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1.
Mol Psychiatry ; 22(12): 1746-1758, 2017 Dec.
Article in English | MEDLINE | ID: mdl-27573876

ABSTRACT

Epigenetic processes have been implicated in the pathophysiology of alcohol dependence, but the specific molecular mechanisms mediating dependence-induced neuroadaptations remain largely unknown. Here, we found that a history of alcohol dependence persistently decreased the expression of Prdm2, a histone methyltransferase that monomethylates histone 3 at the lysine 9 residue (H3K9me1), in the rat dorsomedial prefrontal cortex (dmPFC). Downregulation of Prdm2 was associated with decreased H3K9me1, supporting that changes in Prdm2 mRNA levels affected its activity. Chromatin immunoprecipitation followed by massively parallel DNA sequencing showed that genes involved in synaptic communication are epigenetically regulated by H3K9me1 in dependent rats. In non-dependent rats, viral-vector-mediated knockdown of Prdm2 in the dmPFC resulted in expression changes similar to those observed following a history of alcohol dependence. Prdm2 knockdown resulted in increased alcohol self-administration, increased aversion-resistant alcohol intake and enhanced stress-induced relapse to alcohol seeking, a phenocopy of postdependent rats. Collectively, these results identify a novel epigenetic mechanism that contributes to the development of alcohol-seeking behavior following a history of dependence.


Subject(s)
Alcohol Drinking/metabolism , Alcoholism/metabolism , Compulsive Behavior/metabolism , DNA-Binding Proteins/metabolism , Epigenesis, Genetic , Histone-Lysine N-Methyltransferase/metabolism , Transcription Factors/metabolism , Alcohol Drinking/genetics , Alcohol Drinking/pathology , Alcoholism/genetics , Alcoholism/pathology , Animals , Central Nervous System Depressants/administration & dosage , Compulsive Behavior/genetics , Compulsive Behavior/pathology , Disease Models, Animal , Disease Susceptibility/metabolism , Drug-Seeking Behavior/physiology , Ethanol/administration & dosage , Male , Neurons/metabolism , Neurons/pathology , Prefrontal Cortex/drug effects , Prefrontal Cortex/metabolism , Prefrontal Cortex/pathology , RNA, Messenger/metabolism , Rats, Wistar , Self Administration , Stress, Psychological
2.
Environ Pollut ; 126(3): 353-61, 2003.
Article in English | MEDLINE | ID: mdl-12963296

ABSTRACT

Increased deposition of atmospheric N largely from intensive agriculture is affecting biodiversity and the composition of natural and semi-natural vegetation in Europe. The value of species based bioindicators such as the Ellenberg N index and measurements of total tissue N and free amino acids in key plant species, is described with reference to a mixed woodland downwind of a livestock farm in the Scottish Borders, operated for over 20 years with a measured spatial gradient of ammonia concentration (29-1.5 microg m(-3)). All the indicators examined showed a relationship with N deposition and provided some indication of vegetation change. Total tissue N and arginine concentrations were most closely linked with ammonia concentrations and N deposition, with r(2) values of >0.97 and >0.78 respectively.


Subject(s)
Air Pollutants/analysis , Environmental Monitoring/methods , Nitrogen/analysis , Plant Leaves/chemistry , Trees , Amino Acids/analysis , Ammonia/analysis , Animals , Animals, Domestic , Ecosystem , Poultry , Time Factors
3.
Environ Pollut ; 119(1): 9-21, 2002.
Article in English | MEDLINE | ID: mdl-12125733

ABSTRACT

The marker variables, Ellenberg Nitrogen Index, nitrous oxide and nitric oxide fluxes and foliar nitrogen, were used to define the impacts of NH3 deposition from nearby livestock buildings on species composition of woodland ground flora, using a woodland site close to a major poultry complex in the UK. The study centred on 2 units in close proximity to each other, containing 350,000 birds, and estimated to emit around 140,000 kg N year(-1) as NH3. Annual mean concentrations of NH3 close to the buildings were very large (60 microg m(-3)) and declined to 3 microg m(-3) at a distance of 650 m from the buildings. Estimated total N deposition ranged from 80 kg N ha(-1) year(-1) at a distance of 30 m to 14 kg N ha(-1) year(-1) at 650 m downwind. Emissions of N2O and NO were 56 and 131 microg N m(-2) h(-1), respectively at 30 m and 13 and 80 microg N m(-2) h(-1), respectively at 250 m downwind of the livestock buildings. Species number in woodland ground flora downwind of the buildings remained fairly constant for a distance of 200 m from the units then increased considerably, doubling at a distance of 650 m. Within the first 200 m downwind, trends in plant species composition were hard to discern because of variations in tree canopy composition and cover. The mean Ellenberg N Index ranged from 6.0 immediately downwind of the livestock buildings to 4.8 at 650 m downwind. The mean abundance weighted Ellenberg N Index also declined with distance from the buildings. Tissue N concentrations in trees, herbs and mosses were all large, reflecting the substantial ammonia emissions at this site. Tissue N content of ectohydric mosses ranged from approximately 4% at 30 m downwind to 1.6% at 650 m downwind. An assessment of the relative merits of the three marker variables concludes, that while Ellenberg Index and trace gas fluxes of N2O and NO give broad indications of impacts of ammonia emissions on woodland vegetation, the application of a critical foliar N content for ectohydric mosses is the most useful method for providing spatial information which could be of value to policy developers and planners.


Subject(s)
Agriculture , Ammonia/adverse effects , Nitric Oxide/analysis , Nitrogen/analysis , Nitrous Oxide/analysis , Trees , Ammonia/analysis , Animals , Bryopsida/chemistry , Free Radical Scavengers/analysis , Plant Leaves/chemistry , Poultry
4.
Environ Pollut ; 88(2): 193-205, 1995.
Article in English | MEDLINE | ID: mdl-15091560

ABSTRACT

Atmospheric deposition of fixed nitrogen as nitrate and ammonium in rain and by dry deposition of nitrogen dioxide, nitric acid and ammonia has increased throughout Europe during the last two decades, from 2-6 kg N ha(-1) year(-1) to 15-60 kg N ha(-1) year(-1). The nitrogen contents of bryophytes and the ericaceous shrub Calluna vulgaris have been measured at a range of sites, with the objective of showing the degree to which nitrogen deposition is reflected in foliar plant nitrogen. Tissue nitrogen concentrations of herbarium bryophyte samples and current samples of the same species collected from the same sites were compared. No significant change in tissue nitrogen was recorded at a remote site in north-west Scotland where nitrogen inputs are small (< 6 kg N ha(-1) year(-1)). Significant increases in tissue N occurred at four sites ranging from 38% in central Scotland to 63% in Cumbria where nitrogen inputs range from 15 to 30 kg N ha(-1) year(-1). The relationships found between the estimated input of atmospheric nitrogen and the tissue nitrogen content of the selected bryophytes and Calluna at the sites investigated were found to be generally linear and fitted the form N(tissue) = 0.62 + 0.022 N(dep) for bryophytes and N(tissue) = 0.83 + 0.045 N(dep) for Calluna. There was thus an increase in total tissue nitrogen of 0.02 mg g(-1) dry weight for bryophytes and 0.045 mg g(-1) dry weight for Calluna for an increase in atmospheric nitrogen deposition of 1 kg ha(-1) year(-1). The lowest concentrations were found in north-west Scotland and the highest in Cumbria and the Breckland heaths of East Anglia, both areas of high atmospheric nitrogen deposition (30-40 kg N ha(-1) year(-1)). The implications of increased tissue nitrogen content in terms of vegetation change are discussed. Changes in atmospheric nitrogen deposition with time were also examined using measured values and values inferred from tissue nitrogen content of mosses. The rate of increase in nitrogen deposition is not linear over the 90-year period, and the increases were negligible over the period 1880-1915. However, during the period 1950 to 1990 the data suggest an increase in nitrogen deposition of 2 kg N ha(-1) every 10 years.

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