Postmortem studies in mood disorders indicate altered numbers of neurons and glial cells

Rajkowska, Grażyna

doi:10.1016/s0006-3223(00)00950-1

Cited by 760 publications

(466 citation statements)

References 87 publications

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“…A number of studies suggest that subjects with affective disorders show morphological changes in the brain, including atrophy of neurons and reduction in volumes of PFC and hippocampus (Sheline et al, 1996;Drevets et al, 1997Drevets et al, , 1999Bremner et al, 2000). Several postmortem brain studies also suggest reductions in cell number and in density and size of cortical and hippocampal neurons (Rajkowska, 1997(Rajkowska, , 2000Benes et al, 1998;Rajkowska et al, 1999Rajkowska et al, , 2001. Altered brain structures have also been demonstrated in brain of suicide subjects (Altschuler et al, 1990;Rajkowska, 1997;Rajkowska et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Lower Phosphoinositide 3-Kinase (PI 3-kinase) Activity and Differential Expression Levels of Selective Catalytic and Regulatory PI 3-Kinase Subunit Isoforms in Prefrontal Cortex and Hippocampus of Suicide Subjects

Dwivedi

Rizavi

Teppen

et al. 2007

Neuropsychopharmacol

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Phosphoinositide 3 (PI 3)-kinase is one of the key signaling enzymes that participates in a myriad of physiological functions in brain and is utilized by neurotrophins to mediate neuronal plasticity, cell survival, and inhibition of apoptosis for several neuronal subtypes. Our recent demonstration that expression of neurotrophic factors and activation of the receptor tyrosine kinase B are significantly altered in postmortem brain of suicide subjects led us to examine whether suicide brain is associated with alterations in PI 3-kinase signaling. In prefrontal cortex (PFC), hippocampus, and cerebellum of suicide (n ¼ 28) and nonpsychiatric control (n ¼ 21) subjects we examined catalytic activation of PI 3-kinase, and mRNA and protein levels of regulatory (p85a, p85b) and catalytic (p110a, p110b) subunits of PI 3-kinase. It was observed that the catalytic activity of PI 3-kinase was significantly reduced in PFC and hippocampus of suicide subjects compared with nonpsychiatric control subjects. Competitive PCR analysis revealed significantly reduced mRNA expression of p85b and p110a and increased expression of p85a subunit isoforms in PFC and hippocampus of suicide subjects. Alterations in these catalytic and regulatory subunits were accompanied by changes in their respective protein levels. These changes were not present in cerebellum of suicide subjects. Also, these changes were present in all suicide subjects irrespective of psychiatric diagnosis. Our findings of reduced activation and altered expression of specific PI 3-kinase regulatory and catalytic subunit isoforms demonstrate abnormalities in this signaling pathway in postmortem brain of suicide subjects and suggest possible involvement of aberrant PI 3-kinase signaling in the pathogenic mechanisms of suicide.

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Section: Discussionmentioning

confidence: 99%

Lower Phosphoinositide 3-Kinase (PI 3-kinase) Activity and Differential Expression Levels of Selective Catalytic and Regulatory PI 3-Kinase Subunit Isoforms in Prefrontal Cortex and Hippocampus of Suicide Subjects

Dwivedi

Rizavi

Teppen

et al. 2007

Neuropsychopharmacol

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“…The reported antidepressant-induced neurogenesis in the hippocampus may be central to the antidepressive properties of antidepressant medications , and this neurogenesis is possibly at least partly due to BDNF accumulation. Accordingly, a stress-induced reduction of hippocampal volumes (Sheline, 2000) and BDNF may be central to the development of depressive mood states (Rajkowska, 2000;Altar, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…New experimental evidence suggests that mood disorders, which have traditionally been conceptualized as neurochemical disorders, are also associated with impairments of structural plasticity and cellular resilience (Manji et al, 2003). Based on clinical and animal studies, it has been suggested that mood disorders are associated with neuronal atrophy and neuronal cell loss , especially in the hippocampus (Sheline, 2000) and cerebral cortex (Rajkowska, 2000). Therefore, the issue of neuroprotection and neurotrophins is recognized as an important new lead in the quest for a deeper understanding of mood disorders and the mechanisms of action of antidepressants and mood stabilizers (Duman et al, 1997;Altar, 1999).…”

Section: Introductionmentioning

confidence: 99%

BDNF Serum Concentrations in Healthy Volunteers are Associated with Depression-Related Personality Traits

Lang

Hellweg

Gallinat

2004

Neuropsychopharmacol

199

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The issue of neurotrophins is recognized as a new lead in the quest for a deeper understanding of mood disorders. This hypothesis has emerged from experimental evidence suggesting that antidepressant drugs might work by a neuroprotective effect through the stimulation of the neurotrophin expression in distinct regions of the CNS. Endogenous levels of BDNF protein were measured in the serum samples of 118 healthy unrelated volunteers (64 male, 54 female, age: 42.1713.0 years), and the NEO-FFI has been performed in all subjects. BDNF serum values amounted to 16.377.3 ng/ml. BDNF concentration correlated significantly with age (r ¼ 0.182, p ¼ 0.048), but showed no gender differences (male 16.177.2, female 16.577.4 ng/ml). A negative correlation between the BDNF serum concentration and the depression-related factor neuroticism (r ¼ À0.212, p ¼ 0.022) has been found. Low BDNF levels in healthy humans with depressive personality traits might constitute a risk marker, reflecting a personality profilethat is linked to vulnerability to mood disorders. These results provide further support for the hypothesis that BDNF may be central to the development of depressive mood states.

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“…16 In addition, the prefrontal cortex has been postulated to have a role in the neuropathology in depression. 85 On the other hand, there is a paucity of genetic studies on depression and neurotrophins, 86,87 and they are essentially negative. Thus, involvement of BDNF in depression requires further studies.…”

Section: Bdnf and Depressionmentioning

confidence: 99%

BDNF in schizophrenia, depression and corresponding animal models

2005

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Understanding the etiology and pathogenesis schizophrenia and depression is a major challenge facing psychiatry. One hypothesis is that these disorders are secondary to a malfunction of neurotrophic factors. Inappropriate neurotrophic support during brain development could lead to structural disorganisation in which neuronal networks are established in a nonoptimal manner. Inadequate neurotrophic support in adult individuals could ultimately be an underlying mechanism leading to decreased capacity of brain to adaptive changes and increased vulnerability to neurotoxic damage. Brain-derived neurotrophic factor (BDNF) is a mediator involved in neuronal survival and plasticity of dopaminergic, cholinergic, and serotonergic neurons in the central nervous system (CNS). In this review, we summarize findings regarding altered BDNF in schizophrenia and depression and animal models, as well as the effects of antipsychotic and antidepressive treatments on the expression of BDNF. Molecular Psychiatry (2005) 10, 345-352.

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Postmortem studies in mood disorders indicate altered numbers of neurons and glial cells

Cited by 760 publications

References 87 publications

Lower Phosphoinositide 3-Kinase (PI 3-kinase) Activity and Differential Expression Levels of Selective Catalytic and Regulatory PI 3-Kinase Subunit Isoforms in Prefrontal Cortex and Hippocampus of Suicide Subjects

Lower Phosphoinositide 3-Kinase (PI 3-kinase) Activity and Differential Expression Levels of Selective Catalytic and Regulatory PI 3-Kinase Subunit Isoforms in Prefrontal Cortex and Hippocampus of Suicide Subjects

BDNF Serum Concentrations in Healthy Volunteers are Associated with Depression-Related Personality Traits

BDNF in schizophrenia, depression and corresponding animal models

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