRRK2 pathway plays a role in both Mn toxicity and the protection afforded by E2 against Mn toxicity in BV2 microglial cells. The results showed that Mn induced cytotoxicity, oxidative stress, and tumor necrosis factor-α production, which were attenuated by an LRRK2 inhibitor, GSK2578215A. The overexpression of Sp1 increased LRRK2 promoter activity, mRNA and protein levels, while inhibition of Sp1 with its pharmacological inhibitor, mithramycin A, attenuated the Mn-induced increases in LRRK2 expression. Furthermore, E2 attenuated the Mn-induced Sp1 expression by decreasing the expression of Sp1 via the promotion of the ubiquitin-dependent degradation pathway, which was accompanied by increased protein levels of RING finger protein 4, the E3-ligase of Sp1, Sp1 ubiquitination, and SUMOylation. Taken together, our novel findings suggest that Sp1 serves as a critical TF in Mn-induced LRRK2 expression as well as in the protection afforded by E2 against Mn toxicity through reduction of LRRK2 expression in microglia.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"103 ","pages":"Pages 105-114"},"PeriodicalIF":3.4,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A zebrafish-based acoustic motor response (AMR) assay to evaluate chemical-induced developmental neurotoxicity","authors":"Demetrius McAtee,&nbsp;Ahmed Abdelmoneim","doi":"10.1016/j.neuro.2024.06.003","DOIUrl":"10.1016/j.neuro.2024.06.003","url":null,"abstract":"<div><p>Behavioral assays using early-developing zebrafish (<em>Danio rerio</em>) offer a valuable supplement to the <em>in vitro</em> battery adopted as new approach methodologies (NAMs) for assessing risk of chemical-induced developmental neurotoxicity. However, the behavioral assays primarily adopted rely on visual stimulation to elicit behavioral responses, known as visual motor response (VMR) assays. Ocular deficits resulting from chemical exposures can, therefore, confound the behavioral responses, independent of effects on the nervous system. This highlights the need for complementary assays employing alternative forms of sensory stimulation. In this study, we investigated the efficacy of acoustic stimuli as triggers of behavioral responses in larval zebrafish, determined the most appropriate data acquisition mode, and evaluated the suitability of an acoustic motor response (AMR) assay as means to assess alterations in brain activity and risk of chemical-induced developmental neurotoxicity. We quantified the motor responses of 120 h post-fertilization (hpf) larvae to acoustic stimuli with varying patterns and frequencies, and determined the optimal time intervals for data acquisition. Following this, we examined changes in acoustic and visual motor responses resulting from exposures to pharmacological agents known to impact brain activity (pentylenetetrazole (PTZ) and tricaine-s (MS-222)). Additionally, we examined the AMR and VMR of larvae following exposure to two environmental contaminants associated with developmental neurotoxicity: arsenic (As) and cadmium (Cd). Our findings indicate that exposure to a 100 Hz sound frequency in 100 ms pulses elicits the strongest behavioral response among the acoustic stimuli tested and data acquisition in 2 s time intervals is suitable for response assessment. Exposure to PTZ exaggerated and depressed both AMR and VMR in a concentration-dependent manner, while exposure to MS-222 only depressed them. Similarly, exposure to As and Cd induced respective hyper- and hypo-activation of both motor responses. This study highlights the efficiency of the proposed zebrafish-based AMR assay in demonstrating risk of chemical-induced developmental neurotoxicity and its suitability as a complement to the widely adopted VMR assay.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"103 ","pages":"Pages 60-70"},"PeriodicalIF":3.4,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fruit ripening retardant Daminozide induces cognitive impairment, cell specific neurotoxicity, and genotoxicity in Drosophila melanogaster","authors":"Debasmita Das ,&nbsp;Gaurab Ghosh ,&nbsp;Arthita Dutta ,&nbsp;Rinchen D. Sherpa ,&nbsp;Papiya Ghosh ,&nbsp;Subhra Prakash Hui ,&nbsp;Sujay Ghosh","doi":"10.1016/j.neuro.2024.06.002","DOIUrl":"10.1016/j.neuro.2024.06.002","url":null,"abstract":"<div><h3>Background</h3><p>We explored neurotoxic and genotoxic effects of Daminozide, a fruit ripening retardant, on the brain of <em>Drosophila melanogaster</em>, based on our previous finding of DNA fragmentation in larval brain cell in the flies experimentally exposed to this chemicals.</p></div><div><h3>Methods</h3><p>Adult flies were subjected to two distinct concentrations of daminozide (200 mg/L and 400 mg/L) mixed in culture medium, followed by an examination of specific behaviors such as courtship conditioning and aversive phototaxis, which serve as indicators of cognitive functions. We investigated brain histology and histochemistry to assess the overall toxicity of daminozide, focusing on neuron type-specific effects. Additionally, we conducted studies on gene expression specific to neuronal function. Statistical comparisons were then made between the exposed and control flies across all tested attributes.</p></div><div><h3>Results</h3><p>The outcome of behavioral assays suggested deleterious effects of Daminozide on learning, short term and long term memory function. Histological examination of brain sections revealed cellular degeneration, within Kenyon cell neuropiles in Daminozide-exposed flies. Neurone specific Immuno-histochemistry study revealed significant reduction of dopaminergic and glutaminergic neurones with discernible reduction in cellular counts, alteration in cell and nuclear morphology among daminozide exposed flies. Gene expression analyses demonstrated upregulation of <em>rutabaga (rut)</em>, <em>hb9</em> and down regulation of <em>PKa- C1</em>, <em>CrebB</em>, <em>Ace</em> and <em>nAchRbeta</em>-1 in exposed flies which suggest dysregulation of gene functions involved in motor neuron activity, learning, and memory.</p></div><div><h3>Conclusion</h3><p>Taken together, our findings suggests that Daminozide induces multifaceted harmful impacts on the neural terrain of <em>Drosophila melanogaster</em>, posing a threat to its cognitive abilities.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"103 ","pages":"Pages 123-133"},"PeriodicalIF":3.4,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of N-acetylcysteine on the neurotoxicity of sevoflurane in developing hippocampus cells","authors":"Esra Adiyeke ,&nbsp;Nurten Bakan ,&nbsp;Ayca Uvez ,&nbsp;Devrim OZ Arslan ,&nbsp;Sima Kilic ,&nbsp;Berkcan Koc ,&nbsp;Samed Ozer ,&nbsp;Ozlem Saatci ,&nbsp;Elif İlkay Armutak","doi":"10.1016/j.neuro.2024.05.006","DOIUrl":"10.1016/j.neuro.2024.05.006","url":null,"abstract":"<div><p>Sevoflurane, a common pediatric anesthetic, has been linked to neurodegeneration, raising safety concerns. This study explored N-acetylcysteine's protective potential against sevoflurane-induced neurotoxicity in rat hippocampi. Four groups were examined: Control: Received 6 hours of 3 l/min gas (air and 30 % O2) and intraperitoneal saline. NAC: Received 6 hours of 3 l/min gas and 150 mg/kg NAC intraperitoneally. Sev: Exposed to 6 hours of 3 l/min gas and 3 % sevoflurane. Sev+NAC: Received 6 hours of 3 l/min gas, 3 % sevoflurane, and 150 mg/kg NAC. Protein levels of NRF-2, NLRP3, IL-1β, caspase-1, Beclin 1, p62, LC3A, and apoptosis markers were assessed. Sevoflurane and NAC alone reduced autophagy, while Sev+NAC group maintained autophagy levels. Sev group had elevated NRF-2, NLRP3, pNRF2, Caspase-1, and IL-1β, which were reduced in Sev+NAC. Apoptosis was higher in Sev, but Sev+NAC showed reduced apoptosis compared to the control. In summary, sevoflurane induced neurotoxicity in developing hippocampus, which was mitigated by N-acetylcysteine administration.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"103 ","pages":"Pages 96-104"},"PeriodicalIF":3.4,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) induces depression-like phenotype","authors":"Roanna A. Debler ,&nbsp;Paula L. Gallegos ,&nbsp;Alexandra C. Ojeda ,&nbsp;Andrea M. Perttula ,&nbsp;Ashley Lucio ,&nbsp;Robert S. Chapkin ,&nbsp;Stephen Safe ,&nbsp;Shoshana Eitan","doi":"10.1016/j.neuro.2024.05.010","DOIUrl":"10.1016/j.neuro.2024.05.010","url":null,"abstract":"<div><p>The etiology of major depressive disorder (MDD) remains poorly understood. Our previous studies suggest a role for the aryl hydrocarbon receptor (AhR) in depression. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a toxic environmental contaminant, with a high AhR binding affinity, and an established benchmark for assessing AhR activity. Therefore, this study examined the effect of TCDD on depression-like behaviors. Female mice were fed standard chow or a high-fat diet (HFD) for 11 weeks, and their weight was recorded. Subsequently, they were tested for baseline sucrose preference and splash test grooming. Then, TCDD (0.1<!--> <!-->µg/kg/day) or vehicle was administered orally for 28 days, and mice were examined for their sucrose preference and performances in the splash test, forced swim test (FST), and Morris water maze (MWM) task. TCDD significantly decreased sucrose preference, increased FST immobility time, and decreased groom time in chow-fed mice. HFD itself significantly reduced sucrose preference. However, TCDD significantly increased FST immobility time and decreased groom time in HFD-fed mice. A small decrease in bodyweight was observed only at the fourth week of daily TCDD administration in chow-fed mice, and no significant effects of TCDD on bodyweights were observed in HFD-fed mice. TCDD did not have a significant effect on spatial learning in the MWM. Thus, this study demonstrated that TCDD induces a depression-like state, and the effects were not due to gross lethal toxicity. This study further suggests that more studies should examine a possible role for AhR and AhR-active environmental pollutants in precipitating or worsening MDD.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"103 ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delineating the molecular mechanisms of hippocampal neurotoxicity induced by chronic administration of synthetic cannabinoid AB-FUBINACA in mice","authors":"Ayman Alzu'bi ,&nbsp;Ejlal Abu-El-Rub ,&nbsp;Fatimah Almahasneh ,&nbsp;Lena Tahat ,&nbsp;Rabaa Y. Athamneh ,&nbsp;Ramada Khasawneh ,&nbsp;Hiba Alzoubi ,&nbsp;Doaa S. Ghorab ,&nbsp;Rawan Almazari ,&nbsp;Mazhar Salim Al Zoubi ,&nbsp;Raed M. Al-Zoubi","doi":"10.1016/j.neuro.2024.05.009","DOIUrl":"10.1016/j.neuro.2024.05.009","url":null,"abstract":"<div><p>Chronic use of synthetic cannabinoids (SCs) has been associated with cognitive and behavioural deficits and an increased risk of neuropsychiatric disorders. The underlying molecular and cellular mechanisms of the neurotoxic effects of long-term use of SCs have not been well investigated in the literature. Herein, we evaluated the in vivo effects of chronic administration of AB-FUBINACA on the hippocampus in mice. Our results revealed that the administration of AB-FUBINACA induced a significant impairment in recognition memory associated with histopathological changes in the hippocampus. These findings were found to be correlated with increased level of oxidative stress, neuroinflammation, and apoptosis markers, and reduced expression of brain-derived neurotrophic factor (BDNF), which plays an essential role in modulating synaptic plasticity integral for promoting learning and memory in the hippocampus. Additionally, we showed that AB-FUBINACA significantly decreased the expression of NR1, an important functional subunit of glutamate/NMDA receptors and closely implicated in the development of toxic psychosis. These findings shed light on the long-term neurotoxic effects of SCs on hippocampus and the underlying mechanisms of these effects. This study provided new targets for possible medical interventions to improve the treatment guidelines for SCs addiction.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"103 ","pages":"Pages 50-59"},"PeriodicalIF":3.4,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0161813X24000548/pdfft?md5=8b542e5ce336b9e3609dbfdb42db99d2&pid=1-s2.0-S0161813X24000548-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persisting neurobehavioral consequences of daily or intermittent paternal cannabis administration in F1 and F2 Rats","authors":"Andrew B. Hawkey ,&nbsp;Sarabesh Natarajan ,&nbsp;Olivia Kelly ,&nbsp;Anas Gondal ,&nbsp;Corinne Wells ,&nbsp;Michelle Louise Jones ,&nbsp;Amir H. Rezvani ,&nbsp;Susan K. Murphy ,&nbsp;Edward D. Levin","doi":"10.1016/j.neuro.2024.05.005","DOIUrl":"10.1016/j.neuro.2024.05.005","url":null,"abstract":"<div><p>Repeated paternal preconception exposure to Δ⁹-tetrahydrocannabinol (Δ⁹-THC) alone or together with the other constituents in a cannabis extract has been shown in our earlier studies in rats to cause significant neurobehavioral impairment in their offspring. In the current study, we compared the effects of daily cannabis extract (CE) exposure to cannabis on two consecutive days per week, modeling weekend cannabis use in human. The CE contained Δ⁹-THC as well as cannabidiol and cannabinol. We also extended the investigation of the study to cross-generational effects of grand-paternal cannabis exposure on the F2 generation and included testing the effects of paternal cannabis exposure on responding for opiate self-administration in F1 and F2 generation offspring. We replicated the findings of neurobehavioral impairment in F1 offspring of male rats exposed to cannabis extract containing 4 mg/kg/day of Δ⁹-THC daily for four weeks prior to mating with drug naïve females. The 4-week cannabis extract exposure caused a significant decrease in weight gain in the male rats exposed daily. In contrast, their offspring showed significantly greater body weights and anogenital distances (AGD) in the third to fourth weeks after birth. The behavioral effects seen in the F1 generation were increased habituation of locomotor activity in the figure-8 maze in female offspring and increased lever pressing for the opiate drug remifentanil in male offspring. The F2 generation showed significantly impaired negative geotaxis and an elimination of the typical sex-difference in locomotor activity, with effects not seen in the F1 generation. This study shows that daily paternal cannabis exposure for four weeks prior to mating causes significant neurobehavioral impairment in the F1 and F2 offspring. Intermittent exposure on two consecutive days per week for four weeks caused comparable neurobehavioral impairment. In sum, there should be concern about paternal as well as maternal exposure to cannabis concerning neurobehavioral development of their offspring.</p></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"103 ","pages":"Pages 27-38"},"PeriodicalIF":3.4,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141175518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}