Abstract:
:Organophosphates (OPs) pose a constant threat to human health due to their widespread use as pesticides and their potential employment in military and terrorist attacks. The acute toxicity of OPs has been extensively studied; however, the consequences of prolonged or repeated exposure to levels of OPs that produce no overt signs of acute toxicity (i.e. subthreshold levels) are poorly understood. Further, there is clinical evidence that such repeated exposures to OPs lead to prolonged deficits in cognition, although the mechanism for this effect is unknown. In this study, the behavioral and neurochemical effects of repeated, intermittent, and subthreshold exposures to the alkyl OP, diisopropylfluorophosphate (DFP) were investigated. Rats were injected with DFP s.c. (dose range, 0.25-1.0 mg/kg) every other day over the course of 30 days, and then given a 2 week, DFP-free washout period. In behavioral experiments conducted at various times during the washout period, dose dependent decrements in a water maze hidden platform task and a spontaneous novel object recognition (NOR) procedure were observed, while prepulse inhibition of the acoustic startle response was unaffected. There were modest decreases in open field locomotor activity and grip strength (particularly during the DFP exposure period); however, rotarod performance and water maze swim speeds were not affected. After washout, DFP concentrations were minimal in plasma and brain, however, cholinesterase inhibition was still detectable in the brain. Moreover, the 1.0 mg/kg dose of DFP was associated with (brain region-dependent) alterations in nerve growth factor-related proteins and cholinergic markers. The results of this prospective animal study thus provide evidence to support two novel hypotheses: (1) that intermittent, subthreshold exposures to alkyl OPs can lead to protracted deficits in specific domains of cognition and (2) that such cognitive deficits may be related to persistent functional changes in brain neurotrophin and cholinergic pathways.
journal_name
Neurosciencejournal_title
Neuroscienceauthors
Terry AV Jr,Buccafusco JJ,Gearhart DA,Beck WD,Middlemore-Risher ML,Truan JN,Schwarz GM,Xu M,Bartlett MG,Kutiyanawala A,Pillai Adoi
10.1016/j.neuroscience.2010.12.031subject
Has Abstractpub_date
2011-03-10 00:00:00pages
237-53eissn
0306-4522issn
1873-7544pii
S0306-4522(10)01636-2journal_volume
176pub_type
杂志文章相关文献
NEUROSCIENCE文献大全abstract::Phenylethylidenehydrazine (PEH), an analog of the monoamine oxidase inhibitor, beta-phenylethylhydrazine (phenelzine), inhibits the gamma-aminobutyric acid (GABA) catabolic enzyme GABA-transaminase and increases brain levels of GABA. GABA is the predominant fast inhibitory transmitter counteracting glutamatergic excit...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2004.03.007
更新日期:2004-01-01 00:00:00
abstract::Intrauterine growth restriction (IUGR) associates with increased preference for palatable foods and altered insulin sensitivity. Insulin modulates the central dopaminergic response and changes behavioral responses to reward. We measured the release of dopamine in the accumbens during palatable food intake in IUGR rats...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2018.12.036
更新日期:2019-02-21 00:00:00
abstract::The intense immunohistochemical reaction for the enzyme adenosine deaminase displayed by neurons in the tuberomammillary nucleus in the rat was used to study the distribution and morphology of cells comprising this nucleus, their fiber fields within the posterior hypothalamus and their projection pathways from the hyp...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(87)90077-7
更新日期:1987-11-01 00:00:00
abstract::To investigate whether the ageing process might affect neuron-target interactions which influence the phenotype of septal cholinergic neurons, we compared the response of these neurons to partial loss of target tissue in young adult and aged animals. Groups of young adult (four to six months) or aged (24-33 months) ma...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(96)00240-0
更新日期:1996-11-01 00:00:00
abstract::Properties of excitatory synaptic responses in fast-spiking interneurons (FSIs) and pyramidal neurons (PNs) are different; however, the mechanisms and determinants of this diversity have not been fully investigated. In the present study, voltage-clamp recording of miniature excitatory post-synaptic currents (mEPSCs) w...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2015.06.034
更新日期:2015-08-20 00:00:00
abstract::Neuroinflammatory processes associated with induction of cyclooxygenase (COX) have been implicated in the deleterious events resulting in neurodegeneration. The present study was designed to investigate the impact of acute methamphetamine (MA) administration on COX expression and prostaglandin E2 (PGE(2)) production, ...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2007.09.059
更新日期:2007-12-19 00:00:00
abstract::Cerebral glucose hypometabolism is common in temporal lobe epilepsy (TLE). The temporospatial evolution of these metabolic changes during epileptogenesis remains to be determined. We measured the regional normalized cerebral metabolic rate for glucose (nCMRglc) with (18)F-fluorodeoxyglucose (FDG)-small animal positron...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2009.05.041
更新日期:2009-09-15 00:00:00
abstract::Hydrogen peroxide (H2O2) is one of the reactive oxygen species (ROS), endogenously produced during metabolism, which acts as a second messenger. In skeletal muscles, hypoxia- or hyperthermia-induced increase in H2O2 might affect synaptic transmission by targeting the most redox-sensitive presynaptic compartment (Ginia...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2018.12.027
更新日期:2019-02-10 00:00:00
abstract::Previous studies from our laboratory and others have shown that there are major age-related differences in brainstem neuronal function. Since GABAA receptors are major targets for GABA-mediated inhibitory modulation and play a key role in regulating cardiorespiratory function, especially during O2 deprivation, we exam...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(92)90373-a
更新日期:1992-08-01 00:00:00
abstract::The hyperpolarization-activated h channel current (Ih) reported to be present in acutely isolated rat dorsal root ganglion (DRG) neurons is inhibited by Cs+ and ZD7288. It was recently reported that lead (Pb2+) inhibits voltage-gated Ca2+ and K+ channels in DRG neurons but the effect of Pb2+ on Ih has so far not been ...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(03)00279-3
更新日期:2003-01-01 00:00:00
abstract::To examine changes in corticostriatal synaptic transmission in rats with ethanol withdrawal syndrome, intracellular and extracellular responses to subcortical white matter stimulation were recorded in neostriatal slice preparations. The resting membrane potential, input resistance and depolarizing postsynaptic potenti...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(98)00611-3
更新日期:1999-01-01 00:00:00
abstract::Exposure to loud, prolonged sounds (acoustic trauma, AT) leads to the death of both inner and outer hair cells (IHCs and OHCs), death of neurons of the spiral ganglion and degeneration of the auditory nerve. The auditory nerve (8cn) projects to the three subdivisions of the cochlear nuclei (CN), the dorsal cochlear nu...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2015.07.004
更新日期:2015-09-10 00:00:00
abstract::Cocaine- and amphetamine-regulated transcript (CART) and nesfatin-1/nucleobindin 2 (NUCB2) are assumed to play a role in feeding and adaptation to stress. Both peptides are highly expressed in the midbrain non-preganglionic Edinger-Westphal nucleus (npEW), a center implicated in the regulation of stress adaptation and...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2010.07.001
更新日期:2010-10-13 00:00:00
abstract::Purkinje cell maturation during thyroxine-induced metamorphosis in premetamorphic bullfrog tadpoles was studied using electron microscopy and Golgi (silver-impregnated) preparations. Cerebella from tadpoles were examined following 1, 2, or 3 weeks of thyroxine treatment. Particular attention was paid to possible diffe...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(84)90219-7
更新日期:1984-01-01 00:00:00
abstract::A lesion of the entorhinal cortex produces a loss of more than 80% of the synapses in the outer molecular layer of the hippocampus in the rat. However, this synaptic loss is transient. Beginning a few days after denervation, new synapses are formed, virtually replacing the lost inputs within two months. Synaptic remod...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(94)90434-0
更新日期:1994-08-01 00:00:00
abstract::Differential vulnerability in the hindbrain neurons was examined immunohistochemically during hindbrain ischemia in the gerbil. Hindbrain ischemia was produced by extracranial occlusion of the bilateral vertebral arteries just before their entry into the transverse foramen of the cervical vertebra. Local cerebral bloo...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(93)90343-e
更新日期:1993-09-01 00:00:00
abstract::To date, the neurochemical basis underlying the motor and cognitive deficits described in patients with multiple sclerosis (MS) is unclear. Since the neuropeptide somatostatin (SRIF) and the striatum have been implicated in movement control and implicit memory, the aim of this study was to analyze the striatal somatos...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2007.04.065
更新日期:2007-08-10 00:00:00
abstract::Turning in circles is among the behaviors elicited by unilateral cholinergic stimulation of the substantia nigra. Recent studies have shown that microinjection of cholinergic agonists into the substantia nigra pars compacta increases dopamine release and turnover in the striatum of anesthetized rats [Hernández-López e...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(94)90378-6
更新日期:1994-09-01 00:00:00
abstract::The present study set out to assess the possible role of the medial prefrontal cortex (mPFC) cannabinoid CB1 receptors and BDNF/cFOS signaling pathways in morphine-dextromethorphan (DXM) cross state-dependent memory (SDM) using male Wistar rats. Changes on the levels of BDNF and cFOS proteins in the PFC were examined ...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2018.10.012
更新日期:2018-11-21 00:00:00
abstract::Humans perform object recognition effortlessly and accurately. However, it is unknown how the visual system copes with variations in objects' appearance and the environmental conditions. Previous studies have suggested that affine variations such as size and position are compensated for in the feed-forward sweep of vi...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2017.02.050
更新日期:2017-05-04 00:00:00
abstract::PSD-95/SAP90, a molecular scaffold protein, attaches the N-methyl-D-aspartate receptor to cellular signaling pathways through PSD-95/DLG/Z0-1 domain interactions at neuronal synapses.(5,9) This suggests that PSD-95/SAP90 might be involved in many physiological and pathophysiological actions triggered via the N-methyl-...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(00)00193-7
更新日期:2000-01-01 00:00:00
abstract:UNLABELLED:GABA is an important inhibitory transmitter in the CNS. In the enteric nervous system, however, both excitatory and inhibitory actions have been reported. Here, we investigated the effects of GABA on the intracellular Ca2+ concentration of guinea-pig myenteric neurons (at 35 degrees C) using Fura-2-AM. Neuro...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2005.12.023
更新日期:2006-05-12 00:00:00
abstract::There is substantial evidence that prenatal exposure to adverse environmental conditions might lead to the psychiatric disorders that can appear in adolescence or in adulthood; vulnerability to drug addiction may increase as well. It is currently accepted that the alteration of catecholamine transmission in the prefro...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2010.03.046
更新日期:2010-06-16 00:00:00
abstract::We have re-examined in the rat the nuclear localization of the medullary catecholamine-containing cell groups (A1 and A2) and their relation to the vagal motor nuclei using a double labeling method. The vagal nuclei were defined by the retrograde transport of horseradish peroxidase applied to the cervical vagus, and n...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(82)90258-5
更新日期:1982-06-01 00:00:00
abstract::Transthyretin is the major thyroxine-binding protein in the plasma of rodents, and the main thyroxine-binding protein in the cerebrospinal fluid of both rodents and humans. The choroid plexus synthesizes transthyretin and secretes it to the cerebrospinal fluid. Although it was suggested that transthyretin might play a...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(02)00228-2
更新日期:2002-01-01 00:00:00
abstract::The neurotensin/neuromedin N precursor molecule possesses four lysine-arginine dibasic residues which represent potential sites of cleavage by proteolytic maturation enzymes. As shown in the preceding paper, all of these dibasic residues are cleaved to a variable extent in rat brain. The aim of the present study was t...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(94)90212-7
更新日期:1994-05-01 00:00:00
abstract::Walking onto a stationary sled previously experienced as moving induces locomotor aftereffects (LAE, or "broken escalator phenomenon"). This particular form of aftereffect can develop after a single adaptation trial and occurs despite subjects being fully aware that the sled will not move. Here, we investigate whether...
journal_title:Neuroscience
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.neuroscience.2010.06.079
更新日期:2010-09-29 00:00:00
abstract::Mental function has as its cerebral basis a specific dynamic structure. In particular, cortical and limbic areas involved in "higher brain functions" such as learning, memory, perception, self-awareness and consciousness continuously need to be self-adjusted even after development is completed. By this lifelong self-o...
journal_title:Neuroscience
pub_type: 杂志文章,评审
doi:10.1016/s0306-4522(00)00516-9
更新日期:2001-01-01 00:00:00
abstract::Nerve injuries cause pain, paralysis and numbness that can lead to major disability, and newborns often sustain nerve injuries during delivery that result in lifelong impairment. Without a pharmacologic agent to enhance functional recovery from these injuries, clinicians rely solely on surgery and rehabilitation to tr...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2014.10.005
更新日期:2015-01-22 00:00:00
abstract::We reported previously that sensory neurons isolated from mice with a heterozygous mutation of the Nf1 gene (Nf1+/-) exhibited greater excitability and increased sodium current densities compared with wildtype mice. This raises the question as to whether the increased current density resulted from post-translational m...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2011.12.045
更新日期:2012-03-29 00:00:00