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Biomedical subjects

A H Mohammed

Publications and source records attributed to A H Mohammed.

At least 37 records · Page 2Linked to original sources

Glucocorticoid receptor and NGFI-A gene expression are induced in the hippocampus after environmental enrichment in adult rats.

Environmental manipulation alters hippocampal glucocorticoid receptor (GR) expression in neonatal rats, but effects in adults have not been documented. Chronic environmental enrichment (EE) increases nerve-growth factor (NGF) concentrations in the adult rat hippocampus. Here we demonstrate that EE induces GR, but not mineralocorticoid receptor (MR) gene expression in specific hippocampal subfields (CA1 and CA2). This is accompanied by increased expression of mRNA encoding the (NGF-induced) immediate early gene NGFI-A in CA2, whereas expression of NGFI-B mRNA decreased in CA1 and CA2. The nature of any relationship between NGF, the transcription factors and GR remains to be determined, but the results demonstrate that chronic environmental manipulations alter hippocampal GR gene expression in adult rats.

Animals↗

[Early stimulation--good memory in old age?].

For better or worse, the importance of neonatal stimulation has attracted increasing attention in recent years. Results from animal studies provide a hint of possible beneficial consequences for humans, even in a geriatric context.

Aged↗

Environmental influences on the central nervous system and their implications for the aging rat.

Two methods of providing environmental stimulation that were introduced in the 1950s have guided much research on neurobehavioural plasticity. These are neonatal handling and environmental enrichment. Neonatal handling has been shown to permanently affect behaviour and endocrine responses. Recently this manipulation has been shown to have important influences on the aging individual, protecting the hippocampus from age-related dysfunction and neuronal loss. These effects are mediated, in part, by keeping glucocorticoid levels low. This has been characterised by, among other things, elevated expression of glucocorticoid receptors in the hippocampus. Earlier studies have failed to present convincing evidence for differences in hormonal variables between animals housed in enriched and impoverished environments, and have not consistently reported changes in the hippocampus. Recent data from our laboratories have shown that adult animals housed in enriched environments had, like neonatally-handled rats, higher expression of the gene encoding glucocorticoid receptors in the hippocampus. Taken together with the induction of NGF and NGFIA gene expression in the hippocampus of enriched animals, these results implicate genes encoding transcription factors and glucocorticoid receptors in the cascade of events leading to environmentally induced cerebral changes. In addition, these results suggest that environmental enrichment in adulthood, like neonatal handling, may have the potential to protect the aging hippocampus from glucocorticoid neurotoxicity.

Aging↗

Alzheimer's disease: molecular genetics and transgenic animal models.

Disease-causing mutations in the amyloid precursor protein (APP) gene have been found on chromosome 21 during the last 2 years in some early onset Alzheimer's disease (AD) families. Genetic evidence shows that other genes than the APP are also involved in the aetiology of AD. Linkage to a loci on chromosome 14 has been found in early onset disease. The identification of APP mutation has led to the realization that APP mismetabolism is a central event in the aetiology and pathogenesis of the disease. Experiments to test this in transgenic mice have so far met with little success. There are many possible explanations for the problems to generate transgenic mice. These include the possibilities that mice are incapable of developing AD for reasons dependent on their APP sequence; and that appropriate regulation of APP gene is required for pathology to develop. Current attempts that seem promising to model the disease pathology are the use of homologous recombination to insert the pathogenic mutation and transfection of YACs into transgenic animals.

Aged↗

Subchronic MK-801 treatment to juvenile rats attenuates environmental effects on adult spatial learning.

Treatment with the non-competitive NMDA receptor blocker MK-801 (0.16 mg/kg), given to juvenile rats before and after the exposure to an enriched environment on alternate days for 4 weeks, attenuated the improvements in spatial learning and open field adaptation which resulted from such environmental stimulation. Drug treatment affected the consolidation of experiences as an injection given after exposure to the enriched environment was needed to demonstrate this effect. In addition, MK-801 administration diminished the adverse effect of stimulus deprivation-the slow learning rate normally seen in rats housed in impoverished environment. Radioligand binding studies showed that drug treatment decreased [3H]MK-801 binding sites in cortex. The learning, activity and receptor binding effects were measured 4 months from cessation of the drug treatment and environmental manipulation. The results support the role of NMDA receptors in mediating cognitive changes associated with environmental stimulation.

Animals↗

Effects of cholinesterase inhibitors on learning and memory in rats: a brief review with special reference to THA.

Research on memory enhancing effects of acetylcholinesterase (AChE) inhibitors was stimulated by the finding of diminished cholinergic markers in patients with Alzheimer's disease, and the correlation of cognitive impairment to cholinergic deficits in these patients. The rationale for the use of AChE inhibitors is based on their abilities to prevent breakdown of acetylcholine released from surviving nerve terminals. In experimental animals the AChE inhibitor has been found by some investigators to be efficacious in improving cognitive function. Recent work has focused more on the performance and memory enhancing effects of tetrahydroaminoacridine (THA). THA has been found to improve performance in experimental animals with cognitive impairments induced by a variety of experimental manipulations such as by pharmacological blockade, cholinergic lesions, chronic alcohol or barbital treatment and ischemic lesion. These findings are compatible with the view that AChE inhibitors can be efficacious in "restoration" of some cholinergic functions.

Alzheimer Disease↗

Hippocampal nerve growth factor levels are related to spatial learning ability in aged rats.

Brain nerve growth factor (NGF) was determined in two groups of aged rats: 'good' and 'poor' performers. The animals were selected out of a population of 40 aged rats (26-28 months old) trained in a spatial learning task. Animals performing well in the test had significantly higher NGF in the hippocampus when compared to 'poor' performers. No differences in the levels of NGF were found in the cortex, septum and cerebellum. The results implicate hippocampal NGF in cognitive functioning of aged rats, and suggests that the forebrain cholinergic neuronal atrophy which has been observed in cognitively impaired aged rats may be due to reduced availability of target-derived NGF.

Aging↗

Leukotrienes in orthodontic tooth movement.

Prostaglandins (PGs) and leukotrienes (LTs) are products of arachidonic acid conversion. PGs have an established role in mediating orthodontic tooth movement. The role of LTs in modulating or mediating orthodontic tooth movement was investigated in this study. One hundred thirty-two Sprague-Dawley rats were used; the animals weighed 300 to 400 gm with equal numbers of male and female rats. They were divided into five main groups of 24 animals each and a sham group of 12 animals. An orthodontic appliance was placed and activated on all the animals except the sham group; in this group the appliances were not active. Each main group was given one of the following treatments daily: distilled water, 5% gum arabic solution, PG synthesis inhibitor indomethacin, LT synthesis inhibitor AA861, and a combination of both drugs. Each group was divided into six subgroups of four animals; the animals were killed at either 1, 3, 5, 7, 10, or 14 days, and tooth movement measured. The three sham subgroups received distilled water and were killed at 1, 7, or 10 days. The first maxillary molar (the moved tooth) and surrounding tissues were removed from all animals in the sham group and the subgroups killed at 1, 7, and 10 days in the gum arabic solution group and the LT synthesis inhibitor group. Prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) were extracted, measured with radioimmunoassay (RIA), and standardized per milligram of protein in the sample. A significant inhibition of tooth movement occurred beginning on day 7 in the indomethacin, AA861, and combination groups; there was no significant difference among these groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Development and evaluation of an enzyme-linked immunosorbent assay for endotoxin in milk.

A double antibody sandwich enzyme-linked immunosorbent assay (ELISA) was developed for the detection of endotoxin in milk samples. Bovine and rabbit antisera raised in response to vaccination with the J5 mutant of Escherichia coli 0111:B4 were used. Antiserum to this mutant has been shown to be cross-reactive with endotoxin from other gram-negative organisms. Known quantities of endotoxin were added to milk samples to generate a standard curve. Acid treatment of whole milk enhanced the detection of endotoxin as compared to untreated whole milk, skim milk and chloroform-treated milk. Milk samples from experimentally induced mastitic cows were then assayed for endotoxin content. Recovery of endotoxin, as measured by ELISA, positively correlated with the amount of endotoxin infused and the time post-infusion of sampling. However, when endotoxin from these samples was quantitated using the Limulus Amebocyte Lysate (LAL) assay, readings tended to increase, suggesting false-positive reactions with the LAL assay. Milk samples from cases of clinical mastitis were assayed by ELISA with 64% of these showing measurable levels of endotoxin. While further studies of this assay are needed, refinements may produce an assay important for clinical applications.

Animals↗

Haemoproteus columbae: course of infection, relapse and immunity to reinfection in the pigeon.

Studies were performed on the course of infection, relapse, and immunity to reinfection in 11 young pigeons infected with the avian malaria parasite Haemoproteus columbae Kruse. The prepatent period in our experiments varied between 22 and 37 days. The intensity and length of the initial infection period showed wide variations. During this period an initial periodicity of gametocyte production of about 12 days with peaks at about 6-8 and 18-20 days after patency was observed. The various modes of infection (fly bite, intramuscular, intravenous, or intraperitoneal inoculation of sporozoites) did not influence the intensity of the initial infection. No pathogenicity due to heavy infection with the parasite was observed. There was no periodicity of relapse occurrence, nor any correlation between the frequency of relapse and the intensity of the initial infection, and the phenomenon was not influenced by seasonal changes. Pigeons (Columba livia) that had recovered from previous infections were susceptible to reinfection, whereas pigeons with chronic infection acquired immunity (premunition).

Animals↗

Studies of growth and development of gametocytes in Haemoproteus columbae Kruse.

As determined by their ability to exflagellate and round up, it took the macrogametocyte and the microgametocyte of Haemoproteus columbae in pigeons 68 and 116 h, respectively, after patency to reach maturity. Pigment granules appeared in the undifferentiated gametocytes 8 h after invasion of blood. Vacuoles were observed in young gametocytes and persisted in the older forms. The growth curve of H. columbae is close to the sigmoidal curve for growth in protozoa. Multiple infection was noticed in pigeons with high levels of parasitemia, but no more than 2 gametocytes reached maturity; such multiple infections were rare in relapses. The sex ratio of the gametocytes was 1:1. Strong lateral displacement of the nuclei of infected erythrocytes was the rule; hypertrophy was negligible.

Animals↗

Schizogony in Haemoproteus columbae Kruse.

To fill in some of the gaps in our knowledge of Schizogony of Haemoproteus columbae Kruse, transmission experiments involving inoculation into pigeons (Columba livia Gmelin) of sporozonites from salivary glands of the hippoboscid fly Pseudolynchia canariensis (Macquart) were carried out. We were unable to detect prepatent schizonts or to observe schizogonic development when infection became chronic. Schizonts were mainly confined to lung tissue. Observations of parapatent schizonts were made in smears and tissue sections. A variety of forms was found. Cytomeres were rarely encountered. Two types of morphologically distinct merozoites were seen. One type was twice as large as large as the other and was thought to repeat the process of schizogony several times before invading erythrocytes. Schizonts with cytoplasmic clefts were not common in our material due to the fixatives used (Bouin's and Carnoy's). Merozoites were occasionally observed inside monocytes, probably being phagocytosed.

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