Maternal Exposure to Di-(2-ethylhexyl) Phthalate Impairs Hippocampal Synaptic Plasticity in Male Offspring: Involvement of Damage to Dendritic Spine Development.

Abstract:

:Exposure to di-(2-ethylhexyl) phthalate (DEHP), a widely used kind of plasticizer, can result in neurodevelopment impairments and learning and memory disorders. We studied the effects and possible mechanisms of maternal DEHP treatment on hippocampal synaptic plasticity in offspring. Pregnant Wistar rats were randomly divided into four groups and received 0, 30, 300, 750 (mg/kg)/d DEHP by gavage from gestational day (GD) 0 to postnatal day (PN) 21. Our data showed that DEHP exposure impaired hippocampal synaptic plasticity, damaged synaptic ultrastructure, and decreased synaptic protein levels in male pups. Furthermore, DEHP decreased the density of dendritic spines, affected F-actin polymerization, and downregulated the Rac1/PAK/LIMK1/cofilin signaling pathway in male offspring. However, the alterations in the hippocampi of female offspring were not observed. These results illustrate that maternal DEHP exposure could impair hippocampal synaptic plasticity by affecting synaptic structure and dendritic spine development in male offspring, which may be attributed to altered cytoskeleton construction induced by downregulation of the Rac1/PAK/LIMK1/cofilin signaling pathway.

journal_name

ACS Chem Neurosci

authors

Dong J,Fu H,Fu Y,You M,Li X,Wang C,Leng K,Wang Y,Chen J

doi

10.1021/acschemneuro.0c00612

subject

Has Abstract

pub_date

2021-01-20 00:00:00

pages

311-322

issue

2

issn

1948-7193

journal_volume

12

pub_type

杂志文章
  • The KDM5 Inhibitor KDM5-C70 Induces Astrocyte Differentiation in Rat Neural Stem Cells.

    abstract::Members of the lysine-specific histone demethylase 5 (KDM5/JARID1) family are known to play important roles in stem cell fate determination. Here, using the KDM5 inhibitor C70 (KDM5-C70), we demonstrated that the histone demethylase activity of the KDM5 enzyme is essential for the repression of astrocytic differentiat...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.0c00613

    authors: Lee HR,Ann J,Kim YM,Lee J,Kim HJ

    更新日期:2021-01-22 00:00:00

  • Recent Advances in Virtual Screening for Cholinesterase Inhibitors.

    abstract::Alzheimer's disease (AD) is a significant health crisis, and current treatments provide only limited benefits to cognition at the cost of serious side effects. Recently, virtual screening techniques such as ligand-based virtual screening (LBVS) and structure-based virtual screening (SBVS) have emerged as powerful drug...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.0c00627

    authors: Miles JA,Ross BP

    更新日期:2021-01-06 00:00:00

  • Omarigliptin Mitigates Lipopolysaccharide-Induced Neuroinflammation and Dysfunction of the Integrity of the Blood-Brain Barrier.

    abstract::The blood-brain barrier (BBB) is an important barrier that separates brain tissue from peripheral blood. The permeability of the BBB can be destroyed by external harmful factors, such as lipopolysaccharide (LPS), which contributes to neuroinflammation and central nervous system diseases. The present study aims to inve...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.0c00537

    authors: Du H,Wang S

    更新日期:2020-12-16 00:00:00

  • Serotonergic Approaches in Parkinson's Disease: Translational Perspectives, an Update.

    abstract::Parkinson's disease (PD) has long been seen as a disorder caused by degeneration of the dopaminergic system, leading to the classic motor manifestations of the disease. However, there is now overwhelming evidence that PD is more than a disease merely caused by dopamine depletion. It is well-known that a myriad of othe...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章,评审

    doi:10.1021/acschemneuro.6b00440

    authors: Huot P,Sgambato-Faure V,Fox SH,McCreary AC

    更新日期:2017-05-17 00:00:00

  • Ethylatropine Bromide as a Peripherally Restricted Muscarinic Antagonist.

    abstract::Quaternary ammonium analogues of atropine that are unable to cross the blood-brain barrier are used to alleviate peripheral muscarinic toxicity in animal models of epilepsy produced by systemic administration of pilocarpine or diisopropylfluorophosphate (DFP). Currently, methylatropine is the most popular and potent o...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.6b00334

    authors: Rojas A,Ganesh T,Walker A,Dingledine R

    更新日期:2017-04-19 00:00:00

  • An early folding contact between Phe19 and Leu34 is critical for amyloid-β oligomer toxicity.

    abstract::Small hydrophobic oligomers of aggregation-prone proteins are thought to be generically toxic. Here we examine this view by perturbing an early folding contact between Phe19 and Leu34 formed during the aggregation of Alzheimer's amyloid-β (Aβ40) peptide. We find that even conservative single mutations altering this in...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.5b00074

    authors: Das AK,Rawat A,Bhowmik D,Pandit R,Huster D,Maiti S

    更新日期:2015-08-19 00:00:00

  • Phospho-Tau Impairs Nuclear-Cytoplasmic Transport.

    abstract::Aggregation of hyperphosphorylated tau is the hallmark of several tauopathies, including Alzheimer's disease (AD). Although the mechanism underlying tau-associated neuronal damage remains unclear, it is believed that tau hyperphosphorylation is one of the key features in disease progression. A recent study demonstrate...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章,评审

    doi:10.1021/acschemneuro.8b00632

    authors: Tripathi T,Prakash J,Shav-Tal Y

    更新日期:2019-01-16 00:00:00

  • Microglia-Based Phenotypic Screening Identifies a Novel Inhibitor of Neuroinflammation Effective in Alzheimer's Disease Models.

    abstract::Currently, anti-AD drug discovery using target-based approaches is extremely challenging due to unclear etiology of AD and absence of validated therapeutic protein targets. Neuronal death, regardless of causes, plays a key role in AD progression, and it is directly linked to neuroinflammation. Meanwhile, phenotypic sc...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.6b00125

    authors: Zhou W,Zhong G,Fu S,Xie H,Chi T,Li L,Rao X,Zeng S,Xu D,Wang H,Sheng G,Ji X,Liu X,Ji X,Wu D,Zou L,Tortorella M,Zhang K,Hu W

    更新日期:2016-11-16 00:00:00

  • Discovery of Small Molecule Kappa Opioid Receptor Agonist and Antagonist Chemotypes through a HTS and Hit Refinement Strategy.

    abstract::Herein we present the outcome of a high throughput screening (HTS) campaign-based strategy for the rapid identification and optimization of selective and general chemotypes for both kappa (κ) opioid receptor (KOR) activation and inhibition. In this program, we have developed potent antagonists (IC(50) < 120 nM) or ago...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/cn200128x

    authors: Frankowski KJ,Hedrick MP,Gosalia P,Li K,Shi S,Whipple D,Ghosh P,Prisinzano TE,Schoenen FJ,Su Y,Vasile S,Sergienko E,Gray W,Hariharan S,Milan L,Heynen-Genel S,Mangravita-Novo A,Vicchiarelli M,Smith LH,Streicher JM,

    更新日期:2012-03-21 00:00:00

  • Identification of Metabotropic Glutamate Receptor Subtype 5 Potentiators Using Virtual High-Throughput Screening.

    abstract::Selective potentiators of glutamate response at metabotropic glutamate receptor subtype 5 (mGluR5) have exciting potential for the development of novel treatment strategies for schizophrenia. A total of 1,382 compounds with positive allosteric modulation (PAM) of the mGluR5 glutamate response were identified through h...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/cn9000389

    authors: Mueller R,Rodriguez AL,Dawson ES,Butkiewicz M,Nguyen TT,Oleszkiewicz S,Bleckmann A,Weaver CD,Lindsley CW,Conn PJ,Meiler J

    更新日期:2010-04-21 00:00:00

  • Ethanol Induced Brain Lipid Changes in Mice Assessed by Mass Spectrometry.

    abstract::Alcohol abuse is a chronic disease characterized by the consumption of alcohol at a level that interferes with physical and mental health and causes serious and persistent changes in the brain. Lipid metabolism is of particular interest due to its high concentration in the brain. Lipids are the main component of cell ...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.6b00120

    authors: Roux A,Jackson SN,Muller L,Barbacci D,O'Rourke J,Thanos PK,Volkow ND,Balaban C,Schultz JA,Woods AS

    更新日期:2016-08-17 00:00:00

  • Misfolded SOD1 Accumulation and Mitochondrial Association Contribute to the Selective Vulnerability of Motor Neurons in Familial ALS: Correlation to Human Disease.

    abstract::Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder, with a 10% genetic linkage, of which 20% of these cases may be attributed to mutations in superoxide dismutase (SOD1). Specific mutations in SOD1 have been associated with disease duration, which can be highly variable ranging from a life...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.7b00140

    authors: Abu-Hamad S,Kahn J,Leyton-Jaimes MF,Rosenblatt J,Israelson A

    更新日期:2017-10-18 00:00:00

  • D-512 and D-440 as novel multifunctional dopamine agonists: characterization of neuroprotection properties and evaluation of in vivo efficacy in a Parkinson's disease animal model.

    abstract::In this article, we have demonstrated the in vivo efficacy of D-512 and D-440 in a 6-OHDA-induced unilaterally lesioned rat model experiment, a Parkinson's disease animal model. D-512 is a novel highly potent D2/D3 agonist, and D-440 is a novel highly selective D3 agonist. We evaluated the neuroprotective properties o...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/cn400106n

    authors: Santra S,Xu L,Shah M,Johnson M,Dutta A

    更新日期:2013-10-16 00:00:00

  • Benzothiophene Selective Estrogen Receptor Modulators Provide Neuroprotection by a novel GPR30-dependent Mechanism.

    abstract::The clinical benzothiophene SERM (BT-SERM), raloxifene, was compared with estrogens in protection of primary rat neurons against oxygen-glucose deprivation (OGD). Structure-activity relationships for neuroprotection were determined for a family of BT-SERMs displaying a spectrum of ERα and ERβ binding affinity and agon...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/cn100106a

    authors: Abdelhamid R,Luo J,Vandevrede L,Kundu I,Michalsen B,Litosh VA,Schiefer IT,Gherezghiher T,Yao P,Qin Z,Thatcher GR

    更新日期:2011-05-18 00:00:00

  • Interrogating the Molecular Basis for Substrate Recognition in Serotonin and Dopamine Transporters with High-Affinity Substrate-Based Bivalent Ligands.

    abstract::The transporters for the neurotransmitters serotonin and dopamine (SERT and DAT, respectively) are targets for drugs used in the treatment of mental disorders and widely used drugs of abuse. Studies of prokaryotic homologues have advanced our structural understanding of SERT and DAT, but it still remains enigmatic whe...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.6b00164

    authors: Andersen J,Ladefoged LK,Kristensen TN,Munro L,Grouleff J,Stuhr-Hansen N,Kristensen AS,Schiøtt B,Strømgaard K

    更新日期:2016-10-19 00:00:00

  • Assessment of tissue viability following electroosmotic push-pull perfusion from organotypic hippocampal slice cultures.

    abstract::We have developed a novel sampling technique that allows both introduction and removal of fluid from the extracellular space of living tissue. This method is based on the fluidics of push-pull perfusion but flow is driven by electroosmosis. We have applied this method to organotypic hippocampal cultures. A source capi...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/cn4000814

    authors: Rupert AE,Ou Y,Sandberg M,Weber SG

    更新日期:2013-05-15 00:00:00

  • Comparison of the binding and functional properties of two structurally different D2 dopamine receptor subtype selective compounds.

    abstract::We previously reported on the synthesis of substituted phenyl-4-hydroxy-1-piperidyl indole analogues with nanomolar affinity at D2 dopamine receptors, ranging from 10- to 100-fold selective for D2 compared to the D3 dopamine receptor subtype. More recently, we evaluated a panel of aripiprazole analogues, identifying s...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/cn300142q

    authors: Luedtke RR,Mishra Y,Wang Q,Griffin SA,Bell-Horner C,Taylor M,Vangveravong S,Dillon GH,Huang RQ,Reichert DE,Mach RH

    更新日期:2012-12-19 00:00:00

  • DARK Classics in Chemical Neuroscience: Morphine.

    abstract::As the major psychoactive agent in opium and direct precursor for heroin, morphine is a historically critical molecule in chemical neuroscience. A structurally complex phenanthrene alkaloid produced by Papaver somniferum, morphine has fascinated chemists seeking to disentangle pharmacologically beneficial analgesic ef...

    journal_title:ACS chemical neuroscience

    pub_type: 历史文章,杂志文章,评审

    doi:10.1021/acschemneuro.8b00150

    authors: Devereaux AL,Mercer SL,Cunningham CW

    更新日期:2018-10-17 00:00:00

  • Neurotensin Analogues Containing Cyclic Surrogates of Tyrosine at Position 11 Improve NTS2 Selectivity Leading to Analgesia without Hypotension and Hypothermia.

    abstract::Neurotensin (NT) exerts its analgesic effects through activation of the G protein-coupled receptors NTS1 and NTS2. This opioid-independent antinociception represents a potential alternative for pain management. While activation of NTS1 also induces a drop in blood pressure and body temperature, NTS2 appears to be an a...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.9b00390

    authors: Eiselt E,Gonzalez S,Martin C,Chartier M,Betti C,Longpré JM,Cavelier F,Tourwé D,Gendron L,Ballet S,Sarret P

    更新日期:2019-11-20 00:00:00

  • A small linear peptide encompassing the NGF N-terminus partly mimics the biological activities of the entire neurotrophin in PC12 cells.

    abstract::Ever since the discovery of its neurite growth promoting activity in sympathetic and sensory ganglia, nerve growth factor (NGF) became the prototype of the large family of neurotrophins. The use of primary cultures and clonal cell lines has revealed several distinct actions of NGF and other neurotrophins. Among severa...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.5b00069

    authors: Travaglia A,Pietropaolo A,Di Martino R,Nicoletti VG,La Mendola D,Calissano P,Rizzarelli E

    更新日期:2015-08-19 00:00:00

  • DARK Classics in Chemical Neuroscience: Aminorex Analogues.

    abstract::Aminorex (5-phenyl-4,5-dihydro-1,3-oxazol-2-amine) and 4-methylaminorex (4-methyl-5-phenyl-4,5-dihydro-1,3-oxazol-2-amine) are psychostimulants that have long been listed in Schedules IV and I of the UN Convention on Psychotropic Substances of 1971. However, a range of psychoactive analogues exist that are not interna...

    journal_title:ACS chemical neuroscience

    pub_type: 历史文章,杂志文章,评审

    doi:10.1021/acschemneuro.8b00415

    authors: Maier J,Mayer FP,Brandt SD,Sitte HH

    更新日期:2018-10-17 00:00:00

  • Histamine H3 receptor activation counteracts adenosine A2A receptor-mediated enhancement of depolarization-evoked [3H]-GABA release from rat globus pallidus synaptosomes.

    abstract::High levels of histamine H3 receptors (H3Rs) are found in the globus pallidus (GP), a neuronal nucleus in the basal ganglia involved in the control of motor behavior. By using rat GP isolated nerve terminals (synaptosomes), we studied whether H3R activation modified the previously reported enhancing action of adenosin...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/cn500001m

    authors: Morales-Figueroa GE,Márquez-Gómez R,González-Pantoja R,Escamilla-Sánchez J,Arias-Montaño JA

    更新日期:2014-08-20 00:00:00

  • Future Priorities in Tackling Infections Due to Brain-Eating Amoebae.

    abstract::Brain-eating amoebae (Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria fowleri) can cause opportunistic infections involving the central nervous system. It is troubling that the mortality rate is more than 90% despite advances in antimicrobial chemotherapy over the last few decades. Here, we describe urgent k...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.7b00343

    authors: Khan NA,Anwar A,Siddiqui R

    更新日期:2017-11-15 00:00:00

  • Synaptic plasticity, a symphony in GEF.

    abstract::Dendritic spines are the postsynaptic sites for the majority of excitatory synapses in the mammalian forebrain. While many spines display great stability, others change shape in a matter of seconds to minutes. These rapid alterations in dendritic spine number and size require tight control of the actin cytoskeleton, t...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/cn100012x

    authors: Kiraly DD,Eipper-Mains JE,Mains RE,Eipper BA

    更新日期:2010-05-19 00:00:00

  • Structural Modeling of γ-Secretase Aβ n Complex Formation and Substrate Processing.

    abstract::The intramembrane aspartyl protease γ-secretase (GSEC) cleaves single-span transmembrane helices including the C-terminal fragment of the amyloid precursor protein (APP). This substrate is initially cleaved at the ϵ-site followed by successive processing (trimming) events mostly in steps of three amino acids. GSEC is ...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.8b00725

    authors: Hitzenberger M,Zacharias M

    更新日期:2019-03-20 00:00:00

  • Serotonin: A New Hope in Alzheimer's Disease?

    abstract::Alzheimer's disease (AD) is the most common form of dementia affecting 35 million individuals worldwide. Current AD treatments provide only brief symptomatic relief. It is therefore urgent to replace this symptomatic approach with a curative one. Increasing serotonin signaling as well as developing molecules that enha...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.5b00135

    authors: Claeysen S,Bockaert J,Giannoni P

    更新日期:2015-07-15 00:00:00

  • Targeting Chondroitin Sulfate Proteoglycans: An Emerging Therapeutic Strategy to Treat CNS Injury.

    abstract::Chondroitin sulfate proteoglycans (CSPGs) are the most abundant components of glial scar formed after severe traumatic brain injury as well as spinal cord injury and play a crucial inhibitory role in axonal regeneration by selective contraction of filopodia of the growth cone of sprouting neurites. Healing of central ...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.0c00004

    authors: Mukherjee N,Nandi S,Garg S,Ghosh S,Ghosh S,Samat R,Ghosh S

    更新日期:2020-02-05 00:00:00

  • N-Terminal Acetylation Preserves α-Synuclein from Oligomerization by Blocking Intermolecular Hydrogen Bonds.

    abstract::The abnormal aggregation of α-synuclein (α-Syn) is closely associated with Parkinson's disease. Different post-translational modifications of α-Syn have been identified and contribute distinctly in α-Syn aggregation and cytotoxicity. Recently, α-Syn was reported to be N-terminally acetylated in cells, yet the function...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.7b00250

    authors: Bu B,Tong X,Li D,Hu Y,He W,Zhao C,Hu R,Li X,Shao Y,Liu C,Zhao Q,Ji B,Diao J

    更新日期:2017-10-18 00:00:00

  • Promotion of Neuronal Guidance Growth by Aminated Graphene Oxide via Netrin-1/Deleted in Colorectal Cancer Signaling.

    abstract::Promotion of neurite outgrowth and synapse formation is a key step for nervous tissue regeneration. It is important for finding a new biomaterial to guide neuron growth to target neurons. Aminated graphene oxide (NH2-GO) displays electrical properties and dispersibility, which may change the surface charge of neurons ...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.9b00625

    authors: Liu M,Huang C,Jia Z,Zhao Z,Xiao X,Wang A,Li P,Guan X,Zhou G,Fan Y

    更新日期:2020-02-19 00:00:00

  • An azobenzene photoswitch sheds light on turn nucleation in amyloid-β self-assembly.

    abstract::Amyloid-β (Aβ) self-assembly into cross-β amyloid fibrils is implicated in a causative role in Alzheimer's disease pathology. Uncertainties persist regarding the mechanisms of amyloid self-assembly and the role of metastable prefibrillar aggregates. Aβ fibrils feature a sheet-turn-sheet motif in the constituent β-stra...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/cn2001188

    authors: Doran TM,Anderson EA,Latchney SE,Opanashuk LA,Nilsson BL

    更新日期:2012-03-21 00:00:00