Decreased numbers of dendritic spines on cortical pyramidal neurons in human chronic alcoholism

Ferrer, Isidró; Fabregues, I.; Rairiz, Julia; Galofré, E

doi:10.1016/0304-3940(86)90425-8

Cited by 65 publications

(18 citation statements)

References 19 publications

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“…The effects of social deprivation in humans are unknown, although rats housed in isolation showed no difference in cortical spine densities compared to rats kept in a social environment (Connor & Diamond, 1982). Other factors which could affect spine density in schizophrenics include the effects of alcohol (Ferrer et al 1986), but this can be documented and does not concern the in-patient population described here.…”

Section: Discussionmentioning

confidence: 73%

When cortical development goes wrong: schizophrenia as a neurodevelopmental disease of microcircuits

Garey¹

2010

Journal of Anatomy

144

101

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Schizophrenia probably has a developmental origin. This review refers to three of our published series of studies related to this hypothesis: loss of dendritic spines on cerebral neocortical pyramidal neurons, decreased numerical density of glutamatergic neurons, and microgliosis. First, brains of schizophrenic patients and nonschizophrenic controls were obtained post mortem and blocks of multiple cortical areas impregnated with a Rapid Golgi method. Spines were counted on the dendrites of pyramidal neurons of which the soma was in layer III (which takes part in corticocortical connectivity) and which met strict criteria for impregnation quality. Data were obtained blind: diagnoses were only revealed by a third party after measurements were completed. The mean spine count in all cortical areas studied in the control series was 243 mm )1 of dendrite and in the schizophrenics 108. Measurements in frontal and temporal association cortex showed the greatest reduction in spine number in schizophrenia (299 in control frontal cortex and 101 in schizophrenics, and 276 mm )1 in control temporal cortex and 125 in schizophrenics). There was no correlation of spine loss with age at death. Our results support the concept of a neurodevelopmental defect in the neuropil affecting glutamatergic neurons in schizophrenia and may help to explain loss of cortical volume without loss of neurons. In a second part of our study we used an antibody to the kainate receptor subunit GluR 5 ⁄ 6 ⁄ 7 and showed a decrease in numerical density of presumed glutamatergic neurons in schizophrenic orbitofrontal cortex. Finally, as glia play a major role in the developing nervous system, we investigated whether schizophrenia was associated with glial changes in frontal and temporal cortex. Astroglia and microglia were identified in schizophrenic and control brains, using antibodies to glial fibrillary acidic protein (GFAP) and class II human leucocyte antigen (HLA-DR), respectively. Significant increases were found in microglial numerical density in schizophrenics compared with controls: 28% in frontal area 9 (115 cells mm )2 compared with 89), and a 57% increase in temporal area 22(139 cells mm )2 compared with 88). For both areas, astroglia showed no significant differences between schizophrenics and controls. No significant differences were found in cortical thickness or total neuronal numerical density between the two groups. This specific increase in numerical density of microglia in temporal and frontal cortex of chronic schizophrenics, not related to aging, could be related to possible changes in cortical neuropil architecture as revealed by loss of dendritic spines.

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Section: Discussionmentioning

confidence: 73%

When cortical development goes wrong: schizophrenia as a neurodevelopmental disease of microcircuits

Garey¹

2010

Journal of Anatomy

144

101

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“…It is possible that other homeostatic mechanisms may be compensating for the global deletion of Arc from birth, thereby maintaining both normal anxiety and DSD in Arc mutant mice. Previous studies have also shown that ethanol and exposure to other drugs of abuse, such as morphine and cocaine, caused alterations in DSD in the cortex, hippocampus, cerebellum, and nucleus accumbens of rats (Ferrer et al, 1986;Tarelo-Acuna et al, 2000;Robinson et al, 2001Robinson et al, , 2002Zhou et al, 2007).…”

Section: Discussionmentioning

confidence: 91%

Effector Immediate-Early Gene Arc in the Amygdala Plays a Critical Role in Alcoholism

Pandey

Zhang²,

Ugale³

et al. 2008

J. Neurosci.

143

186

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The immediate early gene, activity-regulated cytoskeleton-associated protein (Arc), has been implicated in synaptic plasticity. However, the role of Arc in alcoholism is unknown. Here, we report that the anxiolytic effects of acute ethanol were associated with increased brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (trkB) expression, increased phosphorylation of extracellular signalregulated kinases 1/2 (Erk1/2), Elk-1, and cAMP responsive element-binding protein (CREB), increased Arc expression, and increased dendritic spine density (DSD) in both the central amygdala (CeA) and medial amygdala (MeA) but not in the basolateral amygdala (BLA) of rats. Conversely, the anxiogenic effects of withdrawal after long-term ethanol exposure were associated with decreased BDNF and trkB expression, decreased phosphorylation of Erk1/2, Elk-1, and CREB, decreased Arc expression, and decreased DSD in both the CeA and MeA but not in the BLA of rats. We also showed that BDNF infusion into the CeA normalized phosphorylation of Erk1/2, Elk-1, and CREB, and normalized Arc expression, thereby protecting against the onset of ethanol withdrawal-related anxiety. We further demonstrated that arresting Arc expression in the CeA decreased DSD, thereby increasing anxiety-like and alcohol-drinking behaviors in control rats. These results revealed that BDNF-Arc signaling and the associated DSD in the CeA, and possibly in the MeA, may be involved in the molecular processes of alcohol dependence and comorbidity of anxiety and alcohol-drinking behaviors.

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“…Spine density is higher in the hyperstriatum of chickens which have learned a specific task than in control animals (Patel & Stewart, 1988). Spine loss has been reported as a result of various environmental factors such as exposure to alcohol (Riley & Walker, 1978;Ferrer et al, 1986), or exposure to carbon monoxide (Norton & Culver, 1977). Reduction of spine density has also been observed in diseases such as Scrapie (Hogan et al, 1987) and dementia (De Ruiter & Uylings, 1987), as well as after removal of afferent inputs (Kemp & Powell, 1971d;Ingham et al, 1989;Nitsch & Riesenberg, 1995).…”

Section: Discussionmentioning

confidence: 93%

Age-Related Changes in the Synapses of the Rat' Neostriatum

Itzev

Lolova

Lolov

et al. 2001

Archives of Physiology and Biochemistry

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By means of transmission electron microscopy, the age-related changes in axospinous (ASS) and axodendritic (ADS) synapses in the dorsal part of the rostral neostriatum in two groups of Wistar rats: young (3-month-old), and senescent (25-month-old) were examined. The changes in different parameters, characterizing the ASS and ADS: synaptic density (SD), number of synaptic vesicles (SV), number of synaptic contact zone (SCZ), and number of dendritic spines, bearing synapses (DS) were investigated morphometrically. The SD of the ASS decreased significantly during aging, but the SD of the ADS did not changed significantly. The mean area of the synaptic boutons increased significantly during aging in two types of synapses. The mean number of vesicles per synaptic bouton increased, but the number of vesicles per microm2 of synaptic bouton, and per microm3 of the neuropil decreased. The mean SCZ length increased in both types of synapses. The total SCZ length per 1000 microm2 of the neuropil, and the total area of the SCZ per 1000 microm3 of the neuropil decreased in ASS, but the same parameters of the ADS did not changed significantly. The mean number of synaptic DS per 1000 microm2 of the neropil decreased during aging, but the mean area of the synaptic DS increased. The present results support the hypothesis that the synaptic contacts change significantly during aging, and the ASS are more vulnerable during aging than the ADS.

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Decreased numbers of dendritic spines on cortical pyramidal neurons in human chronic alcoholism

Cited by 65 publications

References 19 publications

When cortical development goes wrong: schizophrenia as a neurodevelopmental disease of microcircuits

When cortical development goes wrong: schizophrenia as a neurodevelopmental disease of microcircuits

Effector Immediate-Early Gene Arc in the Amygdala Plays a Critical Role in Alcoholism

Age-Related Changes in the Synapses of the Rat' Neostriatum

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