Glia pathology in the prefrontal cortex in alcohol dependence with and without depressive symptoms

Miguel-Hidalgo, José Javier; Wei, Jinrong; Andrew, Michael E.; Overholser, James C.; Jurjus, George J.; Stockmeier, Craig A.; Rajkowska, Grażyna

doi:10.1016/s0006-3223(02)01439-7

Cited by 134 publications

(106 citation statements)

References 63 publications

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“…These data suggest that increased density only occurred in a subset of the NAcore astrocyte population, which is consistent with earlier reports showing that only a subset of ALDH1L1 þ cells co-express GFAP (Cahoy et al, 2008). Additionally, a similar finding of altered GFAP þ astrocyte density, yet unchanged GFAP expression, was previously observed in EtOH-dependent human brain (Miguel-Hidalgo et al, 2002). While the specific ramifications of increased GFAP þ astrocyte density concerning motivated behavior remain unknown, it has been shown that increased astrocyte density can mitigate the impact of neurotoxic peroxide production that occurs during cytochrome P450-mediated metabolism of EtOH (Desagher et al, 1996).…”

Section: Behavioral Relevance Of Astrocyte Densitysupporting

confidence: 92%

“…Additionally, rat strains that had selfadministered more morphine expressed more GFAP in the ventral tegmental area (Beitner-Johnson et al, 1993). In the prefrontal cortex, prelimbic GFAP þ astrocyte density was lower in rats that exhibited higher ethanol (EtOH) preference (Miguel-Hidalgo, 2005) while dorsolateral astrocyte density was lower in EtOH-dependent humans (Miguel-Hidalgo et al, 2002). These studies illustrate that astrocytes respond to commonly abused substances in a region-specific manner.…”

Section: Introductionmentioning

confidence: 81%

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Rat Nucleus Accumbens Core Astrocytes Modulate Reward and the Motivation to Self-Administer Ethanol after Abstinence

Bull

Freitas

Zou

et al. 2014

Neuropsychopharmacol

120

106

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Our understanding of the active role that astrocytes play in modulating neuronal function and behavior is rapidly expanding, but little is known about the role that astrocytes may play in drug-seeking behavior for commonly abused substances. Given that the nucleus accumbens is critically involved in substance abuse and motivation, we sought to determine whether nucleus accumbens astrocytes influence the motivation to self-administer ethanol following abstinence. We found that the packing density of astrocytes that were expressing glial fibrillary acidic protein increased in the nucleus accumbens core (NAcore) during abstinence from EtOH selfadministration. No change was observed in the nucleus accumbens shell. This increased NAcore astrocyte density positively correlated with the motivation for ethanol. Astrocytes can communicate with one another and influence neuronal activity through gap-junction hemichannels. Because of this, the effect of blocking gap-junction hemichannels on the motivation for ethanol was examined. The motivation to self-administer ethanol after 3 weeks abstinence was increased following microinjection of gap-junction hemichannel blockers into the NAcore at doses that block both neuronal and astrocytic channels. In contrast, no effect was observed following microinjection of doses that are not thought to block astrocytic channels or following microinjection of either dose into the nucleus accumbens shell. Additionally, the motivation for sucrose after 3 weeks abstinence was unaffected by NAcore gap-junction hemichannel blockers. Next, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) were selectively expressed in NAcore astrocytes to test the effect of astrocyte stimulation. DREADD activation increased cytosolic calcium in primary astrocytes, facilitated responding for rewarding brain stimulation, and reduced the motivation for ethanol after 3 weeks abstinence. This is the first work to modulate drug-seeking behavior with astrocyte-specific DREADDs. Taken together, our findings demonstrate that NAcore astrocytes can shape the motivation to self-administer ethanol; suggesting that the development of ligands which selectively stimulate astrocytes may be a successful strategy to abate ethanol-seeking behavior.

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Section: Behavioral Relevance Of Astrocyte Densitysupporting

confidence: 92%

Section: Introductionmentioning

confidence: 81%

Rat Nucleus Accumbens Core Astrocytes Modulate Reward and the Motivation to Self-Administer Ethanol after Abstinence

Bull

Freitas

Zou

et al. 2014

Neuropsychopharmacol

120

106

View full text Add to dashboard Cite

show abstract

“…Excess extracellular fluid is presumed to be quickly drained into the ventricular system to be absorbed by venous sinuses, but excretion of fluid into vasculature of the brain parenchyma has also been proposed (Bloch et al, 2006). Shrinkage of brain cells and their processes (Obernier et al, 2002) might occur in the absence of gross tissue volume loss (Miguel-Hidalgo et al, 2002). Alternatively, tissue volume loss in this study sample may have been too small or too widely distributed to detect in any single region.…”

Section: Discussionmentioning

confidence: 92%

A Mechanism of Rapidly Reversible Cerebral Ventricular Enlargement Independent of Tissue Atrophy

Zahr

Mayer

Rohlfing

et al. 2013

Neuropsychopharmacol

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Ventricular enlargement, a common in vivo marker of aging, disease, and insult, is presumed to reflect atrophy of surrounding brain regions. Pathological mechanisms underlying ventricular enlargement, however, are likely specific to the condition under investigation. Here, multimodal imaging, incorporating structural magnetic resonance imaging (MRI), MR spectroscopy (MRS), and diffusion weighted imaging (DWI), was used in rats exposed to binge ethanol (EtOH) to provide insight into a mechanism of reversible ventricular enlargement. During intoxication, MRI revealed expansion of ventricles, but volume changes in dorsal or ventral hippocampi, caudateputamen, or thalamus were not detectible. MRS of whole-brain parenchyma showed decreases in N-acetylasparate (NAA) and tissue water T2, and increases in choline-containing compounds (Cho). DWI showed decreased diffusivity selective to the thalamus. All MR parameters returned to baseline with 7 days of recovery. Rapid recovery of ventricular volume and the absence of detectable tissue volume reductions in brain regions adjacent to ventricles argue against atrophy as a mechanism of ventricular expansion. Decreased tissue water T2 and decreased thalamic diffusivity suggest lower tissue water content and a role for both NAA and Cho, as osmolytes is proposed. Together, these data support a model of fluid redistribution during acute EtOH intoxication and recovery to account for rapid ventricular volume changes.

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“…This gene is abundantly expressed in glial cells of the central nervous system and can be used as a marker for glial cell density and health. It is decreased in the FC of human adult alcoholics and more so in alcoholics with depressive symptoms (Miguel-Hidalgo et al, 2002). Humans with a history of chronic alcoholism have been found to have substantial glial pathology in the FC irrespective of current alcohol use or liver pathology (Cullen & Halliday, 1994).…”

Section: Within-region Analysismentioning

confidence: 99%

Functional gene expression differences between inbred alcohol-preferring and –non-preferring rats in five brain regions

Kimpel

Strother

McClintick

et al. 2007

Alcohol

107

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The objective of this study was to determine if there are innate differences in gene expression in selected CNS regions between inbred alcohol-preferring (iP) and -non-preferring (iNP) rats. Gene expression was determined in the nucleus accumbens (ACB), amygdala (AMYG), frontal cortex (FC), caudate-putamen (CPU), and hippocampus (HIPP) of alcohol-naïve adult male iP and iNP rats, using Affymetrix Rat Genome U34A microarrays (n = 6/strain). Using Linear Modeling for Microarray Analysis with a false discovery rate threshold of 0.1, there were 16 genes with differential expression in the ACB, 54 in the AMYG, 8 in the FC, 24 in the CPU, and 21 in the HIPP. When examining the main effect of strain across regions, 296 genes were differentially expressed. Although the relatively small number of genes found significant within individual regions precluded a powerful analysis for over-represented Gene Ontology categories, the much larger list resulting from the main effect of strain analysis produced 17 over-represented categories (P <.05), including axon guidance, gliogenesis, negative regulation of programmed cell death, regulation of programmed cell death, regulation of synapse structure function, and transmission of nerve impulse. Co-citation analysis and graphing of significant genes revealed a network involved in the neuropeptide Y (NPY) transmitter system. Correlation of all significant genes with those located within previously established rat alcohol QTLs revealed that of the total of 313 significant genes, 71 are located within such QTLs. The many regional and overall gene expression differences between the iP and iNP rat lines may contribute to the divergent alcohol drinking phenotypes of these rats.

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Glia pathology in the prefrontal cortex in alcohol dependence with and without depressive symptoms

Abstract: Alcohol dependence is characterized by decreases in both density and size of glia in the dlPFC. Glial pathology may be more severe in Alc subjects with depressive symptoms.

Cited by 134 publications

References 63 publications

Rat Nucleus Accumbens Core Astrocytes Modulate Reward and the Motivation to Self-Administer Ethanol after Abstinence

Rat Nucleus Accumbens Core Astrocytes Modulate Reward and the Motivation to Self-Administer Ethanol after Abstinence

A Mechanism of Rapidly Reversible Cerebral Ventricular Enlargement Independent of Tissue Atrophy

Functional gene expression differences between inbred alcohol-preferring and –non-preferring rats in five brain regions

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