Prioritizing the development of mouse models for childhood brain disorders.

Abstract:

:Mutations in hundreds of genes contribute to cognitive and behavioral dysfunction associated with developmental brain disorders (DBDs). Due to the sheer number of risk factors available for study combined with the cost of developing new animal models, it remains an open question how genes should be prioritized for in-depth neurobiological investigations. Recent reviews have argued that priority should be given to frequently mutated genes commonly found in sporadic DBD patients. Intrigued by this idea, we explored to what extent "high priority" risk factors have been studied in animals in an effort to assess their potential for generating valuable preclinical models capable of advancing the neurobiological understanding of DBDs. We found that in-depth whole animal studies are lacking for many high priority genes, with relatively few neurobiological studies performed in construct valid animal models aimed at understanding the pathological substrates associated with disease phenotypes. However, some high priority risk factors have been extensively studied in animal models and they have generated novel insights into DBD patho-neurobiology while also advancing early pre-clinical therapeutic treatment strategies. We suggest that prioritizing model development toward genes frequently mutated in non-specific DBD populations will accelerate the understanding of DBD patho-neurobiology and drive novel therapeutic strategies. This article is part of the Special Issue entitled 'Synaptopathy--from Biology to Therapy'.

journal_name

Neuropharmacology

journal_title

Neuropharmacology

authors

Ogden KK,Ozkan ED,Rumbaugh G

doi

10.1016/j.neuropharm.2015.07.029

subject

Has Abstract

pub_date

2016-01-01 00:00:00

pages

2-16

eissn

0028-3908

issn

1873-7064

pii

S0028-3908(15)30036-8

journal_volume

100

pub_type

杂志文章,评审
  • Serotonergic dorsal raphe neurons: subsensitivity to amphetamine with long-term treatment.

    abstract::Rats were pretreated twice daily for six consecutive days with either saline or 1.0, 5.0, or 10.0 mg/kg (+)-amphetamine. On the following day, single-unit recording techniques were used to identify serotonin-containing neurons in the dorsal raphe nucleus (DRN). Pretreatment with amphetamine did not alter the mean spon...

    journal_title:Neuropharmacology

    pub_type: 杂志文章

    doi:10.1016/0028-3908(87)90233-4

    authors: Heidenreich BA,Basse-Tomusk AE,Rebec GV

    更新日期:1987-07-01 00:00:00

  • Analysis by HPLC-EC of metabolites of monoamines in fetal and postnatal rat brain.

    abstract::High performance liquid chromatography with electrochemical detection (HPLC-EC) was adapted for the analysis of metabolites of monoamines (MA) in the developing brain of the rat. 3-Methoxy-4-hydroxy-phenyl-ethylene glycol (MOPEG), dihydroxy phenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxy-3-indoleaceti...

    journal_title:Neuropharmacology

    pub_type: 杂志文章

    doi:10.1016/0028-3908(86)90191-7

    authors: Ribary U,Schlumpf M,Lichtensteiger W

    更新日期:1986-09-01 00:00:00

  • Glutamate transport system as a key constituent of glutamosome: Molecular pathology and pharmacological modulation in chronic pain.

    abstract::Neural uptake of glutamate is executed by the structurally related members of the SLC1A family of solute transporters: GLAST/EAAT1, GLT-1/EAAT2, EAAC1/EAAT3, EAAT4, ASCT2. These plasma membrane proteins ensure supply of glutamate, aspartate and some neutral amino acids, including glutamine and cysteine, for synthetic,...

    journal_title:Neuropharmacology

    pub_type: 杂志文章,评审

    doi:10.1016/j.neuropharm.2019.04.029

    authors: Gegelashvili G,Bjerrum OJ

    更新日期:2019-12-15 00:00:00

  • The effects of adrenalectomy and ovariectomy on the behavioral and hypothermic responses of rats to 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT).

    abstract::The aim of this study was to determine the effects of sex, corticosterone and oestradiol-17 beta on the hypothermia and motor behavioural syndrome induced by the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) in the rat. The hypothermia, but not the behavioural syndrome induced by 8-OH-DPAT...

    journal_title:Neuropharmacology

    pub_type: 杂志文章

    doi:10.1016/0028-3908(93)90078-h

    authors: Young AH,Dow RC,Goodwin GM,Fink G

    更新日期:1993-07-01 00:00:00

  • Brain allopregnanolone regulates the potency of the GABA(A) receptor agonist muscimol.

    abstract::Allopregnanolone (ALLO), a potent positive-allosteric modulator of the action of GABA at GABA(A) receptors, is synthesized in the brain from progesterone by the sequential action of two enzymes: 5alpha-reductase and 3alpha-hydroxysteroidoxidoreductase. The concentration of ALLO in various parts of the mouse brain vari...

    journal_title:Neuropharmacology

    pub_type: 杂志文章

    doi:10.1016/s0028-3908(99)00149-5

    authors: Pinna G,Uzunova V,Matsumoto K,Puia G,Mienville JM,Costa E,Guidotti A

    更新日期:2000-01-28 00:00:00

  • Inhibition of the morphine withdrawal syndrome and the development of physical dependence by lithium in mice.

    abstract::Due to the claim that lithium (Li+) reduces morphine self-administration in dependent rats, the effects of acute and chronic Li+ treatments on naloxone-precipitated withdrawal syndrome and physical dependence development to morphine in mice chronically treated with morphine, were evaluated. Morphine dependency was ind...

    journal_title:Neuropharmacology

    pub_type: 杂志文章

    doi:10.1016/0028-3908(94)00121-8

    authors: Dehpour AR,Farsam H,Azizabadi-Farahani M

    更新日期:1995-01-01 00:00:00

  • Neurogenic hypertension after depletion of norepinephrine in anterior hypothalamus induced by 6-hydroxydopamine administration into the ventral pons: role of serotonin.

    abstract::Destruction of the ventral noradrenergic pathway elicited by administration of 6-hydroxydopamine (6-OHDA, 5 micrograms into each side of the ventral pons) reduced the content of norepinephrine (NE) in the anterior hypothalamus (-80%) and induced an increase in arterial blood pressure (ABP) and in heart rate. These hyp...

    journal_title:Neuropharmacology

    pub_type: 杂志文章

    doi:10.1016/0028-3908(83)90257-5

    authors: Benarroch EE,Balda MS,Finkielman S,Nahmod VE

    更新日期:1983-01-01 00:00:00

  • The N-terminal domain of the GluN3A subunit determines the efficacy of glycine-activated NMDA receptors.

    abstract::N-methyl-d-aspartate (NMDA) receptors composed of glycine-binding GluN1 and GluN3 subunits function as excitatory glycine receptors that respond to agonist application only with a very low efficacy. Binding of glycine to the high-affinity GluN3 subunits triggers channel opening, whereas glycine binding to the low-affi...

    journal_title:Neuropharmacology

    pub_type: 杂志文章

    doi:10.1016/j.neuropharm.2016.01.014

    authors: Mesic I,Madry C,Geider K,Bernhard M,Betz H,Laube B

    更新日期:2016-06-01 00:00:00

  • Introduction of the 5-HT3B subunit alters the functional properties of 5-HT3 receptors native to neuroblastoma cells.

    abstract::The identification of a second 5-HT(3) (5-HT(3B)) subunit provides an explanation for 5-HT(3) receptor heterogeneity. We investigated whether introduction of recombinant 5-HT(3B) subunits would alter the functional properties of mouse neuroblastoma 5-HT(3) receptors. RT-PCR analysis revealed that NB41A3 cells contain ...

    journal_title:Neuropharmacology

    pub_type: 杂志文章

    doi:10.1016/s0028-3908(02)00376-3

    authors: Stewart A,Davies PA,Kirkness EF,Safa P,Hales TG

    更新日期:2003-02-01 00:00:00

  • Functional modulation of G-protein coupled receptors during Parkinson disease-like neurodegeneration.

    abstract::G-protein coupled dopamine and metabotropic glutamate receptors (mGlu) can modulate neurotransmission during Parkinson's disease (PD)-like neurodegeneration. PET imaging studies in a unilateral dopamine denervation model (6-OHDA) showed a significant inverse correlation of presynaptic mGlu4 and postsynaptic mGlu5 expr...

    journal_title:Neuropharmacology

    pub_type: 杂志文章

    doi:10.1016/j.neuropharm.2015.11.010

    authors: Jenkins BG,Zhu A,Poutiainen P,Choi JK,Kil KE,Zhang Z,Kuruppu D,Aytan N,Dedeoglu A,Brownell AL

    更新日期:2016-09-01 00:00:00

  • When a good taste turns bad: Neural mechanisms underlying the emergence of negative affect and associated natural reward devaluation by cocaine.

    abstract::An important feature of cocaine addiction in humans is the emergence of negative affect (e.g., dysphoria, irritability, anhedonia), postulated to play a key role in craving and relapse. Indeed, the DSM-IV recognizes that social, occupational and/or recreational activities become reduced as a consequence of repeated dr...

    journal_title:Neuropharmacology

    pub_type: 杂志文章,评审

    doi:10.1016/j.neuropharm.2013.04.025

    authors: Carelli RM,West EA

    更新日期:2014-01-01 00:00:00

  • Inhibition of PDE2 and PDE4 synergistically improves memory consolidation processes.

    abstract::Phosphodiesterases (PDE) are the only enzymes that degrade cAMP and cGMP which are second messengers crucial to memory consolidation. Different PDE inhibitors have been developed and tested for their memory-enhancing potential, but the occurrence of side effects has hampered clinical progression. As separate inhibitio...

    journal_title:Neuropharmacology

    pub_type: 杂志文章

    doi:10.1016/j.neuropharm.2020.108414

    authors: Paes D,Xie K,Wheeler DG,Zook D,Prickaerts J,Peters M

    更新日期:2021-02-15 00:00:00

  • Stereospecific antagonism by (+)-alpha-methyl-4-carboxyphenylglycine (MCPG) of (1S,3R)-ACPD-induced effects in neonatal rat motoneurones and rat thalamic neurones.

    abstract::The (+)-enantiomer of alpha-methyl-4-carboxyphenylglycine (MCPG) stereoslectively antagonized the depolarization of neonatal rat motoneurones and the excitation of rat thalamic neurons induced by the specific metabotropic glutamate receptor agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate (ACPD). (+)-MCPG prefere...

    journal_title:Neuropharmacology

    pub_type: 杂志文章

    doi:10.1016/0028-3908(93)90088-k

    authors: Jane DE,Jones PL,Pook PC,Salt TE,Sunter DC,Watkins JC

    更新日期:1993-07-01 00:00:00

  • Acute administration of nicotine increases the in vivo extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid and ascorbic acid preferentially in the nucleus accumbens of the rat: comparison with caudate-putamen.

    abstract::Using in vivo dialysis and voltammetry, the effect of acute administration of (-)-nicotine (0.8 mg/kg free base, s.c.) on extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid, 5-hydroxy-indoleacetic acid and ascorbic acid in the nucleus accumbens and caudate-putamen of chloral hydrate-anaesthetised rats ha...

    journal_title:Neuropharmacology

    pub_type: 杂志文章

    doi:10.1016/0028-3908(90)90042-p

    authors: Brazell MP,Mitchell SN,Joseph MH,Gray JA

    更新日期:1990-12-01 00:00:00

  • Amphetamine and alpha-methyl-p-tyrosine affect the exercise-induced imbalance between the availability of tryptophan and synthesis of serotonin in the brain of the rat.

    abstract::This study was performed to investigate the effects of exercise on the synthesis of dopamine (DA) and 5-hydroxytryptamine (5-HT) in the brain of the trained rat. The consequences on the relationships between these two systems were also examined. The sum of the levels of free 3,4-dihydroxyphenyl acetic acid (DOPAC) plu...

    journal_title:Neuropharmacology

    pub_type: 杂志文章

    doi:10.1016/0028-3908(87)90254-1

    authors: Chaouloff F,Laude D,Merino D,Serrurrier B,Guezennec Y,Elghozi JL

    更新日期:1987-08-01 00:00:00

  • Proconvulsant and anticonvulsant effects in mice of acute and chronic treatment with cocaine.

    abstract::The proconvulsant and anticonvulsant effects of acute and chronic exposure to cocaine were investigated in adult, male, CF-1 mice. The proconvulsant effects of cocaine in mice only manifested themselves after daily exposure to motor-stimulant doses. Although daily treatment decreased electroshock convulsion threshold,...

    journal_title:Neuropharmacology

    pub_type: 杂志文章

    doi:10.1016/0028-3908(89)90155-x

    authors: Karler R,Petty C,Calder L,Turkanis SA

    更新日期:1989-07-01 00:00:00

  • Neuroprotective effects of ginsenoside Rg1 through the Wnt/β-catenin signaling pathway in both in vivo and in vitro models of Parkinson's disease.

    abstract::Ginsenoside Rg1 (Rg1) is a major bioactive ingredient in Panax ginseng that has low toxicity and has been shown to have neuroprotective effects. The objectives of the present study were to explore the potential of the application of Rg1 for the treatment of Parkinson's disease (PD) and to determine whether its neuropr...

    journal_title:Neuropharmacology

    pub_type: 杂志文章

    doi:10.1016/j.neuropharm.2015.10.024

    authors: Zhou T,Zu G,Zhang X,Wang X,Li S,Gong X,Liang Z,Zhao J

    更新日期:2016-02-01 00:00:00

  • Developmental regulation of expression of GABAA receptor alpha 1 and alpha 6 subunits in cultured rat cerebellar granule cells.

    abstract::We have studied the postnatal development of GABAA receptor alpha 1 and alpha 6 subunits expressed by primary cultures of cerebellar granule cells originating from 2-day-old (postnatal day 2, P2) and 10-day-old (P10) rat neonates. At these ages, the granule cells are at distinct stages of cerebellar development. In bo...

    journal_title:Neuropharmacology

    pub_type: 杂志文章

    doi:10.1016/s0028-3908(96)00114-1

    authors: Thompson CL,Pollard S,Stephenson FA

    更新日期:1996-01-01 00:00:00

  • Necessary, but not sufficient: insights into the mechanisms of mGluR mediated long-term depression from a rat model of early life seizures.

    abstract::Using the rat model of early life seizures (ELS), which has exaggerated mGluR mediated long-term depression of synaptic strength (mGluR-LTD) in adulthood, we probed the signaling cascades underlying mGluR-LTD induction. Several inhibitors completely blocked mGluR-LTD in control but not in ELS rats: the proteasome, the...

    journal_title:Neuropharmacology

    pub_type: 杂志文章

    doi:10.1016/j.neuropharm.2014.04.011

    authors: Bernard PB,Castano AM,Bayer KU,Benke TA

    更新日期:2014-09-01 00:00:00

  • Investigation of the presynaptic effects of quinine and quinidine on the release and uptake of monoamines in rat brain tissue.

    abstract::Quinine and quinidine are reported to potentiate the behavioural effects of serotonergic agents and monoamine uptake inhibitors. We have therefore investigated the presynaptic actions of quinine and quinidine on monoamine uptake and release in rat brain tissue in vitro. Quinidine evoked the release of [3H]5-HT, [3H]no...

    journal_title:Neuropharmacology

    pub_type: 杂志文章

    doi:10.1016/s0028-3908(98)00075-6

    authors: Clement EM,Grahame-Smith DG,Elliott JM

    更新日期:1998-07-01 00:00:00

  • Endogenous and synthetic neuroactive steroids evoke sustained increases in the efficacy of GABAergic inhibition via a protein kinase C-dependent mechanism.

    abstract::The neuroactive steroid (NAS) tetrahydrodeoxycorticosterone (THDOC) increases protein kinase C (PKC) mediated phosphorylation of extrasynaptic GABAA receptor (GABAAR) subunits leading to increased surface expression of α4/β3 subunit-containing extrasynaptic GABAARs, leading to a sustained increase in GABAAR tonic curr...

    journal_title:Neuropharmacology

    pub_type: 杂志文章

    doi:10.1016/j.neuropharm.2016.10.010

    authors: Modgil A,Parakala ML,Ackley MA,Doherty JJ,Moss SJ,Davies PA

    更新日期:2017-02-01 00:00:00

  • Biochemical profile of YM992, a novel selective serotonin reuptake inhibitor with 5-HT2A receptor antagonistic activity.

    abstract::YM992, (S)-2-[[(7-fluoro-4-indanyl)oxy]methyl]morpholine monohydrochloride, exhibited the biochemical profile of a selective serotonin (5-HT) reuptake inhibitor (SSRI) with 5-HT2A receptor antagonistic activity. YM922 showed the same high affinity as fluoxetine against the 5-HT reuptake site (Ki = 21 nM) and a similar...

    journal_title:Neuropharmacology

    pub_type: 杂志文章

    doi:10.1016/s0028-3908(96)00079-2

    authors: Hatanaka K,Nomura T,Hidaka K,Takeuchi H,Yatsugi S,Fujii M,Yamaguchi T

    更新日期:1996-01-01 00:00:00

  • Pharmacological treatment of tic disorders and Tourette Syndrome.

    abstract::The present review gives an overview of current pharmacological treatment options of tic disorders and Tourette Syndrome (TS). After a short summary on phenomenology, clinical course and comorbid conditions we review indications for pharmacological treatment in detail. Unfortunately, standardized and large enough drug...

    journal_title:Neuropharmacology

    pub_type: 杂志文章,评审

    doi:10.1016/j.neuropharm.2012.05.043

    authors: Roessner V,Schoenefeld K,Buse J,Bender S,Ehrlich S,Münchau A

    更新日期:2013-05-01 00:00:00

  • High ethanol sensitive glycine receptors regulate firing in D1 medium spiny neurons in the nucleus accumbens.

    abstract::Inhibitory glycine receptors (GlyRs) are widely expressed in spinal cord and brain stem. They are also expressed in the nucleus Accumbens (nAc) where they have been implicated in the release of dopamine from the ventral tegmental area to the nAc in the presence of ethanol. One of the major types of neurons in the nAc ...

    journal_title:Neuropharmacology

    pub_type: 杂志文章

    doi:10.1016/j.neuropharm.2019.107773

    authors: Gallegos S,Muñoz B,Araya A,Aguayo LG

    更新日期:2019-12-01 00:00:00

  • Post-pubertal adrenergic changes in rats with neonatal lesions of the ventral hippocampus.

    abstract::Lesions of the ventral hippocampus (VH) in neonatal rats result in post-pubertal alterations in a number of cognitive, social and motor behaviors that bear some analogy to schizophrenia. Increased sensitivity to stress and psychostimulants and prefrontal functional changes in the lesioned animals suggest an involvemen...

    journal_title:Neuropharmacology

    pub_type: 杂志文章

    doi:10.1016/j.neuropharm.2003.08.001

    authors: Bhardwaj SK,Quirion R,Srivastava LK

    更新日期:2004-01-01 00:00:00

  • Blockade of apomorphine-induced yawning in rats by the dopamine autoreceptor antagonist (+)-AJ 76.

    abstract::The effects of the putative, selective dopamine autoreceptor antagonist (+)-AJ 76 on yawning, penile grooming and mouth movements induced by small doses of apomorphine in male rats were examined. Yawning induced by 0.05mg/kg apomorphine was dose dependently blocked by (+)-AJ-76, significant decreases being observed at...

    journal_title:Neuropharmacology

    pub_type: 杂志文章

    doi:10.1016/0028-3908(89)90021-x

    authors: Dourish CT,Herbert EN,Iversen SD

    更新日期:1989-12-01 00:00:00

  • 11,12 -Epoxyeicosatrienoic acid (11,12 EET) reduces excitability and excitatory transmission in the hippocampus.

    abstract::Recent studies suggest a role for the arachidonic acid-derived epoxyeicosatrienoic acids (EETs) in attenuating epileptic seizures. However, their effect on neurotransmission has never been investigated in detail. Here, we studied how 11,12- and 14,15 EET affect excitability and excitatory neurotransmission in mouse hi...

    journal_title:Neuropharmacology

    pub_type: 杂志文章

    doi:10.1016/j.neuropharm.2017.05.013

    authors: Mule NK,Orjuela Leon AC,Falck JR,Arand M,Marowsky A

    更新日期:2017-09-01 00:00:00

  • Spike-timing dependent plasticity in striatal interneurons.

    abstract::Basal ganglia, an ensemble of interconnected subcortical nuclei, are involved in adaptive motor planning and procedural learning. Striatum, the primary input nucleus of basal ganglia, extracts the pertinent cortical and thalamic information from background noise in relation with the environmental stimuli and motivatio...

    journal_title:Neuropharmacology

    pub_type: 杂志文章,评审

    doi:10.1016/j.neuropharm.2011.01.023

    authors: Fino E,Venance L

    更新日期:2011-04-01 00:00:00

  • Transient increase in alcohol self-administration following a period of chronic exposure to corticosterone.

    abstract::Stressful life events and chronic stressors have been associated with escalations in alcohol drinking. Stress exposure leads to the secretion of glucocorticoids (cortisol in the human; corticosterone (CORT) in the rodent). To model a period of heightened elevations in CORT, the present work assessed the effects of chr...

    journal_title:Neuropharmacology

    pub_type: 杂志文章

    doi:10.1016/j.neuropharm.2013.04.036

    authors: Besheer J,Fisher KR,Lindsay TG,Cannady R

    更新日期:2013-09-01 00:00:00

  • Role of PPAR-β/δ/miR-17/TXNIP pathway in neuronal apoptosis after neonatal hypoxic-ischemic injury in rats.

    abstract::Activation of peroxisome proliferator-activated receptor beta/delta (PPAR-β/δ), a nuclear receptor acting as a transcription factor, was shown to be protective in various models of neurological diseases. However, there is no information about the role of PPAR-β/δ as well as its molecular mechanisms in neonatal hypoxia...

    journal_title:Neuropharmacology

    pub_type: 杂志文章

    doi:10.1016/j.neuropharm.2018.08.003

    authors: Gamdzyk M,Doycheva DM,Malaguit J,Enkhjargal B,Tang J,Zhang JH

    更新日期:2018-09-15 00:00:00