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1.
Mar Pollut Bull ; 159: 111481, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32768672

ABSTRACT

The region around the Gulf is moving toward a nuclear energy option with the first nuclear power plant now operational in Bushehr, Iran. Others are soon to be commissioned in Abu Dhabi and in Saudi Arabia. For this reason, radiological safety is becoming a prime concern in the region. This review compiles published data on radionuclide concentrations in seawater, sediment, and biota that have been analyzed in the Gulf countries, along with spatial distribution patterns to enable a synoptic view of the available datasets. The seawater concentrations of 3H, 210Po, 210Pb, 137Cs, and 90Sr varied between 130 and 146, 0.48-0.68, 0.75-0.89, 1.25-1.38, 0.57-0.78 mBq L-1, respectively. The 226Ra concentration in seawater varied between 0.26 and 3.82 Bq L-1. Extremely high 40K concentrations between 132 and 149 Bq L-1 have been reported from the Iranian coast compared to 8.9-9.3 Bq L-1 from the western side of the Gulf. Concentrations of 40K, total 210Pb, 137Cs, 90Sr, 226Ra, 228Ra, 238U, 235U, 234U, 239+240Pu, and 238Pu were determined in sediment and ranged between 353 and 445, 23.6-44.3, 1.0-3.1, 4.8-5.29, 17.3-20.5, 15-16.4, 28.7-31.4, 1.26-1.30, 29.7-30.0, 0.045-0.21 and 0.028-0.03 Bq kg-1 dry weight, respectively. Significantly higher 137Cs values have been reported from the Iranian coast compared to the western coast of the Gulf. Whole fish concentrations of 40K, 226Ra, 224Ra, 228Ra, 137Cs, 210Po and 90Sr ranged between 230 and 447, 0.7-7.3, <0.5-6.6, <0.5-15.80, <0.17, 0.88-4.26 and 1.86-5.34 Bq kg-1 dry weight, respectively. 210Po was found to be highly concentrated in several marine organisms with the highest 210Po concentration found in the clam Marcia marmorata (193.5-215.6 Bq kg-1 dry weight). The review highlights the overall paucity of data and inconsistencies in the measurement of radionuclides throughout the Gulf region. Further, since the region is moving toward nuclear energy to meet its increasing energy demand, and coupled with the environmental effects from offshore oil exploration and the heavy impact of climate change, there is a pressing need to undertake a comprehensive marine radioactivity monitoring and assessment effort by conducting a joint cruise in the Gulf with participation of all the adjoining countries. Several recommendations on sampling marine matrixes in the Gulf are given with the aim of improving comparability of radionuclide data from the various studies undertaken in the Gulf region.


Subject(s)
Radiation Monitoring , Radioactivity , Water Pollutants, Radioactive/analysis , Animals , Iran , Saudi Arabia , Seawater , United Arab Emirates
2.
J Environ Radioact ; 222: 106323, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32554167

ABSTRACT

210Po, being a highly radiotoxic isotope, could contribute to significant inhalation dose to humans. This study establishes the first set of atmospheric 210Po data in aerosol samples collected across Kuwait. The primary focus of this study is to investigate spatio-temporal variability of atmospheric 210Po and assess its sources, including anthropogenic contributions. Measurements of 210Po in aerosols collected over a period of 23 months (January 2018-November 2019) from three different locations, i.e., a remote area (120 km) north of Kuwait City, Kuwait city and an industrial site (60 km from Kuwait City center). Specific activities of 210Po were determined in 3 different size fractions (0.39-2.5 µm, 2.5-10 µm and ≥10 µm) and the highest activity was observed in the fine fraction (PM0.39- 2.5) across all sampling stations during both the summer and winter seasons. The highest activities in all the size fractions were measured downwind of the Industrial site that houses oil refineries, cement factory and some other industries including a Power and Desalination Plant. In terms of temporal variations, higher summertime activities were observed across the spatial domain. Longer residence time of atmospheric 222Rn-produced 210Pb resulting in lower scavenging of atmospheric 210Pb, due to very little precipitation in summer, will result in higher atmospheric 210Po.


Subject(s)
Air Pollutants , Polonium , Radiation Monitoring , Aerosols , Cities , Environmental Monitoring , Humans , Kuwait , Particle Size , Polonium/analysis , Seasons
3.
J Environ Radioact ; 205-206: 1-6, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31078971

ABSTRACT

An experimental study was conducted to assess loss of 210Po due to cooking fresh seafood, and provide a more realistic and reliable dose estimate that humans may receive from consuming cooked seafood. Fresh fish and shrimp samples from Northern Gulf waters were grilled and boiled to simulate the effect of different cooking methods. Sixteen different species of fish were compared and significant differences in 210Po concentration in uncooked samples were observed between species (ANOVA I, F15,79 = 362.81, p < 0.0001). The effect of the treatment (uncooked, grilled, boiled and stock) was compared for each species and it was found that cooking led to a significant decrease in 210Po concentration ranging from 14 to 58% compared to the uncooked samples, with no difference between grilled or boiled treatments. The effect of the cooking and shrimp treatment on 210Po concentration was tested using ANOVA II after logarithmic transformation. Cooking led to a significant 38% reduction of 210Po concentration as compared to uncooked treatments with no difference between grilled and boiled samples (ANOVA I: F3,99 = 14.72, p < 0.0001). The two treatments with deveined shrimp led to a 75% decrease in 210Po concentration as compared to all other treatments. As a consequence, cooked deveined shrimp contained an 84% lower 210Po concentration than whole uncooked shrimp. As 210Po is known to be the major contributor to radiation dose in humans consuming seafood, based on the results obtained, it is evident there is a need to re-examine how committed effective doses (CEDs) are best calculated for seafood consuming populations considering that most populations consume fish and shellfish cooked.


Subject(s)
Cooking , Polonium/analysis , Radiation Dosage , Radiation Monitoring , Seafood/analysis , Animals , Decapoda/chemistry , Fishes , Humans , Kuwait , Shellfish/analysis
4.
Article in English | MEDLINE | ID: mdl-30704142

ABSTRACT

Polyolefin (PO) polymers constitute the majority of consumer plastic commodities. The reliance on such materials make it near imposable to avoid touching one in any given day. Therefore, the accumulation of plastic solid waste (PSW) in developed and developing societies alike requires immediate attention to manage and valorize this type of waste. In this work, PSW originating from real life sources and virgin linear low-density polyethylene (LLDPE) films were compounded in a mechanical recycling effort. The recycled blends constituted up to 100% (by weight) of the waste material. Accelerated weathering (aging) was conducted on the blends, reaching threshold limit of exposure to study the major changes occurring on the recycled blends. Thermogravimetry and differential scanning calorimetry (DSC) were used to determine their characteristics and applicability for future recycling using thermo-chemical treatment (TCT) methods. Analytical solution methods following the international committee of thermal analysis and calorimetry (ICTAC) were followed in conducting the measurements and kinetic calculations alike. A novel analytical mathematical solution model is also introduced to determine both the pre-exponential factor (Ao) and apparent activation energy (Ea) of the degradation reaction. The model proved to be a more accurate analysis tool, and the work in whole enabled the determination of future plans for using such waste components as a feedstock to thermal units.


Subject(s)
Plastics/chemistry , Polyenes/chemistry , Solid Waste , Calorimetry, Differential Scanning , Kinetics , Recycling/methods , Weather
5.
Mar Pollut Bull ; 129(1): 343-346, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29680557

ABSTRACT

Marine phytoplankton is a primary producer in the ocean that forms the base of the marine food web and supports the pelagic food chain. The two dominant groups of phytoplankton observed in northern Gulf waters are diatoms and dinoflagellates. The diatoms outnumber dinoflagellates in the Gulf waters. This study presents baseline information on the concentration of 210Po among selected phytoplankton in the northern Gulf. The concentration among diatoms varies between 6.99 and 11.4 Bq kg-1 wwt, whereas a higher concentration range of 8.51-15.41 Bq kg-1 wwt was observed among dinoflagellates. The diatoms analyzed includes Thalassiosira spp. - 10.2-11.4 Bq kg-1 wwt; Chaetoceros spp. - 6.99-7.14 Bq kg-1 wwt; Rhizosolenia spp. - 9.12-9.95 Bq kg-1 wwt. The analyzed dinoflagellate genera include Gymnodinium spp. - 8.51-8.78 Bq kg-1 wwt; Noctiluca spp. - 15.2-15.4 Bq kg-1 wwt; and Karenia spp. - 14.1-14.9 Bq kg-1 wwt. The 210Po concentration in seawater shows a seasonal variation, with a higher concentration range of 0.70 and 0.58 mBq L-1 during summer and autumn, whereas a lower range in concentration of 0.38 and 0.30 mBq L-1 occurring during winter and spring. The resultant computed concentration factors vary between 2 ∗ 104-5 ∗ 104 demonstrating a significant 210Po enrichment in the base of the pelagic food chain.


Subject(s)
Diatoms/chemistry , Dinoflagellida/chemistry , Polonium/analysis , Radiation Monitoring/methods , Seawater/chemistry , Water Pollutants, Radioactive/analysis , Food Chain , Kuwait , Seasons
6.
Mar Pollut Bull ; 120(1-2): 396-400, 2017 Jul 15.
Article in English | MEDLINE | ID: mdl-28487058

ABSTRACT

The Arabian Gulf is a semi-enclosed water body that has witnessed accelerated anthropogenic activity, in terms of commissioning of nuclear power plants, desalination facilities, oil refineries and extensive coastal development. Furthermore, three wars during the past three decades is a potential worry. This study presents the first plutonium baseline in seawater from the Northern Arabian Gulf. The 239+240Pu concentrations in seawater vary, between 2.9 and 4.9mBqm-3, a range that is comparable to other water masses at this latitude. The 238Pu ranged between 0.04 and 0.05mBqm-3 and the 137Cs concentration between 1.04 and 1.18Bqm-3. The ratio of 238Pu/239+240Pu at all eight sampling stations was 0.01, while the ratio of 239+240Pu/137Cs varied between 0.01 and 0.02. The presence of 137Cs and 239+240Pu in seawater from this region can mainly be attributed to the global atmospheric deposition and fluvial transport. The seawater concentration of 239+240Pu is five order of magnitude lower than bottom sediments in the area.


Subject(s)
Cesium/analysis , Plutonium/analysis , Water Pollutants, Radioactive/analysis , Cesium Radioisotopes , Geologic Sediments , Middle East , Seawater
7.
J Environ Radioact ; 174: 23-29, 2017 Aug.
Article in English | MEDLINE | ID: mdl-27670204

ABSTRACT

The tendency of 210Po to concentrate in body tissue poses a serious concern of radiological safety. This study compiles available information and presents recent 210Po data for the marine food web in the northern Gulf waters. Since 210Po is concentrated in marine biota, a large number of samples of various marine organisms covering several trophic levels, from microalgae to sharks, were analyzed. 210Po was found to be highly concentrated in several marine species with the highest 210Po concentrations found in yellowfin tuna, i.e. 37.3-44.9, 451-548, and 1511-1693 Bq kg-1 wwt in muscle, digestive system and liver, respectively. In most dissected fish samples, 210Po showed increasing concentrations in the following order: edible tissue, gills, digestive system, liver and fecal matter. Fish feces had 210Po concentrations several orders of magnitude higher than that in seawater, fish muscle, and the fishes' ingested food. The high 210Po concentration in fish fecal matter suggests that the bulk of 210Po content in fish is eventually excreted back into the environment as fecal pellets. In most fish high concentrations were noted in liver, with the highest 210Po concentration recorded in yellowfin tuna liver. Moreover, 210Po concentration in the soft tissue of tunicate and bryozoan samples were 872-1012 and 402-527 Bq kg-1 wwt, respectively, far higher than that in fish muscle (0.04-44.9 Bq kg-1 wwt). It was observed that the maximum 210Po concentration in edible fish tissue among the fish in trophic level 2 was an order of magnitude lower than those in trophic level 3 and two orders of magnitude lower compared to fish in trophic level 4. The highest concentrations in the muscle tissue were observed in the following order: tunicate > bryozoan > mollusc > crustacean > algae > fish. Among all the biota analyzed, the highest overall concentration of 210Po was noted in yellowfin tuna (Thunnus albacores) indicating a potential biomagnification of 210Po in this particular top predator species. In general, 210Po concentrations found in the commercially important fish from Kuwaiti waters were comparable to levels that have been reported for similar fish species from several other marine areas worldwide.


Subject(s)
Food Chain , Polonium/metabolism , Radiation Monitoring , Water Pollutants, Radioactive/metabolism , Animals , Fishes , Indian Ocean , Mollusca , Polonium/analysis , Seawater , Sharks , Water Pollutants, Radioactive/analysis
8.
Mar Pollut Bull ; 100(2): 651-61, 2015 Nov 30.
Article in English | MEDLINE | ID: mdl-26490408

ABSTRACT

The Arabian Gulf region is moving towards a nuclear energy option with the first nuclear power plant now operational in Bushehr, Iran, and others soon to be constructed in Abu Dhabi and Saudi Arabia. Radiological safety is becoming a prime concern in the region. This study compiles available data and presents recent radionuclide data for the northern Gulf waters, considered as pre-nuclear which will be a valuable dataset for future monitoring work in this region. Radionuclide monitoring in the marine environment is a matter of prime concern for Kuwait, and an assessment of the potential impact of radionuclides requires the establishment and regular updating of baseline levels of artificial and natural radionuclides in various environmental compartments. Here we present baseline measurements for (210)Po, (210)Pb, (137)Cs, (90)Sr, and (3)H in Kuwait waters. The seawater concentration of (3)H, (210)Po, (210)Pb, (137)Cs, and (90)Sr vary between 130-146, 0.48-0.68, 0.75-0.89, 1.25-1.38 and 0.57-0.78 mBq L(-1), respectively. The (40)K concentration in seawater varies between 8.9-9.3 Bq L(-1). The concentration of (40)K, total (210)Pb, (137)Cs, (90)Sr, (226)Ra, (228)Ra, (238)U, (235)U, (234)U, (239+240)Pu and (238)Pu were determined in sediments and range, respectively, between 353-445, 23.6-44.3, 1.0-3.1, 4.8-5.29, 17.3-20.5, 15-16.4, 28.7-31.4, 1.26-1.30, 29.7-30.0, 0.045-0.21 and 0.028-0.03 Bq kg(-1) dry weight. Since, radionuclides are concentrated in marine biota, a large number of marine biota samples covering several trophic levels, from microalgae to sharks, were analyzed. The whole fish concentration of (40)K, (226)Ra, (224)Ra, (228)Ra, (137)Cs, (210)Po and (90)Sr range between 230-447, 0.7-7.3, <0.5-6.6, <0.5-15.80, <0.17, 0.88-4.26 and 1.86-5.34 Bq kg(-1) dry weight, respectively. (210)Po was found to be highly concentrated in several marine organisms with the highest (210)Po concentration found in Marica marmorata (193.5-215.6 Bq kg(-1) dry weight). (210)Po in most dissected fish samples shows increasing concentrations in the following order: edible tissue, gills, digestive system, liver and fecal matter. Fish fecal pellets had (210)Po concentrations several orders of magnitude higher than the seawater, fish muscle, and the fishes' ingested food. The high (210)Po concentration in fish fecal matter, suggest that the bulk of (210)Po content in fish was eventually excreted back into the environment as fecal pellets. In most fish high concentrations were noted in liver, with the highest (210)Po concentration recorded in shark liver (126.2-141.5 Bq kg(-1) wet). Moreover, (210)Po concentration in the soft tissue of molluscs (10.36-215.60 Bq kg(-1) dry weight) was far higher than that in fish muscle (0.05-7.49 Bq kg(-1) wet weight). A seasonal drop in (210)Po concentration in seawater was observed to vary with the abundance of phytoplankton and macroalgae due possibly to biological dilution. (137)Cs concentration in all the fish sampled was below the detection limit, and the concentration in seawater was also low; hence such low levels provide an opportunity to use this radionuclide as an indicator for any future radiocesium releases in this region.


Subject(s)
Fishes , Phytoplankton/chemistry , Water Pollutants, Radioactive/analysis , Animals , Cesium Radioisotopes/analysis , Food Contamination, Radioactive/analysis , Kuwait , Lead Radioisotopes/analysis , Mollusca/metabolism , Polonium/analysis , Polonium/pharmacokinetics , Seafood/analysis , Seasons , Seawater , Sharks/metabolism , Strontium Radioisotopes/analysis , Tissue Distribution , Water Pollutants, Radioactive/pharmacokinetics
9.
Mar Pollut Bull ; 64(11): 2599-602, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22863352

ABSTRACT

This baseline study highlights the (210)Po variation in whole fishes with different feeding habits. Whole-body (210)Po concentrations were determined in ten important commercial fish species found in the northern Arabian Gulf to serve as baseline data. Primarily, (210)Po is absorbed from water, concentrated by phytoplankton and microzooplankton, and then transferred to the next trophic level along the marine food chain. The lowest concentration of (210)Po was measured in larger carnivorous fishes like hamoor (0.089 Bq kg(-1)), while the highest was found in the fishes that feed on algae, zooplanktons and detritus, like battan (3.30 Bq kg(-1)). The baseline data can be used to understand both the trophic transfer of (210)Po in the marine food chain and the (210)Po concentration factors in fish from the Arabian Gulf.


Subject(s)
Fishes/metabolism , Polonium/metabolism , Radiation Monitoring , Water Pollutants, Radioactive/metabolism , Animals , Food Chain , Kuwait , Phytoplankton/metabolism , Risk Assessment , Seafood/statistics & numerical data , Zooplankton/metabolism
10.
Neurobiol Dis ; 39(1): 105-15, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20307668

ABSTRACT

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is efficacious in treating the motor symptoms of Parkinson's disease (PD). However, the impact of STN-DBS on the progression of PD is unknown. Previous preclinical studies have demonstrated that STN-DBS can attenuate the degeneration of a relatively intact nigrostriatal system from dopamine (DA)-depleting neurotoxins. The present study examined whether STN-DBS can provide neuroprotection in the face of prior significant nigral DA neuron loss similar to PD patients at the time of diagnosis. STN-DBS between 2 and 4 weeks after intrastriatal 6-hydroxydopamine (6-OHDA) provided significant sparing of DA neurons in the SN of rats. This effect was not due to inadvertent lesioning of the STN and was dependent upon proper electrode placement. Since STN-DBS appears to have significant neuroprotective properties, initiation of STN-DBS earlier in the course of PD may provide added neuroprotective benefits in addition to its ability to provide symptomatic relief.


Subject(s)
Cytoprotection/physiology , Deep Brain Stimulation/methods , Dopamine/biosynthesis , Nerve Degeneration/metabolism , Nerve Degeneration/prevention & control , Parkinsonian Disorders/therapy , Substantia Nigra/pathology , Subthalamic Nucleus/physiology , Animals , Cell Death/physiology , Disease Models, Animal , Male , Nerve Degeneration/pathology , Neural Inhibition/physiology , Parkinsonian Disorders/pathology , Rats , Rats, Sprague-Dawley , Substantia Nigra/metabolism , Subthalamic Nucleus/metabolism , Subthalamic Nucleus/pathology , Treatment Outcome
11.
Neuroscience ; 114(4): 935-43, 2002.
Article in English | MEDLINE | ID: mdl-12379249

ABSTRACT

The midbrain periaqueductal gray contains both neurotensin type-1 and type-2 receptors. Behavioral studies have shown that the analgesic effect of neurotensin is mediated through its interaction with the type-2 receptors. These receptors specifically bind the type-1 histamine antagonist, levocabastine. Recently, it has been shown that another histamine-1 antagonist, diphenhydramine, blocks the analgesic effect of neurotensin. In addition, it has been shown that a non-peptide neurotensin antagonist, SR142948A, binds to both types of neurotensin receptors and blocks the analgesic effect of exogenously applied neurotensin. Major afferents to the periaqueductal gray arise from the medial preoptic nucleus of the hypothalamus. This region contains neurotensinergic neurons, and the expression of neurotensin mRNA in this region increases following cold-water swim stress that leads to opioid-independent analgesia. The goal of this study was to determine whether the responses of periaqueductal gray neurons to stimulation of the medial preoptic nucleus are modified by local injection of diphenhydramine and SR142948A. Because the cellular basis of the effects of diphenhydramine on periaqueductal gray neurons had not been reported, we also examined the effects of diphenhydramine on the baseline-firing rate and synaptic transmission using in vivo and in vitro methods. The results of the in vitro studies indicate that diphenhydramine concentrations above 500 nM significantly reduce the baseline firing of the periaqueductal gray neurons without a significant effect on the frequency of postsynaptic potentials. At concentrations below 100 nM, diphenhydramine has little effect on the baseline-firing rate but partially blocks the response to neurotensin. The results of the in vivo studies showed similar effects of diphenhydramine. At high concentrations it inhibited periaqueductal gray neurons, but at low concentrations it had no effect on the baseline-firing rate and it blocked the response to neurotensin and to medial preoptic nucleus stimulation. Unlike diphenhydramine, SR142948A had virtually no effect on the baseline-firing rate but blocked the response to neurotensin and to stimulation of the medial preoptic nucleus. It is concluded that: (1) SR142948A, at a dose that completely blocks the effect of exogenously applied neurotensin on periaqueductal gray neurons, has little effect on their baseline-firing rates. (2) Because of its effect on the baseline-firing rate, only low doses of diphenhydramine can be used as an antagonist of the neurotensin analgesic effect. (3) Responses of periaqueductal gray neurons to medial preoptic nucleus stimulation is, in part, mediated by a neurotensinergic network within the periaqueductal gray.


Subject(s)
Adamantane/analogs & derivatives , Adamantane/pharmacology , Anesthetics, Local/pharmacology , Diphenhydramine/pharmacology , Imidazoles/pharmacology , Neurons/drug effects , Periaqueductal Gray/cytology , Preoptic Area/cytology , Animals , Electrophysiology , Male , Membrane Potentials/drug effects , Neural Pathways/drug effects , Neurons/physiology , Rats , Rats, Sprague-Dawley , Stimulation, Chemical
12.
Med Clin North Am ; 85(4): 911-41, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11480265

ABSTRACT

The typical migraine patient is exposed to a myriad of migraine triggers on a daily basis. These triggers potentially can act at various sites within the cerebral vasculature and the central nervous system to promote the development of migraine headache. The challenge to the physician is in the identification and avoidance of migraine trigger factors within patients suffering from migraine headache. Only through a rational approach to migraine trigger factors can physicians develop an appropriate treatment strategy for migraine patients.


Subject(s)
Migraine Disorders/etiology , Diagnosis, Differential , Humans , Migraine Disorders/prevention & control , Patient Care Team , Risk Factors
13.
Brain Res Mol Brain Res ; 86(1-2): 145-52, 2001 Jan 31.
Article in English | MEDLINE | ID: mdl-11165381

ABSTRACT

Stress-induced analgesia is a well-documented phenomenon that occurs in all mammalian species. Forced cold water swim produces a type of stress-induced analgesia that is independent of mu opioid receptors. The neuropeptide neurotensin (NT) has been implicated in mu opioid-independent analgesia (MOIA), but the circuitry of this system is largely unknown. The medial preoptic area (MPO) and lateral hypothalamus (LH) are two regions that are known to modulate pain processing. These two regions also contain neurotensinergic projections to the periaqueductal gray, a region that has been shown to produce MOIA upon injection of NT. The goal of this study was to determine if cold water swim (CWS) stress, which produces MOIA, activates the NT-ergic systems in these two regions. In situ hybridization results indicate that CWS increases the level of NT mRNA within neurons in the MPO and LH, suggesting that these two regions are activated during this process.


Subject(s)
Cold Temperature , Hypothalamic Area, Lateral/physiology , Neurotensin/genetics , Preoptic Area/physiology , Stress, Physiological/physiopathology , Animals , Gene Expression/physiology , Hot Temperature , In Situ Hybridization , Male , Pain Threshold/physiology , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Swimming/physiology
14.
J Neurochem ; 72(1): 17-28, 1999 Jan.
Article in English | MEDLINE | ID: mdl-9886050

ABSTRACT

Choline acetyltransferase (ChAT) is a specific phenotypic marker of cholinergic neurons. Previous reports showed that different upstream regions of the ChAT gene are necessary for cell type-specific expression of reporter genes in cholinergic cell lines. The identity of the mouse ChAT promoter region controlling the establishment, maintenance, and plasticity of the cholinergic phenotype in vivo is not known. We characterized a promoter region of the mouse ChAT gene in transgenic mice, using beta-galactosidase (LacZ) as a reporter gene. A 3,402-bp segment from the 5'-untranslated region of the mouse ChAT gene (from -3,356 to +46, +1 being the translation initiation site) was sufficient to direct the expression of LacZ to selected neurons of the nervous system; however, it did not provide complete cholinergic specificity. A larger fragment (6,417 bp, from -6,371 to +46) of this region contains the requisite regulatory elements that restrict expression of the LacZ reporter gene only in cholinergic neurons of transgenic mice. This 6.4-kb DNA fragment encompasses 633 bp of the 5'-flanking region of the mouse vesicular acetylcholine transporter (VAChT), the entire open reading frame of the VAChT gene, contained within the first intron of the ChAT gene, and sequences upstream of the start coding sequences of the ChAT gene. This promoter will allow targeting of specific gene products to cholinergic neurons to evaluate the mechanisms of diseases characterized by dysfunction of cholinergic neurons and will be valuable in design strategies to correct those disorders.


Subject(s)
Carrier Proteins/genetics , Choline O-Acetyltransferase/genetics , Cholinergic Fibers/enzymology , Membrane Transport Proteins , Neurons/enzymology , Promoter Regions, Genetic/physiology , Vesicular Transport Proteins , 5' Untranslated Regions/physiology , Animals , Cholinergic Fibers/chemistry , Gene Expression Regulation, Enzymologic , Genes, Reporter , Lac Operon , Mice , Mice, Transgenic , Molecular Sequence Data , Neurons/chemistry , Neurons/ultrastructure , Sciatic Nerve/cytology , Spinal Cord/cytology , Transgenes/physiology , Vesicular Acetylcholine Transport Proteins
15.
Brain Res ; 805(1-2): 69-87, 1998 Sep 14.
Article in English | MEDLINE | ID: mdl-9733923

ABSTRACT

Previous studies have shown that the injection of nitric oxide (NO) donating compounds into the dorsal periaqueductal gray region of the midbrain (PAG) decreases mean arterial pressure (MAP), while the injection of NO synthase (NOS) inhibitors increases MAP. In this study we used both in-vivo and in-vitro preparations and examined the effect of a NO donor and a NOS inhibitor on MAP, membrane properties, and synaptic activities in PAG neurons. We found that: (1) Injection of the NO donor hydroxylamine (HA) into the dorsal PAG decreased MAP, while the injection of the neuronal NOS (nNOS) inhibitor, 1-(2-trifluoromethylphenyl) imidazole (TRIM) increased MAP. These responses were consistent and site-specific. (2) HA-evoked hypotensive responses were mediated by PAG neuronal activity, because they were blocked by pre-injection with gamma-amino-butyric acid (GABA). (3) HA consistently increased the rate of observable synaptic events while TRIM consistently decreased the rate of observable synaptic events. (4) Bicuculline (BIC) and naloxone (NAL) blocked HA-evoked increases in the rate of observable inhibitory synaptic events. (5) Perfusion with sodium nitroprusside (SNP) and illumination with bright light consistently elevated rates of observable synaptic events, and SNP-evoked increases of excitatory synaptic events were blocked by pretreatment with glutamic acid antagonists. (6) PAG-medullary projecting neurons exhibited similar response patterns. The results of this study suggest that: (1) NO production within the PAG is a major component of PAG-mediated cardiovascular responses. (2) The effects of NO may be mediated in part by increased presynaptic vesicular release of glutamic acid, GABA, and enkephalin.


Subject(s)
Enkephalins/physiology , Glutamic Acid/physiology , Nitric Oxide/pharmacology , Periaqueductal Gray/physiology , Synapses/drug effects , gamma-Aminobutyric Acid/physiology , Animals , Bicuculline/pharmacology , Blood Pressure/drug effects , Enzyme Inhibitors/pharmacology , Hydroxylamine/pharmacology , Imidazoles/pharmacology , Male , Membrane Potentials/drug effects , Naloxone/pharmacology , Nerve Net/physiology , Neural Inhibition/drug effects , Neural Inhibition/physiology , Periaqueductal Gray/drug effects , Rats , Rats, Sprague-Dawley , Synapses/physiology
16.
Brain Res ; 765(2): 208-17, 1997 Aug 15.
Article in English | MEDLINE | ID: mdl-9313893

ABSTRACT

Stimulation of the medial preoptic nucleus of the hypothalamus (MPO) has been shown to produce decreases in mean arterial pressure (MAP) by a pathway involving the periaqueductal gray region of the midbrain (PAG). Previous studies have shown that the injection of nitric oxide (NO) donating compounds into the dorsal PAG also decreases MAP, while the injection of nitric oxide synthase (NOS) inhibitors increases MAP. Collectively these studies suggest that the MPO elicited hypotensive response may involve NO production in PAG neurons. In this study, we investigated this hypothesis. We found that: (1) Bilateral injection of the NOS inhibitor 7-nitro indazole (7-NI) into the dorsolateral PAG cell columns produced elevations in MAP in a highly consistent and site specific fashion. (2) Microinjection of 7-NI in quantities that were too low to directly influence MAP blocked the MPO evoked hypotensive response in 9/11 cases. (3) While 41% of dorsal PAG neurons had baseline firing rates that were sensitive to 7-NI, 69% of PAG neuronal responses to MPO stimulation were blocked by 7-NI. (4) Inhibitory responses that were not blocked by 7-NI had significantly shorter latencies to onset in the presence of 7-NI. (5) PAG neurons that projected to the medulla exhibited similar electrophysiologic response patterns. Our results suggest the following: (1) The dorsolateral PAG contains a NO producing hypotensive network. (2) The MPO elicited hypotensive response may utilize this network. (3) Stimulation of the MPO elicits NO dependent responses from PAG neurons, some of which do project to medullary-cardiovascular control centers.


Subject(s)
Hypothalamus/physiology , Mesencephalon/physiology , Neurons/physiology , Nitric Oxide/physiology , Periaqueductal Gray/physiology , Preoptic Area/physiology , Animals , Male , Rats , Rats, Sprague-Dawley
17.
Am J Physiol ; 271(6 Pt 1): C2004-15, 1996 Dec.
Article in English | MEDLINE | ID: mdl-8997203

ABSTRACT

Annexin VI is a member of a Ca(2+)-dependent phospholipid-binding protein family that participates in the transduction of the intracellular Ca2+ signal. We have identified annexin VI as one of the major annexins expressed differentially by sensory neurons of dorsal root ganglia (DRG) and by neurons of spinal cord (SC) of the rat and the mouse. This annexin shows a preferential localization at the plasma membrane of the soma and cellular processes, particularly in motoneurons of the SC. This finding suggests an active role of annexin VI in the Ca(2+)-dependent regulation of plasma membrane functions. To test this possibility, the neuronal function of annexin VI was evaluated by whole cell electrophysiology of mouse embryo SC and DRG neurons. An antibody was developed that has the property of neutralizing annexin VI-phospholipid interactions. The intracellular perfusion of individual neurons in culture, either from SC or DRG, with monospecific affinity-purified anti-annexin VI antibodies resulted in an increase in the magnitude of the K+ current and in an increase in the Ca2+ current in sensory neurons. Our results suggest that the endogenous annexin VI regulates the Ca2+ conductance, which indirectly modifies Ca(2+)-dependent ionic conductances in SC and DRG neurons.


Subject(s)
Annexin A6/metabolism , Calcium/metabolism , Ganglia, Spinal/metabolism , Neurons/metabolism , Potassium/metabolism , Signal Transduction , Spinal Cord/metabolism , Animals , Annexin A6/analysis , Cells, Cultured , Female , Ion Transport , Mice , Pregnancy , Rats , Rats, Sprague-Dawley
18.
Brain Res ; 740(1-2): 141-50, 1996 Nov 18.
Article in English | MEDLINE | ID: mdl-8973808

ABSTRACT

In this study we examined (1) the effect of stimulation of the MPO on the firing activity of neurons in the PAG, (2) the role of glutamic acid in this interaction and, (3) whether reversible blockade of neuronal activity in the PAG by lidocaine can alter the effect of stimulation of the MPO on arterial blood pressure. Single pulse stimulation of the MPO produced a biphasic response in 2/32 cells and inhibited 3/32 cells. Train electrical stimulation excited 21/54 cells and inhibited 12/54 cells. The latencies to the onset of the excitatory and the inhibitory effects were not different, but the duration of the excitatory effect was slightly longer than that of the inhibitory effect. Chemical stimulation of the MPO excited 17/97 cells and inhibited 16/97 cells. The latency to onset of the excitatory response to stimulation of the MPO was longer but the duration was shorter than that of the inhibitory response. In 83% of the animals (29/35), stimulation of the MPO produced a decrease in mean arterial pressure (MAP). The duration of the response was 196.9 +/- 20.9 s and the average decrease in the MAP was 18.2 +/- 1.4 mmHg. Application of KYN blocked the excitatory response to stimulation of the MPO in 8/16 cells and the inhibitory response of 3/10 cells. Injection of lidocaine into the PAG by itself had no effect on the arterial blood pressure. However, in all animals (n = 10) lidocaine totally or significantly reduced the magnitude of the blood pressure change produced by stimulation of the MPO in a reversible manner. These studies electrophysiologically confirm a pathway between the MPO and the PAG that is, in part, under glutamatergic control. In addition, our results demonstrate that stimulation of the MPO produces a distinctive depressor effect that is mediated through the PAG.


Subject(s)
Blood Pressure/physiology , Neural Pathways/physiology , Periaqueductal Gray/physiology , Preoptic Area/physiology , Animals , Electric Stimulation , Male , Rats , Rats, Sprague-Dawley
19.
Neurosci Lett ; 214(1): 5-8, 1996 Aug 16.
Article in English | MEDLINE | ID: mdl-8873118

ABSTRACT

We electrophysiologically examined the connection between the basolateral nucleus of the amygdala (BLA) and the periaqueductal gray (PAG) and examined the role of the central nucleus of the amygdala (CNA) in this pathway. Train electrical stimulation of the BLA excited 21% (7/33) and inhibited 27% (9/33) of the cells recorded in the PAG. Chemical stimulation of the BLA excited 23% (13/56) and inhibited 16% (9/56) of the cells recorded in the PAG. Injection of lidocaine into the CNA by itself had no effect on PAG cells (n = 9) or on blood pressure but blocked the effect of BLA stimulation on PAG neurons in 78% of the cells recorded. It was concluded that: (1) PAG cells respond to BLA stimulation; (2) the majority of these cells are located in the dorsolateral and lateral columns of the PAG; and (3) the CNA modulates a majority of the activities of the BLA in the PAG.


Subject(s)
Amygdala/physiology , Periaqueductal Gray/physiology , Amygdala/cytology , Amygdala/drug effects , Animals , Electric Stimulation , Electrophysiology , Lidocaine/pharmacology , Male , Mesencephalon , Neural Inhibition , Neural Pathways/cytology , Neural Pathways/physiology , Neurons/physiology , Periaqueductal Gray/cytology , Rats , Rats, Sprague-Dawley
20.
J Comp Neurol ; 368(3): 356-70, 1996 May 06.
Article in English | MEDLINE | ID: mdl-8725344

ABSTRACT

The annexins are a family of Ca(2+)-dependent phospholipid-binding proteins. In the present study, the spatial expression patterns of annexins I-VI were evaluated in the rat dorsal root ganglia (DRG) and spinal cord (SC) by using indirect immunofluorescence. Annexin I is expressed in small sensory neurons of the DRG, by most neurons of the SC, and by ependymal cells lining the central canal. Annexin II is expressed by most sensory neurons of the DRG but is primarily expressed in the SC by glial cells. Annexin III is expressed by most sensory neurons, regardless of size, by endothelial cells lining the blood vessels, and by the perineurium. In the SC, annexin III is primarily expressed by astrocytes. In the DRG and the SC, annexin IV is primarily expressed by glial cells and at lower levels by neurons. In the DRG, annexin V is expressed in relatively high concentrations in small sensory neurons in contrast to the SC, where it is expressed mainly by ependymal cells and by small-diameter axons located in the superficial laminae of the dorsal horn areas. Annexin VI is differentially expressed by sensory neurons of the DRG, being more concentrated in small neurons. In the SC, annexin VI has the most striking distribution. It is concentrated subjacent to the plasma membrane of motor neurons and their processes. The differential localization pattern of annexins in cells of the SC and DRG could reflect their individual biological roles in Ca(2+)-signal transduction within the central nervous system.


Subject(s)
Annexins/biosynthesis , Ganglia, Spinal/chemistry , Rats, Sprague-Dawley/physiology , Spinal Cord/chemistry , Animals , Annexin A1/analysis , Annexin A1/biosynthesis , Annexin A2/analysis , Annexin A2/biosynthesis , Annexin A3/analysis , Annexin A3/biosynthesis , Annexin A4/analysis , Annexin A4/biosynthesis , Annexin A5/analysis , Annexin A5/biosynthesis , Annexin A6/analysis , Annexin A6/biosynthesis , Annexins/analysis , Annexins/immunology , Antibody Specificity , Electrophoresis, Polyacrylamide Gel , Fluorescent Antibody Technique, Indirect , Ganglia, Spinal/cytology , Ganglia, Spinal/metabolism , Motor Neurons/chemistry , Neuroglia/chemistry , Neurons, Afferent/chemistry , Rabbits , Rats , Sheep , Species Specificity , Spinal Cord/cytology , Spinal Cord/metabolism , Swine
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