Changes in the basal dendrites of cortical pyramidal cells from alcoholic patients--a quantitative Golgi study.

Abstract

Although a variety of pathological changes have been described in the brains of chronic alcoholic patients, there have been no studies which have addressed the question of alterations in cortical neuronal dendritic arborisation. Loss of neurons from the superior frontal gyrui and shrinkage of neurons from both the superior frontal gyrus and motor cortex has been documented in chronic alcoholic patients; these areas were chosen for this study. Using a modified rapid Golgi technique the basal dendritic arborisation of layer III pyramidal neurons was compared in 15 male alcoholic patients and 15 age-matched male controls. All parameters measuring basal dendritic arborisation were significantly less in the alcoholic cases for both the superior frontal and motor cortices. Changes in the arbor are in the terminal branches, which is consistent with other models of dendritic plasticity. Such changes may explain both permanent and reversible functional deficits in chronic alcoholic patients. Materials and methodsThe brains of 15 alcoholics and 15 controls were used in this study. These were obtained from necropsies performed in collaboration with the forensic pathologists of the Perth City Coroner's Department. The cases were all males and the controls were matched for age and postmortem delay to the alcoholics. Five of the controls had been teetotal and the remainder drank less than 20 g of alcohol per day. The alcoholic patients drank more than 120 g of alcohol per day. The information to allow categorisation of cases into "control" and "alcoholic" had been obtained from clinical notes available from previous admissions to the teaching hospitals of Perth, the results of detailed questionnaires on alcohol intake and the nutritional state provided by relatives of the deceased, and reports concerning the circumstances of death.Each case had a complete necropsy and microscopic examination of the tissues including the liver and brain. Patients who had a history of, or showed pathological evidence of neurological diseases other than those associated with alcoholism, were excluded. No cases with evidence of brain pathology (for example, infarcts, contusions) were included.

Comparison of prefrontal cell pathology between depression and alcohol dependence

“…In MDD the reduction in size is prominent in layers II and III in dlPFC and orbitofrontal cortex and appears to affect mainly the larger pyramidal cells. Interestingly, in alcoholism a reduction in the dendritic arbor of layer III pyramidal neurons has been described (Harper & Corbett, 1990a). In our studies on alcoholism in the dlPFC this cortical layer presents also the largest reduction in neuronal density.…”

“…1) and other regions in postmortem brain tissue from alcoholics (Harper & Corbett, 1990a;Harper & Kril, 1990b;Jensen & Pakkenberg, 1993;Korbo, 1999;Kril et al, 1997;Kril & Harper, 1989). More recently similar studies have also been undertaken in mood disorders (Cotter et al, 2002a;Miguel-Hidalgo et al, 2000;Öngür et al, 1998;Rajkowska et al, 1999Rajkowska et al, , 2001.…”

“…It seems, however that in the brain of alcoholics without Wernicke's encephalopathy or Korsakoff psychosis, so-called uncomplicated alcoholics, neuronal loss does not extend to other cortical areas and is rather specific to the prefrontal cortex (Harper, 1998;Jensen & Pakkenberg, 1993;Kril & Halliday, 1999). In the superior frontal gyrus the reductions in neuronal number appear to be accompanied by a loss of basal dendrites in pyramidal neurons of cortical layer III (Harper & Corbett, 1990a) suggesting that a reduction of in neuronal number might be preceded by elimination of synaptic inputs to layer III neurons. Recently, we have found in a preliminary study that the packing density of neurons in all cortical layers combined was reduced in the dlPFC in alcoholics as compared to non-psychiatric controls (unpublished results).…”

Alcohol related dementia: proposed clinical criteria

“…Moreover, many authors have described neuropathologic changes in alcoholics such as neuronal loss and neuroglial proliferation in the cerebral cortex, cerebellar degeneration, arteriosclerotic changes, and evidence of lipid emboli (Arango, 1994;Courville, 1966;Courville, 1954;Harper, 1990;Harper, 1985;Ibanez, 1995;Lynch, 1960;Mott, 1910;Ron, 1977). Unfortunately, many of these studies did not correlate neuropathologic changes with cognitive changes or alcohol consumption, thus limiting any interpretation regarding ARD.…”

Neuroimaging in alcoholism: CT and MRI results and clinical correlates

“…Ultrastructural studies have not been possible using human material. However, Spanish researchers (Ferrer etal., 1986) and Harper and Corbett (1990) have examined and measured the dendritic arbor of cortical neurons in alcoholic subjects using Golgi impregnation techniques. There was a significant reduction in the basal dendritic arbor of layer III pyramidal neurons in both the superior frontal and motor cortices.…”