Biomedical subjects

A Jennifer Morton

Publications and source records attributed to A Jennifer Morton.

21 records · Page 2Linked to original sources

PubMed2003

RAGE is expressed in pyramidal cells of the hippocampus following moderate hypoxic-ischemic brain injury in rats.

The receptor for advanced glycation end products (RAGE) is a multi-ligand member of the immunoglobulin superfamily of cell surface molecules. The RAGE-ligand interaction has a putative role in a range of chronic disorders and is also known to contribute to both inflammatory/degenerative processes as well as regeneration in peripheral nerve injury. We have investigated the expression of RAGE in the moderate hypoxic-ischemic (HI) rat brain injury model in order to determine if this receptor is involved in the cellular perturbation mediated by ischemic stress. RAGE mRNA levels were detected by in situ hybridization using a DIG-labelled 48 mer oligonucleotide probe. Results showed a high level of expression of RAGE mRNA in the CA1/2 pyramidal cell layer of the hippocampus on the lesioned side of the brain 72 h after a moderate hypoxic-ischemic insult. RAGE was not expressed on the control side of the hippocampus. The RAGE-positive cells had a unique morphology, being angular in shape and atrophied with a condensed cell nucleus. They were NeuN-positive and were identified as dying cells by staining with thionin/acid fuchsin. A subset of cells was positive for cleaved Caspase-3, a marker for apoptosis. Together these data show that RAGE is expressed in dying neurons and suggest that RAGE may have a role in neuronal cell death mediated by ischemic stress. Identification of the ligand for RAGE in the ischemic brain may lead to a better understanding of RAGE-mediated cellular dysfunction in the CNS.

Animals↗

PubMed2003

Microglia density decreases with age in a mouse model of Huntington's disease.

Huntington's disease (HD) is characterized by selective neuronal loss and reactive gliosis. In the R6/2 transgenic HD mouse model, there is no selective cell loss, although astrocytosis has been reported. Since there have been no previous studies on microglia in this model, we have undertaken a detailed investigation of microglia in six different forebrain regions in the R6/2 mouse and their wild-type littermates at two time points. Microglia were identified using the histochemical marker isolectin B4 and interactions of genotype, region, and age were analyzed. Results showed that there was a significant decrease in the number of microglia with age in both wild-type and R6/2 brains, which was more pronounced in the transgenic mouse. There were also morphological changes with age observed in both genotypes. As early as 7 weeks of age, structural microglial abnormalities could be seen in R6/2 brains, including bulbous swellings and long stringy processes; comparable changes were seen at 16 weeks in wild-type brains. At 14.5 weeks, microglia in R6/2 mouse brains were smaller in size with condensed nuclei and fragmentation of their processes. We suggest that the density and morphology of microglia change with normal aging and that this process is accelerated in R6/2 brains. Such changes in the dynamic status of microglia may lead to an impairment of their neurosupportive functions. Further studies are needed to understand better the role of microglia in aging and neurodegeneration.

Aging↗

PubMed2002

The role of dopamine in motor symptoms in the R6/2 transgenic mouse model of Huntington's disease.

In both Huntington's disease (HD) patients and genetic mouse models of HD, there is a pre-symptomatic loss of dopamine (DA) receptors, suggesting that dysfunctional dopaminergic neurotransmission may be involved in early HD presentation. However, the role of DA in HD symptoms is not fully understood. In this study, we examined the possibility that dysfunctional dopaminergic neurotransmission contributes to the progressive decline in motor function of a transgenic mouse model of HD (R6/2 line). We found that R6/2 mice display an age-dependent abnormal behavioural response to (+)-methamphetamine (METH) and a dose-dependent increase in sensitivity to METH toxicity compared with wild-type (WT) mice. R6/2 mice also showed an attenuated response to cocaine, indicating that DA release may be compromised. Striatal DA levels were reduced in R6/2 mice by 9 weeks of age. Replacement of DA by chronic treatment with laevodopa (L-DOPA, administered as Sinemet) caused short-term improvements in activity and rearing behaviour, and abolished abnormal spontaneous hindlimb grooming. However, long-term treatment with L-DOPA had deleterious effects on survival and rotarod performance of R6/2 mice. These results suggest that dysfunctional DA neurotransmission contributes to phenotype development in R6/2 mice and thus also may be important in symptom progression in HD.

Aging↗