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)

Reductions in 2 neurotransmitter synthesizing enzymes in brain, glutamic acid decarboxylase (GAD) and choline acetyltransferase (CAT), have been found in dementias of different origins, including senile dementia (Alzheimer type). Significant reductions in cerebral GAD have also been found in depression (unipolar). The GAD reductions did not generally appear to be localised in any specific region of the brain examined. However, the reduction of CAT in the hippocampus, relative to reductions in other areas examined, was substantially greater in the brains with Alzheimer-type changes. GAD and CAT activities in normal brains were examined for the effects of some variable factors inherent in necropsy biochemical measurements. These factors included: (i) age; (ii) agonal status; (iii) time of death, and (iv) delay in tissue sampling; and GAD was found to be significantly influenced by (ii), (iii) and (iv) and CAT by (i), (iii) and (iv). None of these factors accounted for the total alterations in the enzyme activities of the mentally abnormal brains. The results indicate that reductions in cerebral GAD require to be interpreted with caution in view of the sensitivity of this enzyme to premortem status but that reductions in cerebral CAT may be a more reliable index of pathological change in senile (Alzheimer-type) dementia.
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PMID:Neurotransmitter enzyme abnormalities in senile dementia. Choline acetyltransferase and glutamic acid decarboxylase activities in necropsy brain tissue. 14 89

Acetyl- and butyryl-cholinesterase activities have been measured biochemically in normal brain tissue, in senile dementia of Alzheimer type and in mental disorders without Alzheimer-type abnormalities. Acetylcholinesterase was significantly reduced and butyrylcholinesterase significantly increased, compared with the normal, in the hippocampus and temporal cortex of the Alzheimer cases. No significant enzyme changes were seen in the other diseases investigated including multi-infarct dementia, schizophrenia and depression. There was no correlation between age and acetylcholinesterase activity, but a significant positive correlation between the butyrylcholinesterase activities with increasing age (60-90 years) was found in the hippocampus. The possible connection between cholinergic system pathology and these cholinesterase abnormalities in Alzheimer dementia is discussed.
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PMID:Changes in brain cholinesterases in senile dementia of Alzheimer type. 70 27

Necropsy brain tissue from normal (control) patients and patients with depression and dementia was examined for activities of various cholinergic components, and these related to the degree of senile plaque formation and extent of intellectual impairment. Choline acetyltransferase and acetylcholinesterase activities decreased significantly as the mean plaque count rose, and in depressed and demented subjects the reduction in choline acetyltransferase activity correlated with the extent of intellectual impairment as measured by a memory information test; muscarinic cholinergic receptor binding activity remained unchanged with increasing senile plaque formation but butyrylcholinesterase activity increased. The results suggest a close relation between changes in the cholinergic system and Alzheimer's dementia, but the precise role of the system in this disease remains to be elucidated.
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PMID:Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. 71 62

The location and number of brain stem serotonin-synthesizing neurons were analyzed in 11 patients with Alzheimer's disease (AD) and 5 age-matched controls using immunohistochemical techniques. In addition, the number of neuritic plaques and neurofibrillary tangles in the cortex and brain stem raphe was evaluated, as was the number of Nissl-stained raphe neurons. AD patients could be classified into two groups based on their raphe pathology; patients with such pathology (AD+) and those without (AD-). The number of large raphe neurons correlated significantly with the number of serotonin-synthesizing neurons in control material, indicating that all large neurons were serotonergic. This relationship was not apparent in AD+ patients, in whom the number of serotonin-synthesizing neurons correlated with the number of neurofibrillary tangles in the raphe of these patients. This indicates that in AD+ patients the serotonin-synthesizing neurons were selectively affected. There was no correlation between raphe and cortical pathology or raphe pathology and patient sex, age, mini-mental score or depression score, even when such scores were weighted for the interval between testing and death. There was a trend for the raphe pathology to correlate with the age of onset and duration of dementia and the Blessed dementia score in AD+ patients. Most AD+ patients with severe raphe lesions had clinical dementia only, while AD- patients had additional clinical features. The raphe lesions were more dramatic in AD+ patients with a rapid progression of symptoms.
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PMID:Brain stem serotonin-synthesizing neurons in Alzheimer's disease: a clinicopathological correlation. 128 56

P300 is a late component of evoked potential which meet special relevance to the study of cognitive processes. P300 indexes categorization processes and the context updating of memory. Its latency reflects the stimulus evaluation time, and P300 amplitude is related to some psychological variables such as expectancy, attention and stimulus significance. In this review, clinical correlation between P300 components and mental diseases are reported, especially dementia, schizophrenia and depression. Delayed P300 latency has been found in Alzheimer disease and in other forms of dementia. Reduced P300 amplitude as well as altered topography has been reported in schizophrenia. In depression, reduced P300 amplitude has been related with longer reaction time. Unfortunately, the diagnosis utility of P300 seems limited. The authors also propose an overview of the actual knowledge on neurobiological findings in the generation of the P300 wave. Anatomical data point out the importance of the limbic system, more specifically, of the hippocampus and the locus coeruleus, in generating and modulating P300 wave. Data from the literature on the psychopharmacological modifications induced by cholinergic, catecholaminergic and other agents, are reviewed. Although the dopaminergic and noradrenergic systems are of some importance, these data emphasise the importance of the cholinergic system for the generation and modulation of P300 amplitude and latency. The value and interpretation of these neurobiological and clinical findings are discussed.
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PMID:[P 300 slow potential. Clinical interest in 3 mental diseases and neurobiology: a review]. 129 92

Based on comparative clinical and morphometric studies in 45 autopsy cases of Parkinson's disease (PD), 27 clinically presenting with akinesia and rigidity (AR-type), 18 with predominant resting tremor (T-type), the neurobiological basis of the major clinical subtypes in PD is discussed. The AR-type showed higher neuronal losses in locus coeruleus (LC) and in medial and lateral parts of substantia nigra (SNM, SNL), suggesting lesion patterns different from the T-type. More severe cell loss in the serotonergic dorsal raphe nucleus was observed in PD patients with depression than in non-depressed ones. Demented PD subjects showed higher cell loss in SNM than non-demented ones indicating dysfunction of the mesocortical dopamine system, and significantly more severe Alzheimer lesions in isocortex and hippocampus. These and other recent data from the literature indicate that some major clinical features of PD are related to lesions of distinct neuronal systems.
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PMID:Clinico-pathological correlations in Parkinson's disease. 132 May 31

The peculiar tyramine uptake inhibitory effect of (-)deprenyl prompted structure-activity relationship studies aiming to develop new spectrum central nervous system stimulants which are devoid of MAO inhibitory potency and operate de facto as indirectly acting, nonreleasing sympathomimetics. Of the derivatives synthesized for this purpose, 1-phenyl-2-propylaminopentane (PPAP) was selected as the reference substance and its pharmacological spectrum is presented. PPAP is taken up by the catecholamine axon terminal membrane and the vesicular membrane but it is devoid of catecholamine-releasing property. As a result, PPAP is, by interference, a potent inhibitor of the uptake of indirectly acting sympathomimetic releasers and of the catecholamine transmitters. This was proved, on the one hand, by measuring the uptake of [14C]PPAP into the catecholaminergic axon terminals and the inhibition of the uptake of [3H]noradrenaline and [3H]dopamine by PPAP in the rat brain, and, on the other hand, on the pulmonary artery strip of the rabbit and, in vivo, using the rat nictitating membrane as a detector. PPAP increases motility at 2 mg/kg and, in contrast to amphetamine, inhibits it at very high doses (50 mg/kg) only. A two-sided antagonism in the motility-increasing effect between PPAP and amphetamine and, more pronounced, between PPAP and mazindol was detected. PPAP is substantially less effective in inducing stereotyped behavior than either amphetamine or methamphetamine. PPAP facilitates learning and retention, is highly potent in antagonizing the tetrabenazine-induced depression in behavioral tests and is very effective in the forced swimming test. Whereas amphetamines facilitate performance in a very narrow range of low doses, which turns, at a modest elevation of the dose, into the opposite effect, PPAP improves performance within a reasonably broad dose range. Based on the peculiar pharmacological profile of PPAP, its potential usefulness in depression, in Alzheimer's disease and in attention-deficit-hyperkinetic disorder seems to be plausible.
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PMID:The pharmacology of 1-phenyl-2-propylamino-pentane (PPAP), a deprenyl-derived new spectrum psychostimulant. 135 24

Somatostatin (somatotropin release-inhibiting factor, SRIF) was originally discovered (1) during the purification of growth hormone-releasing factor from rat hypothalamus and was subsequently isolated and characterized (2) in 1972 from ovine hypothalamus. Since its initial characterization, SRIF has been shown to fulfill criteria for a neurotransmitter and to directly modulate neuronal activity as well as acting as an inhibitory factor regulating endocrine and exocrine secretion. Alterations in cerebrospinal fluid (CSF) concentrations of SRIF have been reported in several diseases exhibiting prominent cognitive dysfunction, including Alzheimer's disease (AD), major depression, Huntington's chorea, multiple sclerosis, schizophrenia and Parkinson's disease, while evidence for regional brain tissue concentration deficits in SRIF are more specific for AD. This mini-review will focus on the studies reporting alterations in CSF and postmortem tissue concentrations of SRIF in AD and depression.
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PMID:Somatostatin in Alzheimer's disease and depression. 135 21

6R-L-erythro-5, 6, 7, 8-Tetrahydrobiopterin (6R-BH4) is known as a cofactor for the hydroxylases of phenylalanine, tyrosine and tryptophan and also as a cofactor for nitric oxide synthase. Recently, a novel function of 6R-BH4 has been found: that is, 6R-BH4 acts on specific membrane receptors to directly stimulate the release of monamine neurotransmitters such as dopamine and serotonin, independently of its cofactor activity. In addition, it indirectly stimulates the release of non-monoamine neurotransmitters such as acetylcholine and glutamate, through activation of monoaminergic systems. In this paper, we briefly review recent experimental data, which provide new insights into the role of 6R-BH4 as a regulator of neuronal function. We also discuss the possibility of treatment by 6R-BH4 of neuropsychiatric diseases such as Parkinson's disease, Alzheimer's disease, depression and infantile autism.
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PMID:[A novel function of tetrahydrobiopterin]. 136 Nov 76

Assessment and treatment of behavior problems in patients with Alzheimer disease and related disorders is a seriously neglected area of study. Despite the fact that such problems are integral to the disorder, little is known about effective management. This article summarizes the current thinking on five areas of prime importance to patients, care providers, and health care professionals: agitation, assault/aggression, screaming, wandering, and depression/apathy/withdrawal. Methodological guidelines for studying these disorders are provided. Emphasis is on recognizing that behavior problems are important areas of study in their own right as well as in conjunction with studies of cognition.
Alzheimer Dis Assoc Disord 1992
PMID:Management of behavior disturbance in Alzheimer disease: current knowledge and future directions. 138 83


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