Negative Association Between MR-Spectroscopic Glutamate Markers and Gray Matter Volume After Alcohol Withdrawal in the Hippocampus: A Translational Study in Humans and Rats.

BACKGROUND: Both chronic alcohol consumption and alcohol withdrawal lead to neural tissue damage which partly recovers during abstinence. This study investigated withdrawal-associated changes in glutamatergic compounds, markers of neuronal integrity, and gray matter volumes during acute alcohol withdrawal in the hippocampus, a key region in development and maintenance of alcohol dependence in humans and rats. METHODS: Alcohol-dependent patients (N = 39) underwent magnetic resonance imaging (MRI) and MR spectroscopy (MRS) measurements within 24 hours after the last drink and after 2 weeks of abstinence. MRI and MRS data of healthy controls (N = 34) were acquired once. Our thorough quality criteria resulted in N = 15 available spectra from the first and of N = 21 from the second measurement in patients, and of N = 19 from healthy controls. In a translational approach, chronic intermittent ethanol-exposed rats and respective controls (8/group) underwent 5 MRS measurements covering baseline, intoxication, 12 and 60 hours of withdrawal, and 3 weeks of abstinence. RESULTS: In both species, higher levels of markers of glutamatergic metabolism were associated with lower gray matter volumes in the hippocampus in early abstinence. Trends of reduced N-acetylaspartate levels during intoxication persisted in patients with severe alcohol withdrawal symptoms over 2 weeks of abstinence. We observed a higher ratio of glutamate to glutamine during alcohol withdrawal in our animal model. CONCLUSIONS: Due to limited statistical power, we regard the results as preliminary and discuss them in the framework of the hypothesis of withdrawal-induced hyperglutamatergic neurotoxicity, alcohol-induced neural changes, and training-associated effects of abstinence on hippocampal tissue integrity.

The neurometabolic fingerprint of excessive alcohol drinking.

'Omics' techniques are widely used to identify novel mechanisms underlying brain function and pathology. Here we applied a novel metabolomics approach to further ascertain the role of frontostriatal brain regions for the expression of addiction-like behaviors in rat models of alcoholism. Rats were made alcohol dependent via chronic intermittent alcohol vapor exposure. Following a 3-week abstinence period, rats had continuous access to alcohol in a two-bottle, free-choice paradigm for 7 weeks. Nontargeted flow injection time-of-flight mass spectrometry was used to assess global metabolic profiles of two cortical (prelimbic and infralimbic) and two striatal (accumbens core and shell) brain regions. Alcohol consumption produces pronounced global effects on neurometabolomic profiles leading to a clear separation of metabolic phenotypes between treatment groups, particularly. Further comparisons of regional tissue levels of various metabolites, most notably dopamine and Met-enkephalin, allow the extrapolation of alcohol consumption history. Finally, a high-drinking metabolic fingerprint was identified indicating a distinct alteration of central energy metabolism in the accumbens shell of excessively drinking rats that could indicate a so far unrecognized pathophysiological mechanism in alcohol addiction. In conclusion, global metabolic profiling from distinct brain regions by mass spectrometry identifies profiles reflective of an animal's drinking history and provides a versatile tool to further investigate pathophysiological mechanisms in alcohol dependence.

Maturation of postnatally generated olfactory bulb granule cells depends on functional γ-protocadherin expression.

γ-protocadherins (γ-pcdhs) are transmembrane receptor proteins ubiquitously expressed in the postnatal and adult mouse brain. γ-pcdhs are required for normal neuronal development as shown for spinal cord interneurons, retinal ganglion cells and cortical neurons. To test the role of γ-pcdhs during development of subventricular zone progenitor cells and their subsequent differentiation into olfactory granule cells we generated a conditional γ-pcdh(lox/lox) allele (γ-pcdh(lox/lox)) allowing for functional γ-pcdh inactivation upon lentivirus-mediated Cre-recombinase expression selectively in subventricular zone progenitor cells. While γ-pcdh loss did not alter the proliferation of subventricular zone progenitors, γ-pcdh ko progenitors that reached the main olfactory bulb showed a significant reduction in dendritic arborization and failed to develop dendritic spines. Our results suggest that olfactory bulb granule cell maturation necessitates functional γ-pcdh expression.

Laser wavelengths and oral implantology.

In modern implant dentistry there are several clinical indications for laser surgery. Different laser systems have a considerable spectrum of application in soft and hard peri-implant tissues. The literature was searched for clinical application of different laser wavelengths in peri-implant tissues: second-stage surgery of submerged implants, treatment of infrabony defects, removal of peri-implant hyperplastic overgrowths, and, possibly, the preparation of bone cavities for implant placement. This report describes the state-of-the-art application of different laser systems in modern implant dentistry for the treatment of peri-implant lesions and decontamination of implant surfaces. Our study evaluated in vitro examinations, clinical experience and long-term clinical studies. The exact selection of the appropriate laser system and wavelength was dependent on the scientific evaluation of recent literature and the level of changes in implant and tissue temperatures during laser application. The significant reduction in bacteria on the implant surface and the peri-implant tissues during irradiation and the cutting effects associated with the coagulation properties of the lasers are the main reasons for laser application in the treatment of peri-implant lesions and the successful long-term prognosis of failing oral implants. The various applications of lasers in implant dentistry are dependent on the wavelength and laser-tissue interactions.