Abstract：
:At times of an aging population and increasing prevalence of neurodegenerative disorders, effective medical treatments remain limited. Therefore, there is an urgent need for new therapies to treat Alzheimer's disease (AD). Deep brain stimulation (DBS) is thought to address the neuronal network dysfunction of this disorder and may offer new therapeutic options. Preliminary evidence suggests that DBS of the fornix may have effects on cognitive decline, brain glucose metabolism, hippocampal volume and cortical grey matter volume in certain patients with mild AD. Rodent studies have shown that increase of cholinergic neurotransmitters, hippocampal neurogenesis, synaptic plasticity and reduction of amyloid plaques are associated with DBS. Currently a large phase III study of fornix DBS is assessing efficacy in patients with mild AD aged 65 years and older. The Nucleus basalis of Meynert has also been explored in a phase I study in of mild to moderate AD and was tolerated well regardless of the lack of benefit. Being an established therapy for Parkinson's Disease (PD), DBS may exert some disease-modifying traits rather than being a purely symptomatic treatment. There is evidence of dopaminergic neuroprotection in animal models and some suggestion that DBS may influence the natural progression of the disorder. Neuromodulation may possibly have beneficial effects on course of different neurodegenerative disorders compared to medical therapy alone. For dementias, functional neurosurgery may provide an adjunctive option in patient care. This article is part of the special issue entitled 'The Quest for Disease-Modifying Therapies for Neurodegenerative Disorders'.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Jakobs M,Lee DJ,Lozano AMdoi
10.1016/j.neuropharm.2019.107860subject
Has Abstractpub_date
2020-07-01 00:00:00pages
107860eissn
0028-3908issn
1873-7064pii
S0028-3908(19)30426-5journal_volume
171pub_type
杂志文章,评审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：:More studies are required to develop therapeutic agents for treating spinocerebellar ataxia type 3 (SCA3), which is caused by mutant polyglutamine-expanded ataxin-3 and is the most prevalent subtype of spinocerebellar ataxias. T1-11 [N6-(4-Hydroxybenzyl) adenosine], isolated from a Chinese medicinal herb Gastordia ela...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2015.08.009
更新日期：2015-12-01 00:00:00
abstract：:Somatostatin (SRIF) is involved in a variety of physiological functions via the activation of five subtypes of specific receptors (sst1-5). Here, we investigated the effects of SRIF on AMPA receptor (AMPAR)-mediated currents (AMPA currents) in isolated rat retinal ganglion cells (GCs) using patch-clamp techniques. Imm...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2016.03.006
更新日期：2016-08-01 00:00:00
abstract：:The responses of the guinea-pig ileum myenteric plexus-longitudinal muscle to the food, drug and cosmetic dye erythrosin B (FD & C Red No. 3) were examined in acetylcholine- and electrically-stimulated preparations. Erythrosin B (10(-6)-10(-4)) reduced the amplitude of the mechanical responses produced by both stimuli...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(83)90001-1
更新日期：1983-02-01 00:00:00
abstract：:Muscarinic acetylcholine receptors (mAChRs) are G proteincoupled receptors (GPCRs) that mediate the metabotropic actions of acetylcholine (ACh). There are five subtypes of mAChR, M1 - M5, which are expressed throughout the central nervous system (CNS) on numerous cell types and represent promising treatment targets fo...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2017.11.018
更新日期：2018-07-01 00:00:00
abstract：:Depolarizing, hyperpolarizing and biphasic muscarinic responses have been described in hippocampal inhibitory interneurons, but the receptor subtypes and activity patterns required to synaptically activate muscarinic responses in interneurons have not been completely characterized. Using optogenetics combined with who...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2013.05.026
更新日期：2013-10-01 00:00:00
abstract：:Studies with heterologous expression systems have shown that the α4β2 nicotinic acetylcholine receptor (nAChR) subtype can exist in two stoichiometries (with two [(α4)2(β2)3] or three [(α4)3(β2)2] copies of the α subunit in the receptor pentamer) which have different pharmacological and functional properties and are d...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2016.04.048
更新日期：2016-09-01 00:00:00
abstract：BACKGROUND AND OBJECTIVE:Hyperdopaminergic signaling and an upregulated brain arachidonic acid (AA) cascade may contribute to bipolar disorder (BD). Lithium and carbamazepine, FDA-approved for the treatment of BD, attenuate brain dopaminergic D(2)-like (D(2), D(3), and D(4)) receptor signaling involving AA when given c...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2011.07.025
更新日期：2011-12-01 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：:In nonhuman primates, anxiety levels are typically assessed by observing social hierarchies or behavior in an intruder task. As measures of anxiety might influence performance on a particular cognitive task, it is important to analyze these measures in the same room as used for the cognitive task. As we use a playroom...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2011.08.014
更新日期：2012-01-01 00:00:00
abstract：:The present study investigated the effects of WB4101, a selective alpha 1-adrenoceptor blocking agent, and idazoxan, a selective alpha 2-adrenoceptor blocking agent, on antinociception and sedation in the rat mediated by adrenoceptors. Selective alpha 1-adrenoceptor agonists, e.g. ST587 and methoxamine induced antinoc...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(86)90234-0
更新日期：1986-04-01 00:00:00
abstract：:The effect of various doses of tianeptine on the extracellular concentrations of dopamine was studied in the striatum and nucleus accumbens of the rat. At 5 (but not 2.5) mg/kg intraperitoneally, tianeptine increased the extracellular dopamine only in the nucleus accumbens. At 10 mg/kg, the effect was also seen in the...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(92)90171-k
更新日期：1992-03-01 00:00:00
abstract：:The effects of increased membrane cholesterol on the potentiation of GABA(A) currents by pregnanolone (5beta-pregnan-3alpha-ol-20-one), allopregnanolone (5alpha-pregnan-3alpha-ol-20-one), alphaxalone (5alpha-pregnan-3alpha-ol-11,20-dione) and propofol were investigated in acutely dissociated rat hippocampal neurones u...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(98)00113-0
更新日期：1998-09-01 00:00:00
abstract：:Brain inosine and hypoxanthine were measured in mice at intervals following the intraperitoneal injection of pentylenetetrazol (PTZ), 100 mg/kg. These purines increased only after myoclonic jerks appeared and were maximal at the time of tonic hindlimb extension. Phenytoin and phenobarbital, which prevent tonic hindlim...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(83)90161-2
更新日期：1983-05-01 00:00:00
abstract：:To investigate whether the reversible MAO-B inhibitor and sodium channel blocker safinamide impairs glutamate release under parkinsonian conditions in vivo, and this effect is dependent on MAO-B inhibition, safinamide (and rasagiline as a comparator) were administered to 6-hydroxydopamine hemilesioned rats, a model of...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2020.108006
更新日期：2020-05-01 00:00:00
abstract：:Tropomyosin (Tm) in non-muscle cells is involved in stabilisation of the actin cytoskeleton. Some of the 40 isoforms described are found in the brain and exhibit spatial and developmental regulation. Non-muscle isoforms from the gamma Tm gene can be subdivided into three subsets of isoforms differing at the C-terminus...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2004.07.011
更新日期：2004-10-01 00:00:00
abstract：:A number of pre-clinical studies have shown that brain-generated acetaldehyde, the first metabolite of ethanol, exerts reinforcing effects that promote the acquisition of ethanol intake, while chronic intake maintenance appears to be mediated by alcohol-induced brain neuroinflammation/oxidative stress. Recently, it wa...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2018.12.001
更新日期：2019-03-01 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：:Nicotine improves endotoxic manifestations of hypotension and cardiac autonomic dysfunction in rats. Here, we test the hypothesis that brainstem antiinflammatory pathways of α7/α4β2 nicotinic acetylcholine receptors (nAChRs) modulate endotoxic cardiovascular derangements. Pharmacologic and molecular studies were perfo...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2019.107683
更新日期：2019-10-01 00:00:00
abstract：:Increasingly in the realm of neurological disorders, particularly those involving neurodegeneration, mitochondrial dysfunction is emerging at the core of their pathogenic processes. Most of these diseases still lack effective treatment and are hampered by a shortfall in the development of novel medicines. Clearly new ...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2015.10.033
更新日期：2016-03-01 00:00:00
abstract：:BMS-763534 is a potent (CRF(1) IC(50) = 0.4 nM) and selective (>1000-fold selectivity vs. all other sites tested) CRF(1) receptor antagonist (pA2 = 9.47 vs. CRF(1)-mediated cAMP production in Y79 cells). BMS-763534 accelerated the dissociation of (125)I-o-CRF from rat frontal cortex membrane CRF(1) receptors consisten...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2012.10.025
更新日期：2013-04-01 00:00:00
abstract：:Chronic administration of desipramine resulted in a significant decrease in the degree of stimulation of production of cyclic AMP by noradrenaline, isoproterenol and forskolin in slices of the cerebral cortex of the rat. In preparations of membranes from similarly treated animals, GppNHp- and forskolin-stimulated aden...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(87)90258-9
更新日期：1987-08-01 00:00:00
abstract：:The so-called generalized polarization (GP) of the fluorescent probe Laurdan and the steady-state fluorescence anisotropy of the probe diphenylhexatriene (DPH) and its phenylpropionic derivative (PA-DPH) were used to study the effects of several organochlorine insecticides of the chlorophenylethane, chlorinated cycloh...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(99)00194-x
更新日期：2000-04-03 00:00:00
abstract：:The rat hemisected spinal cord preparation was used to assess the role of different adrenoceptor subtypes on the modulation of nociceptive reflexes. These were elicited by trains of high intensity electrical stimuli delivered to a lumbar dorsal root. Responses were recorded from the corresponding ventral root in AC- a...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(01)00117-4
更新日期：2001-12-01 00:00:00
abstract：:Effects of cations on binding of 0.1-10 nM 3H-ADTN to calf caudate membranes included decreased apparent Bmax by [Na+] greater than or equal to 100 mM, little effect on Kd or on affinity of other dopamine (DA) agonists (DA and apomorphine), decreased slopes of inhibition curves produced by agonists, but increased affi...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(87)90159-6
更新日期：1987-06-01 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：:N-methyl-D-aspartate (NMDA) receptors play several essential roles in the physiology and pathophysiology of the brain. Their activation results in long-term changes in glutamatergic synaptic transmission in several brain areas, but excessive activation of these receptors induces neurotoxicity. Some of NMDA-mediated ac...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2006.03.025
更新日期：2006-08-01 00:00:00
abstract：:Central administration of corticotropin-like peptides generally blocks the analgesic action of opiate ligands, yet it is unclear whether this is due to an independent hyperalgesic action of corticotropin or to some other mechanism. Single cells in the ventromedial medulla of the anaesthetized rat were characterized as...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(87)90130-4
更新日期：1987-12-01 00:00:00
abstract：:The surface expression and metabolic turnover time of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors are important factors in determining the involvement of these proteins in synaptic function. We used the membrane-impermeant chemical crosslinking reagent BS3 and subsequent immunoblot analysis t...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(98)00135-x
更新日期：1998-10-01 00:00:00
abstract：:The active principle of marijuana, Delta9-tetrahydrocannabinol (Delta9-THC), exerts its pharmacological effects by binding to selective receptors present on the membranes of neurons and other cells. These cannabinoid receptors are normally engaged by a family of lipid mediators, called endocannabinoids, which are thou...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2004.07.018
更新日期：2004-01-01 00:00:00
