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Biomedical subjects

G Wenk

Publications and source records attributed to G Wenk.

14 recordsLinked to original sources

Positron emission tomography in the Rett syndrome: clinical, biochemical and pathological correlates.

A consistent constellation of clinical signs and symptoms define the Rett syndrome, the most prominent of which are disorders of movement and tone. Preliminary pathologic and neurochemical data indicate predominant involvement of the nigrostriatal dopaminergic pathways and the cholinergic system of the basal forebrain region. The age of onset differentiates the Rett syndrome from Alzheimer and Parkinson disease with similar lesions. PET scanning makes it possible to relate the chemistry of the brain to function by measuring the number and affinity of neuroreceptors, metabolism in specific brain regions, and provide important determinants of the underlying mechanisms in disease states.

Adolescent

Basal forebrain cholinergic system: a functional analysis.

This chapter has been organized empirically, focusing on the types of approaches that have been taken to understand BFCS function. This approach reflects the state of our knowledge about the behavioral and psychological functions of the BFCS. Considerable information has been gathered in the very short time that the BFCS has been the object of intense investigation. The results from the neurotoxic lesions and from the HACU studies provide some points of consistency and some puzzling differences. Both approaches to the study of basal forebrain function suggest that the MSA is involved in tasks that require spatial working memory; MSA lesions impaired choice accuracy, and HACU in the HIP was increased after performance. The pattern of results in simpler tasks is more difficult to interpret. In a left-right reference memory discrimination in a T-maze, MSA lesions did not impair acquisition or performance, whereas HACU in the HIP was activated during performance. This pattern of results suggests that although the MSA is engaged during this type of task, its activity is not necessary for normal performance. These, and other comparisons indicate the need for a systematic analysis of task demand (Olton, 1989b). Parametric manipulations of different task demands in a systematic fashion can indicate the extent to which the BFCS is involved in the function associated with each parametric manipulation. Ultimately, of course, the organization of this material should focus on particular psychological functions, rather than the techniques and procedures used to gather the information. Achieving this goal is going to require careful attention to the design of behavioral experiments so that definitive conclusions can be made about the extent to which the BFCS is involved in a given psychological function. A systematic application of task analysis can achieve this goal (Olton, 1986, 1989a, 1989b). For example, BFCS lesions in rats impair choice accuracy in spatial working memory tasks, and performance in these tasks engages the HACU system, at least in the HIP. If the spatial functions of this task involve the BFCS, then a nonspatial version of the task should produce a different pattern of results. If the spatial nature of the task is unimportant for BFCS function, then a nonspatial version of the task should produce the same results. By systematically changing one characteristic of the task at a time, the contribution of each component can be assessed.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine

The Rett syndrome: progress report on studies at the Kennedy Institute.

Clinical, biochemical and pathological studies in patients with the Rett syndrome (RS) are presented. The neuropathological changes and alterations in neurotransmitter markers are particularly interesting and provide valuable information that may be helpful in understanding the behavior and neurological phenotype of RS.

Adolescent

[The effect of iodized mineral substance mixtures for cattle and swine on iodine requirements and struma prevention].

In the southern districts of the GDR the calculated iodine uptake of adults was 80 micrograms/day before the iodine supplementation of the mixtures of mineral substances and the packet kitchen salt. The iodine supplementation of the mixtures of mineral substances for cattle and pig tripled the iodine content of the milk or increased it fivefold in the county of Erfurt and doubled the proportion of iodine of the meat, the inner parts and the sausage produced from them. In a daily consumption of 0.31 of milk and 250 g of meat and sausage a surplus supply of 35 micrograms of iodine for adults was calculated in the southern counties of the GDR. The 35 micrograms of iodine for the future necessary for covering the demand of iodine are certainly delivered by the iodized kitchen salt.

Animal Feed

Long-term behavioral changes in rats following organophosphonate exposure.

The organophosphorus compound soman irreversibly inhibits cholinesterase in both the central and peripheral nervous systems. High doses of this compound produce seizures and death in animals. Surviving animals exhibit neural lesions and behavioral abnormalities. The behavioral effects of a single exposure to soman were evaluated in rats injected with 50 micrograms/kg or 85 micrograms/kg soman or with saline. Each rat was tested for either activity in an open field or performance in a 14 choice point multiple T-maze. All rats were then tested for reactivity to tactile stimuli. Some rats exposed to soman showed increased activity in the open field, learning deficits in the Stone maze, and increased reactivity to tactile stimuli, while others showed behavior similar to that of controls. An increase in reactivity was correlated with increased open field activity and with poor performance in the Stone maze. Rats which had received soman and were abnormal in behavioral tests were more likely to have abnormal brain pathology than rats which had received soman and were normal in behavioral tests.

Animals

Neurotransmitters and memory: role of cholinergic, serotonergic, and noradrenergic systems.

In Alzheimer's disease (AD), pathological changes are found in the basal forebrain cholinergic system (BFCS), serotonergic raphe (RA), and noradrenergic locus coeruleus (LC) systems. The present study was designed to determine the extent to which selective damage in each of these systems individually could produce an impairment of memory, one of the clinical symptoms of AD. Rats were given selective lesions by injecting ibotenic acid into the nucleus basalis magnocellularis and medial septal area (i.e., BFCS); 5,7-dihydroxytryptamine into the medial and dorsal RA; and 6-hydroxydopamine (6-OHDA) into the LC or by ip injections of (2-chloroethyl)N-ethyl-2-bromobenzylamine HCl (DSP4). Levels of choline acetyltransferase (ChAT), norepinephrine, and serotonin verified lesion effectiveness and selectivity. Chronic changes in serotonergic-2 and beta-adrenergic receptors were also determined. Rats were tested in a delayed spatial alternation in a T-maze. BFCS lesions impaired choice accuracy with intertrial delays of 5, 30, and 60 s. RA lesions or DSP4 injections impaired choice accuracy only when the intertrial delay was 60 s. LC lesions (by 6-OHDA) did not impair choice accuracy at any delay. The results suggest that the pathological changes in the BFCS and RA are sufficient to produce the types of memory impairments associated with dementia, but the quantitative effects of pathology in these two systems are different.

Animals

Cholinergic function and memory: extensive inhibition of choline acetyltransferase fails to impair radial maze performance in rats.

The present study investigated the effects of a potent inhibitor of choline acetyltransferase (ChAT), BW813U, on the choice accuracy of rats in the radial arm maze. BW813U (100 mg/kg, IP) produced a rapid (within 1 hour) and substantial decrease in ChAT activity throughout the brain, ranging from 66% (hippocampus) to 80% (caudate nucleus) that lasted up to 5 days. A single injection (50 mg/kg, IP) into rats with lesions (using ibotenic acid) in the nucleus basalis magnocellularis and medial septal area, decreased ChAT activity by 75% and 60% in the cortex and hippocampus, respectively. Lesioned and unlesioned rats were trained on the radial arm maze until they reached a criterion level of performance. Each rat then received an injection of BW813U (50 or 100 mg/kg, IP). Choice accuracy was not impaired at any time following the injection. The lack of effect on performance may be due to 2 possible factors: The radial maze retention paradigm chosen may not be sufficiently difficult, or the decrease in acetylcholine production was not sufficient to affect behavior. Compensation by non-cholinergic neural systems might account for the insensitivity of the rats to significant cholinergic depletion.

Animals

Behavior alters the uptake of [3H]choline into acetylcholinergic neurons of the nucleus basalis magnocellularis and medial septal area.

Behavioral experience changed sodium-dependent high affinity choline uptake (SDHACU) in the hippocampus and frontal cortex. Rats were trained on various behavioral tasks and sacrificed after testing. SDHACU was determined in frontal cortex and hippocampus, areas that receive cholinergic innervation from the nucleus basalis magnocellularis (NBM) and the medial septal area (MSA), respectively. Untrained rats taken directly from their home cages had fairly consistent levels of SDHACU in the hippocampus (1.76 +/- 0.45, X +/- S.E.) and frontal cortex (1.46 +/- 0.37). In the hippocampus of rats performing in a radial maze and T-maze and in rats that surpassed a criterion level in an active avoidance task, SDHACU increased significantly above Cage (untrained) group levels. In the cortex of rats performing the radial maze task, SDHACU decreased slightly. There were no other changes in frontal cortical SDHACU. After behavioral testing ceased, SDHACU in rats performing the radial maze task remained elevated above Control and Treadmill group levels for 20 days, but returned to near control levels 40 days later. Our data demonstrate that a functional differentiation exists between the MSA and NBM cholinergic systems, and that the measurement of SDHACU in central cholinergic neurons is a useful tool to identify the influences of behavior and environment upon changes in neurochemical events and neuronal activity.

Animals

Congenital copper deficiency: copper therapy and dopamine-beta-hydroxylase activity in the mottled (brindled) mouse.

The mottled (Mo) mouse is an animal model of the human congenital copper (Cu) deficiency disorder, Menkes' kinky hair syndrome. Intraperitoneal Cu chloride injections have been shown to produce clinical and morphological improvements in this mutant mouse. Cu injections (10 micrograms/g) on postnatal days 7 and 10 are shown to increase endogenous activity of the Cu-dependent enzyme dopamine-beta-hydroxylase in the brains of Mo mice. The present study provides insight into the long-term neurochemical changes resulting from a possible treatment regimen for Menkes' kinky hair syndrome.

Age Factors

The effect of copper supplementation on the concentration of copper in the brain of the brindled mouse.

The brindled mutant mouse is a useful model to study Menkes kinky-hair syndrome. The metabolic dysfunctions in both human and rodent are related to insufficient levels of bioavailable copper. Recently, copper supplementation therapy has been able both to prevent the appearance of various neuropathological changes and to prolong the life of these mutant mice. The optimum conditions for supplementation have been shown to be two intraperitoneal injections on postnatal days 7 and 10. The present study reports on the brain copper concentrations before, during and after the intraperitoneal copper therapy. The results demonstrate that postnatal days 7 and 10 correspond to two important epochs in copper homoeostasis. The supplementation therapy seems to provide sufficient bioavailable copper to respond to the needs of the animal at these crucial time points. The results are discussed in terms of their importance to the human copper disorder.

Age Factors

Investigations of the performance of a high-performance liquid chromatography system with an electrochemical detector.

A procedure for the determination of norepinephrine and dopamine, based on high-performance liquid chromatography, is evaluated using an electrochemical detector system. The use of an inorganic mobile phase to provide resolution of low retention amines and extend column life is discussed. A high degree of correlation between estimations of endogenous catecholamine levels is reported using both electrochemical and fluorometric detector systems. Inter-assay reproducibility of the extraction method, and sensitivity and linearity of response of the electrochemical detector system are shown to be consistent across trials. The system described is determined to be accurate, sensitive, and reliable over time.

Animals

[A contribution to the generalization of the Gompertz function].

SCHARF (1976) discusses various growth models. For the Gompertz function the differential equation (Formula: see text) is used. In words: the difference between relative growth rate and relative growth acceleration is constant. On the other hand, according to WENK (1973), the differential equation (Formula: see text) applies to the Gompertz function. It can be shown mathematically that (Formula: see text) applies in general. From Eq. (2) one obtains without trouble (Formula: see text). Therefore, the property leading to the Gompertz function may be defined as follows; the logarithmic derivation of the relative growth rate is constant. Eq. (2) is applicable only in special cases. It can be extended by assuming that c is not constant, but a function of time. In this way, a great number of growth functions can be found, which have to be regarded as model-based extensions of the Gompertz function.

Animals