Re-investigating the effects of chronic smoking on the pathology of alcohol-related human brain damage.

Both pathological and neuroimaging studies have shown that chronic alcohol abuse causes generalized white matter, but limited gray matter, volume loss. Recent neuroimaging studies suggest that tobacco smoking also causes brain atrophy in both alcoholics and neurologically normal individuals. However, a recent pathological study, employing a manual technique to determine regional volumes, found no significant effects of smoking on either global or selected regional gray matter volumes in smokers or smoking alcoholics. Here a high-resolution computerized method was employed in the same cohort to evaluate four regions where neuroimaging studies have found atrophy in smokers and alcoholics: insula, thalamus, prefrontal cortex, and anterior cingulate cortex. Brain images from 44 cases comprising 16 non-smoking controls, nine smoking controls, eight non-smoking alcoholics, and 11 smoking alcoholics were quantified. No significant differences between the groups were found, although the alcoholic groups tended to have smaller volumes in most regions. Furthermore, there were no smoking or interactive effects, and no correlation between gray matter volumes and either tobacco pack-years or lifetime alcohol consumption. These results do not support the hypotheses that tobacco smoking causes gray matter loss or that smoking potentiates gray matter atrophy in chronic alcoholics.

Human adult neurogenesis across the ages: An immunohistochemical study.

AIMS: Neurogenesis in the postnatal human brain occurs in two neurogenic niches; the subventricular zone (SVZ) in the wall of the lateral ventricles and the subgranular zone (SGZ) of the hippocampus. The extent to which this physiological process continues into adulthood is an area of ongoing research. This study aimed to characterize markers of cell proliferation and assess the efficacy of antibodies used to identify neurogenesis in both neurogenic niches of the human brain. METHODS: Cell proliferation and neurogenesis were simultaneously examined in the SVZ and SGZ of 23 individuals aged 0.2-59 years, using immunohistochemistry and immunofluorescence in combination with unbiased stereology. RESULTS: There was a marked decline in proliferating cells in both neurogenic niches in early infancy with levels reaching those seen in the adjacent parenchyma by 4 and 1 year of age, in the SVZ and SGZ, respectively. Furthermore, the phenotype of these proliferating cells in both niches changed with age. In infants, proliferating cells co-expressed neural progenitor (epidermal growth factor receptor), immature neuronal (doublecortin and beta III tubulin) and oligodendrocytic (Olig2) markers. However, after 3 years of age, microglia were the only proliferating cells found in either niche or in the adjacent parenchyma. CONCLUSIONS: This study demonstrates a marked decline in neurogenesis in both neurogenic niches in early childhood, and that the sparse proliferating cells in the adult brain are largely microglia.

The effects of chronic smoking on the pathology of alcohol-related brain damage.

Both pathological and neuroimaging studies demonstrate that chronic alcohol abuse causes brain atrophy with widespread white matter loss limited gray matter loss. Recent neuroimaging studies suggest that tobacco smoking also causes brain atrophy in both alcoholics and neurologically normal individuals; however, this has not been confirmed pathologically. In this study, the effects of smoking and the potential additive effects of concomitant alcohol and tobacco consumption were investigated in autopsied human brains. A total of 44 cases and controls were divided into four groups: 16 non-smoking controls, nine smoking controls, eight non-smoking alcoholics, and 11 smoking alcoholics. The volumes of 26 gray and white matter regions were measured using an established point-counting technique. The results showed trends for widespread white matter loss in alcoholics (p < 0.007) but no effect on gray matter regions. In contrast, smoking alone had no effect on brain atrophy and the combination of smoking and alcohol showed no additional effect. Neuronal density was analyzed as a more sensitive assay of gray matter integrity. Similar to the volumetric analysis, there was a reduction in neurons (29%) in the prefrontal cortex of alcoholics, albeit this was only a trend when adjusted for potential confounders (p < 0.06). There were no smoking or combinatorial effects on neuronal density in any of the three regions examined. These results do not support the hypothesis that smoking exacerbates alcohol-related brain damage. The trends here support previous studies that alcohol-related brain damage is characterized by focal neuronal loss and generalized white matter atrophy. These disparate effects suggest that two different pathogenic mechanisms may be operating in the alcoholic brain. Future studies using ultrastructural or molecular techniques will be required to determine if smoking has more subtle effects on the brain and how chronic alcohol consumption leads to widespread white matter loss.

The NSW brain tissue resource centre: Banking for alcohol and major neuropsychiatric disorders research.

The New South Wales Brain Tissue Resource Centre (NSWBTRC) at the University of Sydney (Australia) is an established human brain bank providing tissue to the neuroscience research community for investigations on alcohol-related brain damage and major psychiatric illnesses such as schizophrenia. The NSWBTRC relies on wide community engagement to encourage those with and without neuropsychiatric illness to consent to donation through its allied research programs. The subsequent provision of high-quality samples relies on standardized operational protocols, associated clinical data, quality control measures, integrated information systems, robust infrastructure, and governance. These processes are continually augmented to complement the changes in internal and external governance as well as the complexity and diversity of advanced investigation techniques. This report provides an overview of the dynamic process of brain banking and discusses the challenges of meeting the future needs of researchers, including synchronicity with other disease-focus collections.

The effects of chronic alcoholism on cell proliferation in the human brain.

Neurogenesis continues in the human subventricular zone and to a lesser extent in the hippocampal subgranular zone throughout life. Subventricular zone-derived neuroblasts migrate to the olfactory bulb where survivors become integrated as interneurons and are postulated to contribute to odor discrimination. Adult neurogenesis is dysregulated in many neurological, neurovascular and neurodegenerative diseases. Alcohol abuse can result in a neurodegenerative condition called alcohol-related brain damage. Alcohol-related brain damage manifests clinically as cognitive dysfunction and the loss of smell sensation (hyposmia) and pathologically as generalized white matter atrophy and focal neuronal loss. The exact mechanism linking chronic alcohol intoxication with alcohol-related brain damage remains largely unknown but rodent models suggest that decreased neurogenesis is an important component. We investigated this idea by comparing proliferative events in the subventricular zone and olfactory bulb of a well-characterized cohort of 15 chronic alcoholics and 16 age-matched controls. In contrast to the findings in animal models there was no difference in the number of proliferative cell nuclear antigen-positive cells in the subventricular zone of alcoholics (mean±SD=28.7±20.0) and controls (27.6±18.9, p=1.0). There were also no differences in either the total (p=0.89) or proliferative cells (p=0.98) in the granular cell layer of the olfactory bulb. Our findings show that chronic alcohol consumption does not affect cell proliferation in the human SVZ or olfactory bulb. In fact only microglial proliferation could be demonstrated in the latter. Therefore neurogenic deficits are unlikely to contribute to hyposmia in chronic alcoholics.