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

Transthyretin (TTR) is a beta-sheet rich protein whose plasma half life is 1.9 days. It behaves as a tetramer and binds to retinol binding protein (RBP) and thyroxin in plasma. Since TTR is a tryptophan-rich-protein, the protein is used as a useful marker protein for nutrition supporting team (NST). However, TTR is also an anti-acute phase protein, and the concentration is influenced by various conditions, such as inflammation and infection, Mutated forms of TTR are the precursor protein of familial amyloidotic polyneuropathy (FAP). Since plasma TTR is predominantly synthesized by the liver, liver transplantation has been performed as an effective therapy for FAP. Recent research revealed that TTR plays important roles in various central nervous system disorders, such as Alzheimer disease, depression, and lead intoxication. To elucidate the pathogenesis of those disorders, an accurate measurement of TTR concentrations in plasma and cerebrospinal fluids is of vital importance.
 ...
PMID:[Immunological and serological laboratory tests: transthyretin]. 1602 84

There is an enormous initiative to establish the genetic basis for disorders of brain function. Unfortunately, genetic intervention is not accomplished easily in the nervous system. One strategy is to engineer and deliver to neurons specialized viral vectors that carry a gene (or genes) of interest, thereby exploiting the natural ability of viruses to insert genetic material into cells. When delivered to brain cells, these vectors cause infected cells to increase the expression of the genes of interest. The ability to deliver genes into neurons in vitro and in vivo with herpes simplex virus (HSV) amplicon vectors has made it possible to carry out exactly these sorts of experiments. This technology has the potential to offer new insights into the etiology of a wide variety of neuropsychiatric disorders. We describe the use of HSV amplicon vectors to study Alzheimer disease, drug addiction, and depression, and discuss the considerations that enter into the use of these vectors both in vitro and in vivo. The HSV amplicon virus is a user-friendly vector for the delivery of genes into neurons that has come of age for the study of brain function.
 ...
PMID:Use of herpes virus amplicon vectors to study brain disorders. 1620 10

We review here aggression-related human psychopathologies and propose that human aggressiveness is mainly due to three major factors: (i) brain dysfunction affecting aggression-controlling brain centers (e.g. in certain types of brain lesions, epilepsy, Alzheimer disease, etc.); (ii) hypoarousal associated with chronically low plasma glucocorticoids, which foster violence by diminishing emotional barriers that limit such behaviors (e.g. in conduct disorder and antisocial personality disorder); (iii) hyperarousal which leads to irritability and outbursts (e.g. in depression, intermittent explosive disorder, chronic fatigue, etc.). Different disorders are associated with different types of aggressiveness; e.g. hypoarousal is often associated with instrumental aggression, whereas hyperarousal is associated with uncontrollable outbursts. Many psychological disorders have been simulated in laboratory models, which were used to assess aggressiveness. Little effort was invested, however, in assessing the abnormal dimension of such aggressiveness. We present here three models that appear especially suitable to assess abnormal aspects of rodent aggression: (i) abnormal attack targeting (head, throat, and belly) that is induced by hypoarousal in rats and models violence in hypoarousal-driven human aggression (ii) 'escalated' aggression (increased aggressive response due to frustration or instigation), which models irritability and hyperarousal-driven aggressiveness; and (iii) context-independent attacks induced by hypothalamic stimulation or genetic manipulations. These three models address different aspects of abnormal aggressiveness, and can become extremely useful in three areas: in evaluating and assessing models of human psychopathologies, in studying transgenic animals, and in developing new treatment strategies. Research based on these or similar models do not address aggressiveness in quantitative terms, but follows the development of abnormal aspects, and the possibilities of their specific treatment.
 ...
PMID:Normal and abnormal aggression: human disorders and novel laboratory models. 1648 89

It is widely thought that Alzheimer's disease (AD) begins as a malfunction of synapses, eventually leading to cognitive impairment and dementia. Homeostatic synaptic scaling is a mechanism that could be crucial at the onset of AD but has not been examined experimentally. In this process, the synaptic strength of a neuron is modified so that the overall excitability of the cell is maintained. Here, we investigate whether synaptic scaling mediated by l-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) contributes to pathology in double knockin (2 x KI) mice carrying human mutations in the genes for amyloid precursor protein and presenilin-1. By using whole-cell recordings, we show that 2 x KI mice exhibit age-related downscaling of AMPAR-mediated evoked currents and spontaneous, miniature currents. Electron microscopic analysis further corroborates the synaptic AMPAR decrease. Additionally, 2 x KI mice show age-related deficits in bidirectional plasticity (long-term potentiation and long-term depression) and memory flexibility. These results suggest that AMPARs are important synaptic targets for AD and provide evidence that cognitive impairment may involve downscaling of postsynaptic AMPAR function.
 ...
PMID:AMPA receptor downscaling at the onset of Alzheimer's disease pathology in double knockin mice. 1649 45

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a rare autosomal dominant disorder characterized by cerebral white matter degeneration with axonal spheroids leading to progressive cognitive and motor dysfunction. We report clinical and pathological features, as well as molecular genetic analysis, of a family with HDLS. A pedigree consisting of 27 persons in 5 generations contained 6 affected individuals. Dementia and depression were common; two individuals presented with a syndrome resembling corticobasal degeneration (CBD). Postmortem neuropathologic evaluation of three affected individuals revealed enlargement of the lateral ventricles and marked attenuation of cerebral white matter, but preservation of white matter in brainstem and cerebellum, except for the corticospinal tract. Histopathologic studies showed a loss of myelinated fibers, lipid-laden macrophages and bizarre astrocytes, as well as abundant axonal spheroids that were immunoreactive for phosphorylated neurofilament protein and amyloid precursor protein (APP), but not alphaB-crystallin and variably with ubiquitin. By electron microscopy, axonal spheroids contained aggregates of intermediate filaments or of organelles that were predominantly vesicular and lamellar. The cerebral cortex had focal neuronal degeneration with alphaB-crystallin-immunoreactive ballooned neurons. In summary, the present report describes a previously unreported kindred with HDLS with individuals presenting as CBD. Immunohistochemistry for APP and alphaB-crystallin demonstrates distinctive neurodegeneration in cerebral axons and perikarya.
 ...
PMID:Hereditary diffuse leukoencephalopathy with spheroids: clinical, pathologic and genetic studies of a new kindred. 1652 41

The objective of this update is to give an overview of the effects of dietary nutrients on the structure and certain functions of the brain. As any other organ, the brain is elaborated from substances present in the diet (sometimes exclusively, for vitamins, minerals, essential amino-acids and essential fatty acids, including omega- 3 polyunsaturated fatty acids). However, for long it was not fully accepted that food can have an influence on brain structure, and thus on its function, including cognitive and intellectuals. In fact, most micronutrients (vitamins and trace-elements) have been directly evaluated in the setting of cerebral functioning. For instance, to produce energy, the use of glucose by nervous tissue implies the presence of vitamin B1; this vitamin modulates cognitive performance, especially in the elderly. Vitamin B9 preserves brain during its development and memory during ageing. Vitamin B6 is likely to benefit in treating premenstrual depression. Vitamins B6 and B12, among others, are directly involved in the synthesis of some neurotransmitters. Vitamin B12 delays the onset of signs of dementia (and blood abnormalities), provided it is administered in a precise clinical timing window, before the onset of the first symptoms. Supplementation with cobalamin improves cerebral and cognitive functions in the elderly; it frequently improves the functioning of factors related to the frontal lobe, as well as the language function of those with cognitive disorders. Adolescents who have a borderline level of vitamin B12 develop signs of cognitive changes. In the brain, the nerve endings contain the highest concentrations of vitamin C in the human body (after the suprarenal glands). Vitamin D (or certain of its analogues) could be of interest in the prevention of various aspects of neurodegenerative or neuroimmune diseases. Among the various vitamin E components (tocopherols and tocotrienols), only alpha-tocopherol is actively uptaken by the brain and is directly involved in nervous membranes protection. Even vitamin K has been involved in nervous tissue biochemistry. Iron is necessary to ensure oxygenation and to produce energy in the cerebral parenchyma (via cytochrome oxidase), and for the synthesis of neurotransmitters and myelin; iron deficiency is found in children with attention-deficit/hyperactivity disorder. Iron concentrations in the umbilical artery are critical during the development of the foetus, and in relation with the IQ in the child; infantile anaemia with its associated iron deficiency is linked to perturbation of the development of cognitive functions. Iron deficiency anaemia is common, particularly in women, and is associated, for instance, with apathy, depression and rapid fatigue when exercising. Lithium importance, at least in psychiatry, is known for a long time. Magnesium plays important roles in all the major metabolisms: in oxidation-reduction and in ionic regulation, among others. Zinc participates among others in the perception of taste. An unbalanced copper metabolism homeostasis (due to dietary deficiency) could be linked to Alzheimer disease. The iodine provided by the thyroid hormone ensures the energy metabolism of the cerebral cells; the dietary reduction of iodine during pregnancy induces severe cerebral dysfunction, actually leading to cretinism. Among many mechanisms, manganese, copper, and zinc participate in enzymatic mechanisms that protect against free radicals, toxic derivatives of oxygen. More specifically, the full genetic potential of the child for physical growth ad mental development may be compromised due to deficiency (even subclinical) of micronutrients. Children and adolescents with poor nutritional status are exposed to alterations of mental and behavioural functions that can be corrected by dietary measures, but only to certain extend. Indeed, nutrient composition and meal pattern can exert either immediate or long-term effects, beneficial or adverse. Brain diseases during aging can also be due to failure for protective mechanism, due to dietary deficiencies, for instance in anti-oxidants and nutrients (trace elements, vitamins, non essential micronutrients such as polyphenols) related with protection against free radicals. Macronutrients are presented in the accompanying paper.
 ...
PMID:Effects of nutrients (in food) on the structure and function of the nervous system: update on dietary requirements for brain. Part 1: micronutrients. 1706 9

Effects of concurrent intracerebroventricular administration of amyloid-beta peptide 25-35 (Abeta(25-35)) and the proinflammatory cytokine tumor necrosis factor-alpha (TNFalpha) to rats were investigated. A battery of behavioral tests including radial arm maze, passive avoidance, elevated plus-maze and forced swim test as well as histological methods were used. A single administration of Abeta(25-35) induced delayed behavioral deficits manifested in reference and working memory disturbances in the radial maze task involving spatial memory. However, no effects of Abeta(25-35) on learning or retention in a passive avoidance test could be revealed. Abeta(25-35) appeared to decrease anxiety without affecting depression-like behavior in the rats. Abeta(25-35)-induced cognitive deficits could be related to the moderate neuronal cell loss found in the hippocampal CA1 field. Though administration of TNFalpha did not impair learning and memory of rats in the radial maze, it induced gross changes in their behavior during passive avoidance training. Though TNFalpha did not protect against Abeta(25-35)-induced neuronal cell loss in the CA1 field of hippocampus, co-administration of TNFalpha with Abeta(25-35) resulted in an improvement of reference memory impaired by the amyloid peptide, but not of working memory.
 ...
PMID:Differential effects of tumor necrosis factor-alpha co-administered with amyloid beta-peptide (25-35) on memory function and hippocampal damage in rat. 1707 Jun 5

Neurosteroids play a significant role in neurodevelopment and are involved in a wide variety of psychopathological processes. There is accumulating evidence on their role in adult psychopathology, including Alzheimer disease, schizophrenia, mood disorder, anxiety disorders and post-traumatic stress disorder. Little is known, however, about the possible role of neurosteroids in child and adolescent psychopathology although there is increasing evidence for their critical role from the early stages of brain development until adolescence. In this review we focus on the involvement of neurosteroids in neurodevelopment and mental disorders in children and adolescents. Adequate physiological levels protect the developing neural system from insult and contribute to the regulation of brain organization and function. Neurosteroids may be involved in the pathophysiology and pharmacotherapy of a variety of disorders in children and adolescents, including schizophrenia, depression, eating disorders, aggressive behavior and attention deficit. The complex interaction between neurosteroids, neurodevelopment, life-events, genetics and mental disorders in children and adolescents merits further investigation.
 ...
PMID:Neurosteroids in child and adolescent psychopathology. 1707 19

Beta amyloid (Abeta), a peptide generated from the amyloid precursor protein (APP) by neurons, is widely believed to underlie the pathophysiology of Alzheimer's disease. Recent studies indicate that this peptide can drive loss of surface AMPA and NMDA type glutamate receptors. We now show that Abeta employs signaling pathways of long-term depression (LTD) to drive endocytosis of synaptic AMPA receptors. Synaptic removal of AMPA receptors is necessary and sufficient to produce loss of dendritic spines and synaptic NMDA responses. Our studies indicate the central role played by AMPA receptor trafficking in Abeta-induced modification of synaptic structure and function.
 ...
PMID:AMPAR removal underlies Abeta-induced synaptic depression and dendritic spine loss. 1714 4

Overexpression of the amyloid precursor protein (APP) in hippocampal neurons leads to elevated beta-amyloid peptide (Abeta) production and consequent depression of excitatory transmission. The precise mechanisms underlying APP-induced synaptic depression are poorly understood. Uncovering these mechanisms could provide insight into how neuronal function is compromised before cell death during the early stages of Alzheimer's disease. Here we verify that APP up-regulation leads to depression of transmission in cultured hippocampal autapses; and we perform whole-cell recording, FM imaging, and immunocytochemistry to identify the specific mechanisms accounting for this depression. We find that APP overexpression leads to postsynaptic silencing through a selective reduction of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated currents. This effect is likely mediated by Abeta because expression of mutant APP incapable of producing Abeta did not depress transmission. In addition, although we eliminate presynaptic silencing as a mechanism underlying APP-mediated inhibition of transmission, we did observe an Abeta-induced presynaptic deficit in vesicle recycling with sustained stimulation. These findings demonstrate that APP elevation disrupts both presynaptic and postsynaptic compartments.
 ...
PMID:Amyloid precursor protein overexpression depresses excitatory transmission through both presynaptic and postsynaptic mechanisms. 1718 15


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>