Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

S100 beta, a calcium binding brain protein expressed by astrocytes, has been shown to be involved in higher neural processes, including hippocampal-dependent behavioral traits and hippocampal neuronal long-term potentiation (LTP) and depression (LTD), neurophysiological phenomena that may be involved in exploring, learning and remembering novel stimuli. In the present study, the exploratory behavior of previously generated transgenic mice overexpressing the protein are compared to that of normal control mice of identical genetic background and age in a T-maze. The test mice encountered a normal control and an S100 beta transgenic mouse (the choice mice) in the goal arms of the T-maze. We show that no test mice exhibited any preference for either genotype of choice mouse. However, there was a significant difference in the spatial and temporal exploratory pattern between control and S100 beta test mice, demonstrating that S100 beta overexpression significantly altered the behavior of the transgenic mice. We suggest that one probable factor underlying the abnormalities observed is impaired short-term memory.
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PMID:Conspecific exploration in the T-maze: abnormalities in S100 beta transgenic mice. 880 39

S100 beta, a calcium binding astrocytic brain protein, influences hippocampal long-term potentiation (LTP) and depression (LTD), synaptic processes suggested to play role in spatial (contextual) learning and memory. In the present study we trained S100 beta transgenic and wild-type control mice in a nonspatial version of the Morris water maze, the visible platform task, and analyzed retention of memory over periods of 18 h, several days, and weeks. The results show that acquisition and retention were not altered in the S100 beta transgenic mice compared to control. However, a single alteration of an environmental stimulus, water temperature, significantly worsened the performance of transgenic mice. This impairment lasted for two consecutive trials separated by a 2-week intertrial interval, suggesting a temporary disturbance associated with memory processes. We discuss the possibility that these results are compatible with normal cortical but abnormal hippocampal functioning in the S100 beta transgenic mice.
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PMID:Memory and the effect of cold shock in the water maze in S100 beta transgenic mice. 884 Sep 25

Recent evidence suggests that slowly propagating Ca2+ waves from astrocytes can modulate the function of neurons. Altering astrocytic calcium processes in vivo may therefore affect neuronal and behavioral phenotypes. Previously, we generated transgenic mice that overexpress an astrocytic calcium-binding protein, S100 beta. Immunocytochemistry and in situ hybridization showed elevated expression in the astrocytes of the hippocampus and other brain regions. Neurons in the hippocampus were negative for S100 beta. In this paper we analyze the hippocampal electrophysiology and learning properties of mice from two transgenic lines. Significant differences were found between the hippocampal slices of normal and transgenic mice in their response to high frequency (100 Hz) stimulation. The overall distribution of post-tetanic excitatory postsynaptic potentials (EPSP) of the slices from the transgenic mice was shifted significantly toward smaller values to a degree that 25% of slices exhibited depression. The altered hippocampal neurophysiology was accompanied by an impairment in a hippocampal-dependent learning task. Transgenic mice showed significant impairment in a spatial version of the Morris water maze, however, they performed normally in non-spatial tasks. Probe trials showed that transgenic mice, though significantly impaired, also acquired spatial information. The results suggested that the impairment was not due to motor dysfunction, impaired vision or motivation of the transgenic mice, findings compatible with a possible hippocampal mechanism. We conclude that overexpression of S100 beta in astrocytes impairs, but does not abolish, the ability to solve a spatial task, and it leads to a significantly decreased post-tetanic potentiation in the hippocampal slice. We hypothesize that the changes are due to calcium mediated processes. Our results support the notion that astrocytes are involved in higher brain functions.
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PMID:Overexpression of a calcium-binding protein, S100 beta, in astrocytes alters synaptic plasticity and impairs spatial learning in transgenic mice. 1046 64

Previous studies have reported alterations of glial cells and particularly astrocytes in mood disorders. Therefore, serum concentration of the astrocytic marker S100B was ascertained with an immunoluminometric assay in 20 patients with mood disorder and 12 healthy age-matched controls. Serum S100B was elevated in major depression (median after admission 410 ng/l, at discharge < 100 ng/l) and mania (130, 160 ng/l), when compared with controls (< 100 ng/l; rho< 0.01). Antidepressive treatment reduced S100B in conjunction with severity of depressive symptoms ( rho< 0.01). The severity of depression (Hamilton Depression Rating Scale) was positively correlated with S100B (r(s) = 0.51, rho< 0.005). Elevated serum S100B during depressive and manic episodes of mood disorders may indicate alterations of astrocytes, which are reversed by antidepressive treatment.
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PMID:S100B is increased in mood disorders and may be reduced by antidepressive treatment. 1235 25

Selective attention processes (N2 and P3 components of event-related potentials (ERPs)) have been shown to be impaired in depressed patients but findings have been mixed. Part of this variability might be explained by neurobiological factors. ERPs (Go/Nogo paradigm) were investigated in patients with remitted major depression in relation to S100B. S100B, an astroglial protein with neuroplastic properties, has been shown to be increased in depression. Its pathophysiologic role in depression, however, is not yet sufficiently understood. Patients with increased S100B serum levels (n=6) showed a normal N2- and P3-amplitude in contrast to a reduced N2- and P3-amplitude in patients with normal S100B serum levels (n=6). These findings provide evidence of a correlation between S100B levels and attentional processes in patients with recurrent depression and further substantiate S100B's role as a marker in the course of affective disorders.
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PMID:Target evaluation processing and serum levels of nerve tissue protein S100B in patients with remitted major depression. 1469 84

The S100B is a Ca2+ binding proteins of EF-hand type and is produced primarily by astrocytes in the central nervous system. This protein has been implicated in the Ca2+-dependent regulation of a variety of intracellular functions such as protein phosphorylation, enzyme activities, cell proliferation and differentiation, dynamics of cytoskeleton constituents, structural organization of membranes, intracellular Ca2+ homeostasis, inflammation, and protection from oxidative cell damage. Recent studies suggest that released S100B exerts paracrine and autocrine effects on neurons and glia. On the other hand, elevations of S100B levels in blood or cerebrospinal fluid have been observed in patients with Alzheimer's disease, Down's syndrome, amyotrophic lateral sclerosis, multiple sclerosis, schizophrenia, depression, cerebral stroke and traumatic brain injury, and the levels have reached micromol/L-order at focal regions. It has been documented that the excessive S100B promotes the expression of inducible nitric oxide synthase or pro-inflammatory cytokines and exhibits detrimental effects on neurons. On studies using some animal models of the cerebral stroke or Alzheimer's disease, it is suggested that the excessive S100B produced by activated astrocytes precedes neurodegenerations. Authors discussed the relationship between neurological disorders and the S100B.
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PMID:[S100B: astrocyte specific protein]. 1663 91

Occasionally, multiple names are given to the same gene/protein. When this happens, different names can be used in subsequent publications, for example in different research areas, sometimes with little or no awareness that the same entity known under a different name may have a major role in another field of science. Recent reports about the protein p11 presented findings that this protein, commonly known as S100A10, may play a crucial role in depression and antidepressant treatment mechanisms. One set of data showed an increased expression of this protein in the brain of mice treated with antidepressants. P11/S100A10 is only one of several S100 proteins expressed in the brain. Interestingly, it has been previously noted that antidepressant treatment increases the brain content of another S100 protein, S100B. It appears that up-regulating the brain content of various S100 proteins might be a common feature of antidepressants. In cells coexpressing S100A10 and S100B, these proteins may interact and exert opposite regulatory roles. Nevertheless, S100A10 is predominantly expressed in certain types of neurons whereas S100B is more abundant in glia. Thus, an interplay among multiple members of the S100 proteins might be important in determining the region and cell specificity of antidepressant mechanisms. Calling the p11 protein by its other name, S100A10, may prompt more investigators from different fields to participate in this new direction of neurobiological research.
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PMID:Nomen est Omen: do antidepressants increase p11 or S100A10? 1672 32

Arundic acid (ONO-2506) is believed to be neuroprotective because of its actions on glia cells; i.e., its inhibitory effects on the synthesis of a calcium-binding protein S100B. ONO-2506 is undergoing clinical trials for the treatment of patients with stroke and Alzheimer's disease. Recent clinical studies point to a pervasive comorbidity of depression with stroke and Alzheimer's disease. Previously, S100B has been implicated in the pathobiological mechanisms of depression. Preclinical studies have shown that antidepressant treatment significantly increases brain S100B. Here we hypothesize that available data that link S100B with depression, along with the proposed inhibitory action of ONO-2506 on S100B synthesis, indicate that this compound could increase vulnerability for depression in patients at risk for this disorder, and we propose that evaluation of patients with stroke and Alzheimer's disease for the presence of depression should be routine in clinical trials employing ONO-2506. Although it may be open for discussion whether the neuroprotective effects of ONO-2506 are exclusively due to its inhibition of S100B synthesis, the latter action of ONO-2506 warrants studies of the effects of this drug in the pathobiology of depression.
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PMID:Could treatment with arundic acid (ONO-2506) increase vulnerability for depression? 1679 59

Bipolar disorder (BD) is a chronic, severe, and highly disabling psychiatric disorder; peripheral markers have been used to assess biochemical alterations associated with BD and/or possibly involved in its pathophysiology. Beyond neuronal commitment, many groups have proposed the involvement of glial activity in psychiatric disorders. Other biochemical markers, particularly associated with oxidative stress, have been studied in BD. In the present study, we evaluated glial involvement and oxidative stress in patients with BD. Glial activity was assessed by measuring serum S100B content; oxidative stress was assessed using serum thiobarbituric acid reactive substances (TBARS) and activities of antioxidant enzymes in BD patients during different episodes of disease. We found a significant increment of serum S100B during episodes of mania and depression, but not in euthymic patients. Superoxide dismutase (SOD) activity, as well the SOD/glutathione peroxidase plus catalase ratio, was also increased in manic and depressed patients. On the other hand, TBARS levels were increased in BD patients regardless of the phase of the disorder. These findings suggest a potential oxidative damage in BD patients. This peripheral oxidative imbalance indicates that systemic changes are taking place during the active phases of the illness. Such changes appear to relate to astrocyte function, as indicated by serum S100B elevation.
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PMID:Serum S100B and antioxidant enzymes in bipolar patients. 1695 21

Hippocampus is the brain structure, vital for episodic and declarative memory. Atrophy of the human hippocampus is seen in a variety of psychiatric and neurological disorders e.g. recurrent depression, schizophrenia, bipolar disorder, post-traumatic stress disorder, epilepsy, head injury, and Alzheimer's disease (AD). Importantly, aging hippocampus also undergoes atrophy. In many instances, for example, AD, the atrophy precedes the development of symptoms while in others, there is a temporal relationship between atrophy and symptomatology. The presence of atrophied hippocampus is one of the most consistent features of many common psychiatric disorders. Several factors contribute to this atrophy. Stress is one of the most profound factors implicated and the mechanisms involve glucocorticoids, serotonin, excitatory amino acids etc. Hippocampal formation as a whole can undergo atrophy or its individual structural components e.g. apical dendrities can exhibit atrophy. Several drugs of unrelated classes have been shown to prevent atrophy indicating heterogenous manner in which hippocampal atrophy is produced. These include, tianeptine (affects structural plasticity in hippocampus and is an effective antidepressant); phenytoin (antiseizure and neuroprotective); fluoxetine (downregulates neurodegenerative enzyme and increases neuroprotective hippocampal S100 beta); lithium (neuroprotective and antiapoptotic); tricyclic antidepressants (increase hippocampal neurogenesis); antipsychotics (reduce hippocampal neuronal suppression); sodium valproate (increases neurogenesis) and mifepristone (antioxidant, neuroprotective and anti-glucocorticoid). Now the most important question is: to what extent does the hippocampal atrophy play a role in the genesis of symptoms of diseases or their progression? And if it does, can we achieve the same degree of prevention or reversal seen in experimental animals, in humans also. An even more important question is: whether the prevention of atrophy would be clinically useful in affecting disease, viz slowing its progression, reducing morbidity, complications or positively affecting the outcome of one or more of its clinically important aspects. If the answer to this is yes, we would have to know at what stage of the disease we use the drugs, dose, duration, follow-up and efficacy. The use of these drugs in the above mentioned conditions can not only test the potential of atrophy as a future drug target, but could also help in learning more about the hippocampus in both health and diseases.
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PMID:Is hippocampal atrophy a future drug target? 1828 54


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