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Biomedical subjects

Grazyna Rajkowska

Publications and source records attributed to Grazyna Rajkowska.

9 recordsLinked to original sources
PubMed2002

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

BACKGROUND: Reductions in glial density and enlargement of glial nuclei have been reported in the dorsolateral prefrontal cortex (dlPFC) in mood disorders. In alcohol dependence, often comorbid with depression, it is unclear whether there are changes in the density and size of glial cells in the dlPFC. METHODS: The packing density and size of Nissl-stained glial cell nuclei were analyzed postmortem in the cortical layers of the dlPFC from 21 control and 17 alcohol-dependent (Alc) subjects without Wernicke or Korsakoff syndromes. Eight Alc subjects had depressive symptoms. The density of glial cells was measured with a three-dimensional cell counting method, and the areal fraction of glial fibrillary acidic protein immunoreactivity (GFAP) was also determined. RESULTS: Glial density was reduced by 11-14% in layers V and VI and in all layers combined in the Alc group. The size of glial nuclei was decreased by 3.2% in Alc subjects. The Alc subjects with depressive symptoms showed the lowest values of density and size. There was no difference in GFAP immunoreactivity, although the lowest values were in the Alc group. CONCLUSIONS: 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.

Adolescent↗
PubMed2002

Layer-specific reductions in GFAP-reactive astroglia in the dorsolateral prefrontal cortex in schizophrenia.

Neuroimaging studies have implicated the prefronto-striatal loop as a substrate for the cognitive deficits in schizophrenia (SCHZ). Postmortem morphometric studies reveal that layers III and V of the dorsolateral prefrontal cortex (dlPFC), which gave rise to glutamatergic projections to neostriatum, demonstrate the most structural pathology in this region of the SCHZ. These neuronal alterations in SCHZ are not accompanied by marked glial changes as revealed by Nissl staining. We examined the glial-type specific pathology in SCHZ by analyzing the glial fibrillary acidic protein- (GFAP) immunoreactive astroglia in contrast to the Nissl-stained general pool of glial cells in dlPFC (area 9) from 9 subjects with SCHZ and 15 psychiatrically normal control subjects. In layer V of the dlPFC in SCHZ, there was a significant 32% reduction in the GFAP-area fraction, 81% increase in the density of the GFAP-positive cell bodies and a 14% decrease in the width of the cortical layer V, as compared to the control subjects. None of these parameters were affected in layers III and IV in the SCHZ. Therefore, only subtle, type- and layer-specific glial pathology is present in the dlPFC in SCHZ. Astroglial pathology in dlPFC may reflect disturbances of the neuron-glia interactions in layer V and may be related to the dysfunctional prefronto-striatal circuits, dopaminergic alterations and cognitive pathology in SCHZ.

Adult↗
PubMed2002

Neurokinin-1 receptors are decreased in major depressive disorder.

Treatment with an antagonist at the neurokinin-1 (NK-1) receptor may alleviate depression, however the brain region(s) in which the NK-1 receptor antagonist exerts its therapeutic effect is unknown. [125I]BH-Substance P was used to measure NK-1 receptors postmortem in cytoarchitectonically defined areas of rostral orbitofrontal cortex (Brodmann's area 47) of subjects with major depressive disorder (n = 12, six females) and psychiatrically normal subjects (n = 11, five females). Six subjects with depression died by suicide. Subjects with depression showed decreased binding to NK-1 receptors across all cortical layers (p = 0.024). The pathophysiology of depression, and the reported therapeutic benefit of NK-1 receptor antagonists, may thus involve NK-1 receptors in prefrontal cortex.

Adult↗
PubMed2002

Cell pathology in bipolar disorder.

OBJECTIVES: The objective of this paper is to review findings of morphometric postmortem studies conducted on tissues from subjects with bipolar disorder (BPD) to demonstrate that impairments of cell morphology and resilience may underlie the neurobiology of BPD. METHODS: Reports of alterations in number, density and size of neurons and glial cells in BPD are reviewed. Owing to the low number of postmortem studies on cellular pathology in BPD, abstracts of recent symposia are also discussed. RESULTS AND CONCLUSIONS: In BPD. significant reductions in the volume of several brain regions, as well as region- and layer-specific reductions in the number, density and/or size of neurons and glial cells have been demonstrated. Moreover, the results of recent clinical and preclinical studies investigating the molecular and cellular targets of mood stabilizing and antidepressant medications provide intriguing possibilities that impairments in neuroplasticity and cellular resilience may underlie the neurobiology of BPD. Future studies will likely examine the role of both genetic and environmental factors in the pathogenesis and cellular changes in BPD.

Bipolar Disorder↗
PubMed2002

Cell pathology in mood disorders.

In new, exciting, neuroanatomic studies on postmortem tissues from patients with mood disorders, quantitative cytomorphologic differences can be shown at the microscopic level. These investigations provide direct evidence that mood disorders are characterized by marked reductions in glial cell number and density in addition to subtle alterations in the density and size of cortical neurons in frontolimbic brain regions. Importantly, this corresponds with clinical neuroimaging studies and preclinical animal studies that suggest cell atrophy, cell loss, or impairments in neuroplasticity and cellular resilience may underlie the neurobiology of major depressive disorder and bipolar manic-depressive disorder. Because this represents a departure from modern efforts to understand mood disorders, published reports are scarce and based on rather small sample sizes. This article reviews the current findings from postmortem studies on glial and neuronal cell counts in primary mood disorders and discusses a possible link between cellular changes and the action of psychotherapeutic drugs.

Brain↗
PubMed2002

Morphological brain changes in depression: can antidepressants reverse them?

Structural neuroimaging and postmortem histopathological studies of the brain have revealed morphological changes in cortical and subcortical regions in individuals diagnosed with depression. Moreover, these regions are known to be functionally altered in mood disorders. This indicates that the morphological changes might be directly involved in the pathophysiology of depression, and implies that antidepressants may be able to regulate or reverse the detected structural abnormalities. Work with animal models has shown that antidepressants are capable of inducing structural alterations in dendrites and axons and changes in the numbers of neural cells. However, there have been no studies in the human brain that have directly addressed whether antidepressant treatment can reverse or regulate the depression-related structural changes. Nevertheless, experience with lithium in bipolar disorder and antipsychotics in schizophrenia suggests that treatment with psychotropic drugs can result in structural changes that are consistent with reversion towards normal values. Clearly, ascertaining the role of the reversal of structural changes in the therapeutic actions of antidepressants will require further longitudinal studies and careful comparisons between those patients with mood disorder who are treated with antidepressants and those who are not.

Animals↗
PubMedDate not supplied

Differential expression of alpha2-adrenoceptor vs. imidazoline binding sites in postmortem orbitofrontal cortex and amygdala of depressed subjects.

Clonidine is a well established antihypertensive agent that is also used effectively to treat a variety of psychiatric disorders. Clonidine is a prototypic imidazoline compound that acts as an alpha(2)-adrenergic agonist but possesses nearly equivalent affinity for non-adrenergic imidazoline binding sites (I-sites). Receptor autoradiography of [(3)H]-clonidine binding presented herein compares densities of alpha(2)-adrenoceptors and I-sites (under a noradrenergic-mask) in Brodmann's area 47 of the left orbitofrontal cortex (OFC) and in six amygdaloid nuclei of subjects with major depression (n=12) vs. controls with no psychiatric history (n=11). Postmortem diagnoses were made from psychiatric interviews with next-of-kin. [(3)H]-Clonidine binding to alpha(2)-adrenoceptors in each of six OFC layers was lower, although not reaching statistical significance in any one layer by multivariate analysis, in depressives vs. control subjects. Binding to I-sites was conversely higher in depressives compared to control OFC layers, but did not reach statistical significance alone. However, the ratios of alpha(2)-adrenoceptor : I-sites in all six layers of OFC of depressed subjects were nearly half that of control subjects (P<0.008). In amygdalas from a different group of depressed patients there were no changes in alpha(2)-adrenoceptors or I-sites, or their ratios, compared with controls. The results support previous western blot data indicating a cortex-selective shift away from alpha(2)AR towards I-site preponderance in depressed patients.

Adrenergic alpha-Agonists↗
PubMedDate not supplied

Comparison of prefrontal cell pathology between depression and alcohol dependence.

Chronic alcohol abuse is often co-morbid with depression symptoms and in many cases it appears to induce major depressive disorder. Structural and functional neuroimaging has provided evidence supporting some degree of neuropathological convergence of alcoholism and mood disorders. In order to understand the cellular neuropathology of alcohol dependence and mood disorders, postmortem morphometric studies have tested the possibility of alterations in the number and size of cells in the prefrontal cortex and other brain regions. The present review compares the cell pathology in the prefrontal cortex between alcohol dependence and depression, and reveals both similarities and differences. One of the most striking similarities is that, although pathology affects both neuronal and glial cells, effects on glia are more dramatic than on neurons in both alcohol dependence comorbid with depression and idiopathic depression. Moreover, prefrontal cortical regions are commonly affected in both depression and alcoholism. However, the cellular changes are more prominent and spread across cortical layers in alcohol dependent subjects than in subjects with mood disorders, and changes in glial nucleus size are opposite in alcoholism and depression. It could be argued that one defining factor in the manifestation of the depressive pathology is a reduction in the glial distribution in the dlPFC that is reflected in a reduced glial density. In alcoholism reduced glial nuclear size might be related to the cytotoxic effects of prolonged alcohol exposure, while in MDD, in the absence of alcohol abuse, other processes might be responsible for the increase in average size of glial nuclei. In either case abnormal function related to glial reduction would be associated with depression due to insufficient glial support to the surrounding neurons.

Alcoholism↗