Cholinergic septal grafts into the hippocampal formation improve spatial learning and memory in aged rats by an atropine-sensitive mechanism

Behaviorally impaired old rats were selected from a population of 75 21- to 23-month-old rats on the basis of the place-investigated abilities in the Morris' water-maze task. After the pretransplant test, half of the old impaired rats received bilateral intrahippocampal cell suspension grafts prepared from the fetal septal-diagonal band region, which is rich in developing cholinergic neurons; the other half were left as sham-operated controls. Twelve weeks after grafting, the rats were retested in the water-maze using alternating cue-navigation and place-navigation trials (i.e., with visible or nonvisible escape platform). While the old impaired controls had deteriorated further between the 2 tests and showed poor retention of the pretransplant performance level, the grafted rats were significantly improved in comparison with both their pretransplant performance and the performance of the old impaired controls in the posttransplant test. The graft-induced effect was due both to an improved retention of the performance level acquired in the test performed prior to transplantation surgery, and to an improved acquisition of spatial memory of the escape platform site during the posttransplant test week (measured as an improved focusing of search over the platform site after platform removal). The acetylcholine esterase inhibitor physostigmine had no or only marginal effects on the performance of any of the young or aged rat groups. By contrast, the recovered navigational abilities and spatial memory in the grafted animals were completely abolished after administration of the muscarinic receptor antagonist atropine. A similar atropine-sensitivity was seen in behaviorally nonimpaired aged rats but not in the well-trained young control rats. The results show that cholinergic septal grafts, implanted into the hippocampal formation, improved spatial learning in the impaired aged rats primarily, or perhaps exclusively, by a recovery of the rats' ability to use spatial cues for place-navigation in the water-maze, while other aspects of the performance deficits in the water-maze task in the aged rats were left unaffected by the septal grafts. On the basis of parallel morphological studies, it is proposed that the effects of the septal grafts on the spatial learning impairments in the aged rats are critically dependent on the direct action of cholinergic neurons in the grafts via synapses formed onto neuronal elements in the host by their ingrowing axons.     

Examining the dynamics of spouse abuse: an alternative view

Spouse abuse continues to be a great problem in our society. Much of the literature about the problem, however, assumes that the roles of perpetrator and victim are always fixed, with the man as perpetrator and the woman as victim. This perception is understandable if the injuries received are the focus of attention, and the sole informant about the violence is the person who has most often been the recipient of injuries. On occasions when both partners are interviewed, a different perception of violent relationships is likely to emerge. Violence can be viewed as occurring along a continuum. One extreme is represented as mutual combat, in which both partners play a role in the escalation of conflict. The other extreme follows the traditional concept of battering where the woman is victimized by the man. Primary care practitioners are in a position to assist clients who are in violent relationships and to help them learn more functional problem-solving skills. This article focuses on methods of identifying violent couples and teaching them how to interrupt the cycle of violence.     

Urinary medium-chain acylcarnitines in medium-chain acyl-CoA dehydrogenase deficiency, medium-chain triglyceride feeding and valproic acid therapy: sensitivity and specificity of the radioisotopic exchange/high performance liquid chromatography method.

To determine the sensitivity and specificity of detecting urinary medium-chain acylcarnitines for the diagnosis of MCAD deficiency, 114 urine specimens from 75 children with metabolic diseases and controls were analyzed in a blinded fashion using a radioisotopic exchange/HPLC method. All 47 patients with MCAD deficiency were correctly diagnosed using the criterion hexanoylcarnitine or octanoylcarnitine peak areas larger than those of other medium-chain acylcarnitines. The majority of them were tested during the asymptomatic state without L-carnitine loading. Four patients with other defects of fatty acid oxidation and three patients receiving valproic acid had a similar acylcarnitine excretion pattern. To further examine the specificity of the method, eight infants receiving a diet enriched with medium-chain triglycerides and 13 additional patients receiving valproic acid were studied. Most of these also tested positive for MCAD deficiency by the above criterion. Analysis by a new gas chromatographic-mass spectrometric procedure revealed that octanoylcarnitine, not valproylcarnitine, was the most abundant medium-chain carnitine ester excreted by a patient treated with valproic acid. Quantitation of urinary hexanoylcarnitine and octanoylcarnitine showed considerable overlap among patients with MCAD deficiency and those receiving valproic acid or a medium-chain triglyceride-enriched diet. MCAD deficiency can be reliably detected in urine specimens by this method without the need for prior carnitine loading. However, other defects in fatty acid oxidation must be differentiated from MCAD deficiency, and a history of medium-chain triglyceride or valproic acid administration must be considered if the diagnosis of MCAD deficiency is sought through analysis of urinary acylcarnitines.     

Effects of butanedione monoxime on neuromuscular transmission.

1. The amplitude of endplate potentials was increased by concentrations of butanedione monoxime (BDM, 5-20 mM) that typically caused muscle paralysis. 2. Although BDM slowed the decay of spontaneous miniature endplate currents, the effect was insufficient to explain most of the large increase in amplitude of endplate potentials. 3. The quantal content of endplate potentials was increased by BDM in a reversible, concentration-dependent manner. 4. The frequency of miniature endplate potentials was not changed by 10 mM BDM in the presence of normal or raised potassium concentrations, indicating that BDM does not change quantal content by a direct effect on calcium channels or on steady-state intracellular calcium concentration. 5. A change in the time course of the extracellularly recorded nerve terminal action potential caused by BDM was similar to the change produced by 4-aminopyridine (4-AP). 6. The increase in quantal content produced by BDM was only slightly reduced in the presence of 1 mM tetraethylammonium (TEA) but was significantly reduced in the presence of 0.5 to 1 mM 4-AP. 7. It was concluded that BDM blocks a 4-AP-sensitive potassium conductance in motor nerve terminals and, by increasing the duration of the action potential in this way, increases evoked transmitter release.     

Quantitative effects of cerebral infarction on spatial learning in rats.

Outcome following stroke is difficult to measure because the behavioral response to infarction is variable. We hypothesized that cognitive function, such as spatial learning, may be a reproducible and sensitive outcome variable. We developed an animal model of multifocal cerebral ischemia in order to study the effects of infarction on learning. To cause ischemia, several hundred microspheres were injected into the internal carotid arteries of rats. After ischemia, behavior was measured using a global rating and a Morris water maze. Postmortem serial brain sections were stained and the size of the infarctions was measured. We found that intracerebral microspheres caused cortical infarction and an impairment of spatial learning. This impairment was not due to occlusion of the internal carotid artery and was not found in animals who received a sham injection of saline. The degree of learning impairment was not correlated with the volume density of the infarctions or with the volume density of the remaining cerebral hemisphere. The learning impairment clearly differentiated normal from lesioned animals, and the impairment was probably due to a delay in acquisition of spatial information rather than a defect in retention or retrieval. Measurement of learning deficit after cerebral ischemia is an efficient and sensitive method for evaluating new stroke treatments and possibly for exploring structure function relationships.     

Highly resolving two-dimensional gels for protein sequencing.

Two-dimensional (2D) PAGE, using carrier ampholytes for the first-dimension separation, has provided a tool for the simultaneous analysis of cellular proteins. To extend the utility of 2D PAGE to the preparative level, we have investigated the use of immobilized pH gradients (IPG) for the first-dimension separation. The results we have obtained indicate that as much as 1 mg of cellular protein can be loaded onto a single IPG gel without loss of resolution. Mutant polypeptides previously detected in carrier ampholyte-based 2D gels were equally detectable in IPG-based 2D gels. With IPG gels several hundred cellular polypeptides can be isolated, from as few as 10 gels, in sufficient amount for sequencing with current sequencing technology. We therefore conclude that IPG greatly enhances the prospects for the large-scale sequencing of cellular proteins for the development of 2D gel-related protein data bases and for the identification of new polypeptide gene products, with the attendant implications for a genome sequencing effort.     

Familial and socioeconomic influences on children''s well-being: An examination of preschool children in Kenya

As patterns of family formation change, it is important to know how children's lives are affected by their parents' marital and socioeconomic circumstances. Using data from the 1993 Kenya Demographic and Health Survey, this study shows that children of never married and formerly married mothers have significantly higher probabilities of polio dropout and acute undernutrition than those of monogamously married mothers. The number of male household members of working age greatly enhances the chances of full immunization and the nutritional status of children whose mothers were previously married. For children of never married mothers, the benefits of residing with males of working age are largely a function of ethnicity. The results also show that, although children are not disadvantaged nutritionally when their fathers have more than one wife, polygyny is associated with a higher probability of polio dropout and lower probability of full immunization than monogamy. Higher socioeconomic status is associated with a greater probability of full immunization and a lower probability of malnutrition but socioeconomic factors do not explain the effects of mothers' marital status. The findings underscore the complex realities of family interaction and the importance of the broader social context in accounting for variations in child welfare across diverse marital situations.