Abstract：
:Recent evidence suggests an early involvement of dopaminergic (DA) processes and terminals in Parkinson's disease (PD). The arborization of neurons depends on the actin cytoskeleton, which in turn is regulated by small GTPases of the Rho family, encompassing Rho, Rac and Cdc42 subfamilies. Indeed, some reports point to a role for Rac and Cdc42 signaling in the pathophysiology of inherited parkinsonisms. We thus investigated the potential therapeutic effect of the modulation of cerebral Rho GTPases in PD. Cytotoxic necrotizing factor 1 (CNF1), a 114 kDa protein toxin produced by Escherichia coli, permanently activates RhoA, Rac1 and Cdc42 in intact cells. We report that the modulation of Rho GTPases by CNF1 results in hypertrophy of DA cell processes of cultured substantia nigra neurons, including increase in length, branching and varicosity. In vivo, the treatment corrects long-standing motor and biochemical asymmetries and restores degenerated nigrostriatal DA tissue after 6-hydroxydopamine lesion. We conclude that the pharmacological modulation of Rho GTPases shows neurorestorative potential and represents a promising avenue in the treatment PD. The study also suggests that naturally occurring molecules acting on Rho GTPase signaling, such as some bacterial protein toxins, might play a role in the development of PD.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Musilli M,Ciotti MT,Pieri M,Martino A,Borrelli S,Dinallo V,Diana Gdoi
10.1016/j.neuropharm.2016.06.016subject
Has Abstractpub_date
2016-10-01 00:00:00pages
357-365eissn
0028-3908issn
1873-7064pii
S0028-3908(16)30269-6journal_volume
109pub_type
杂志文章abstract：:Following its binding to somatodendritic receptors, the neuropeptide neurotensin (NT) internalizes via a clathrin-mediated process. In the present study, we investigated whether NT also internalizes presynaptically using synaptosomes from rat neostriatum, a region in which NT1 receptors are virtually all presynaptic. ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(02)00054-0
更新日期：2002-06-01 00:00:00
abstract：:Mechanisms underlying the neuroprotective properties of the weak MAO-A inhibitor moclobemide are not understood. Increasing evidence suggests that a moderate increase in intracellular free protons may contribute to neuroprotective properties due to a proton-mediated decrease in neuronal activity. Therefore, we studied...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(00)00033-2
更新日期：2000-08-23 00:00:00
abstract：:This review will provide an overview of the non-drug based approaches that have been demonstrated to enhance cognitive function of the compromised brain, primarily focussed on the two most widely adopted paradigms of environmental enrichment and enhanced physical exercise. Environmental enrichment involves the generat...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2012.06.029
更新日期：2013-01-01 00:00:00
abstract：:Efflux of exogenous [3H]taurine from superfused slices of cerebral cortex of rat was enhanced by the calcium chelators EDTA and EGTA and by large concentrations of unlabelled taurine and histidine. The enhancement by EDTA and EGTA could be totally blocked by excess calcium, but that by the amino acids only partially. ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(84)90202-8
更新日期：1984-03-01 00:00:00
abstract：:The modulation of insect behavior for the purpose of controlling the spread of infectious diseases has been the task of a few insect repellents for which the mechanistic modes of action on odorant receptors (ORs) are unclear. Here, we study the effects of the repellents DEET and IR3535, and a novel OR co-receptor (Orc...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2012.01.004
更新日期：2012-04-01 00:00:00
abstract：:This study investigated the structure-activity relationships and kinetic properties of a library of kynurenate analogues as inhibitors of 3H-L-glutamate transport into rat forebrain synaptic vesicles. The lack of inhibitory activity observed with the majority of the monocyclic pyridine derivatives suggested that the s...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(98)00080-x
更新日期：1998-07-01 00:00:00
abstract：:Several studies on humans and mice support oxytocin's role in improving social behaviour, but its use in pharmacotherapy presents some important limiting factors. To date, it is emerging a pharmacological potential for melanocortin 4 receptor (MC4R) agonism in social deficits treatment. Recently, we demonstrated that ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2018.02.007
更新日期：2018-05-01 00:00:00
abstract：:4-Phenyl-1,2,3,4-tetrahydroisoquinoline (4-PTIQ) has previously been shown to have antagonistic properties to methamphetamine in the spinal cord. Administration of 4-PTIQ (5 mg/kg, s.c.) reduced the ambulation induced by methamphetamine (0.5 mg/kg, s.c.) in rats. Methamphetamine (3 micrograms), injected unilaterally i...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(93)90107-e
更新日期：1993-03-01 00:00:00
abstract：:The ability of (-)N-n-propylnorapomorphine and selective D1 and D2 dopamine receptor agonists and antagonists to modify the release of [3H]dopamine, induced by potassium from the nucleus accumbens, was studied using an in vitro superfusion technique. (-)N-n-Propylnorapomorphine, in picomolar concentrations, inhibited ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(90)90090-e
更新日期：1990-04-01 00:00:00
abstract：:The purpose of the present studies was to investigate the behavioral and convulsant effects produced by the group I metabotropic glutamate receptor agonist (S)-3,5-dihydroxyphenylglycine (DHPG). Administered i.c.v. to mice, (S)-3,5-DHPG produced a behavioral syndrome consisting of scratching and/or facial grooming, tr...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2005.01.017
更新日期：2005-05-01 00:00:00
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
更新日期：1993-07-01 00:00:00
abstract：:Mu-opioid and CB1-cannabinoid agonists produce analgesia; however, adverse effects limit use of drugs in both classes. Additive or synergistic effects resulting from concurrent administration of low doses of mu- and CB1-agonists may produce analgesia with fewer side effects. Synergism potentially results from interact...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2012.06.046
更新日期：2012-10-01 00:00:00
abstract：:Serotonin (5-HT) neurons are involved in wake promotion and exert a strong inhibitory influence on rapid eye movement (REM) sleep. Such effects have been ascribed, at least in part to the action of 5-HT at post-synaptic 5-HT1A receptors (5-HT1AR) in the brainstem, a major wake/REM sleep regulatory center. However, the...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2018.06.014
更新日期：2018-08-01 00:00:00
abstract：:Phosphodiesterase 2 (PDE2) plays an important role in treatment of stress-related depression through regulation of antioxidant defense and neuroprotective mechanisms. However, the causal relationship between PDE2 and the prevalence of depression and anxiety upon exposure to oxidative stress has not been investigated. ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2018.09.039
更新日期：2018-12-01 00:00:00
abstract：:The identification and characterization of amyloid-beta (Abeta) and tau as the main pathological substrates of Alzheimer's disease (AD) have driven many efforts in search for suitable biomarkers for AD. In the last decade, research in this area has focused on developing a better understanding of the principles that go...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2010.04.006
更新日期：2010-09-01 00:00:00
abstract：:Absence epilepsy is generated by the cortico-thalamo-cortical network, which undergoes a finely tuned regulation by metabotropic glutamate (mGlu) receptors. We have shown previously that potentiation of mGlu1 receptors reduces spontaneous occurring spike and wave discharges (SWDs) in the WAG/Rij rat model of absence e...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2012.05.044
更新日期：2013-03-01 00:00:00
abstract：:γ-Aminobutyric acid B (GABAB) receptors and their ligands are postulated as potential therapeutic targets for the treatment of several brain disorders, including drug dependence. Over the past fifteen years positive allosteric modulators (PAMs) have emerged that enhance the effects of GABA at GABAB receptors and which...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2014.06.016
更新日期：2015-01-01 00:00:00
abstract：:We investigated block of voltage-dependent Ca channels in freshly dissociated rat central and peripheral neurons by the synthetic peptide omega-Aga-IVA. Synthetic omega-Aga-IVA blocked approximately 90% of the high-threshold Ca current in cerebellar Purkinje neurons with an estimated Kd of approximately 1.5 nM, slight...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(93)90010-z
更新日期：1993-11-01 00:00:00
abstract：:In PC12 cells, isosorbide dinitrate (ISDN) and S-nitrosol-acetyl-penicillamine (SNAP), both nitric oxide (NO) generators, attenuated K+ (56 mM)-stimulated release of dopamine. The attenuation was not observed with isosorbide, an ISDN analog lacking NO generating capacity. In this model, A23187 (Ca2+ ionophore), Bay K8...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(94)00151-h
更新日期：1995-02-01 00:00:00
abstract：:Histamine is an aminergic neurotransmitter, which regulates wakefulness, arousal and attention in the central nervous system. Histamine receptors have been the target of efforts to develop pro-cognitive drugs to treat disorders such as Alzheimer's disease and schizophrenia. Cognitive functions including attention are ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2017.03.003
更新日期：2017-05-15 00:00:00
abstract：:In the human genome, 22 genes are coding for the class C G protein-coupled receptors that are receptors for the two main neurotransmitters glutamate and γ-aminobutyric acid, for Ca(2+) and for sweet and amino acid taste compounds. In addition to the GPCR heptahelical transmembrane domain responsible for G-protein acti...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2010.08.009
更新日期：2011-01-01 00:00:00
abstract：INTRODUCTION:The aim of the study was to clarify the dose response for inhibition of catechol-O-methyltransferase (COMT) by opicapone, a third generation COMT inhibitor, after acute and repeated administration to the cynomolgus monkey with pharmacokinetic evaluation at the higher dose. METHODS:Three cynomolgus monkeys...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2018.10.001
更新日期：2018-12-01 00:00:00
abstract：BACKGROUND:Bipolar disorder (BD) mania patients exhibit poor cognition and reward-seeking/hypermotivation, negatively impacting a patient's quality of life. Current treatments (e.g., lithium), do not treat such deficits. Treatment development has been limited due to a poor understanding of the neural mechanisms underly...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2016.07.030
更新日期：2017-02-01 00:00:00
abstract：:Several psychiatric disorders involving the prefrontal cortex (PFC) are associated with a dysfunction of 5-HT(1A) receptors (5-HT(1A)R). These receptors, located on interneurons and pyramidal neurons, may influence neuronal excitability through a regulation of the balance between excitation (E) and inhibition (I). Pat...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2013.03.003
更新日期：2013-08-01 00:00:00
abstract：:Ionic currents from non-inactivating Shaker K(+)-channels were expressed in Xenopus oocytes and recorded with the cut-open oocyte voltage clamp technique. Kinetic properties of ionic currents were studied between 1.4 and 19 degrees C. The forward step of the last transition (...C --> O) of the activation pathway, just...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(96)00111-6
更新日期：1996-01-01 00:00:00
abstract：:Alzheimer's disease (AD) is the most common cause of dementia, clinically characterized by loss of memory and progressive deficits in different cognitive domains. An emerging disease-modifying approach to face the multifactorial nature of AD may be represented by the development of Multi-Target Directed Ligands (MTDLs...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2011.10.007
更新日期：2012-02-01 00:00:00
abstract：:Stress-related psychiatric disorders, including anxiety, are complex diseases that have genetic, and environmental causes. Stressful experiences increase the release of prefrontal amygdala neurotransmitters, a response that is relevant to cognitive, emotional, and behavioral coping. Moreover, exposure to stress elicit...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2016.03.044
更新日期：2016-08-01 00:00:00
abstract：:Changes in brain reward and control systems of frontal cortical areas including the orbitofrontal cortex (OFC) are associated with alcohol use disorders (AUD). The OFC is extensively innervated by monoamines, and drugs that target monoamine receptors have been used to treat a number of neuropsychiatric diseases, inclu...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2018.04.019
更新日期：2018-07-15 00:00:00
abstract：:Alcohol use disorder (AUD) affects all sexes, however women who develop AUD may be particularly susceptible to cravings and other components of the disease. While many brain regions are involved in AUD etiology, proper prefrontal cortex (PFC) function is particularly important for top-down craving management and the m...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2020.108126
更新日期：2020-11-01 00:00:00
abstract：:Gene-environment interactions drive experience-dependent changes in the brain that alter cognition, emotion and behaviour. Positive engagement with the environment, through novel experience and physical activity, can improve brain function, although the mechanisms mediating such experience-dependent plasticity remain ...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2017.12.038
更新日期：2019-02-01 00:00:00
