Search

In the normal ageing cortex of the brain there is a group of dying neurons with shrinking dendritic trees and a group of surviving neurons with expanding dendritic trees. The ageing process affects neurotransmitter systems, including glutamate neurons and NMDA receptors. Calcium is an important signaling molecule. It enters brain cells through NMDA receptors and voltage-gated calcium channels. Since NMDA receptors play an important role in brain plasticity, calcium uptake through NMDA receptors can be used as a measure of brain activity. This study therefore sought to determine the effect of ageing on NMDA-stimulated Ca(2+) uptake into barrel cortex slices of Spontaneously Hypertensive Rats (SHR) compared to control Wistar-Kyoto rats (WKY). Young rats (prepuberty, 4-6 weeks) and adult rats (14-16 weeks) were used in the study. The results show a significant decrease in NMDA-stimulated Ca(2+) uptake in adult rats compared to their young litter-mates. It can be concluded that ageing negatively affects NMDA-stimulated Ca(2+) uptake into barrel cortex slices of SHR and WKY.

Exposure to an enriched environment provides animals with informal learning opportunities and is associated with increases in brain size, cortical thickness, neuron size, dendritic branching, spine density, and number of synapses per neuron. The NMDA receptor is involved in synaptic plasticity. This study sought to determine the effect of exposure to an enriched environment on NMDA receptor function in barrel cortex slices of spontaneously hypertensive rats (SHR) and their control Wistar-Kyoto (WKY) rats. An assortment of items such as PVC pipes, metal pipes, metal boxes, metal ladders, and a polystyrene maze, were placed successively in the cages of test animals to create an enriched environment. After 2 weeks, the rats were killed. Their brains were rapidly removed, cooled in continuously oxygenated HEPES buffer (pH 7.4), and sliced in a vibratome to produce 0.35-mm thick slices. The barrel cortex was dissected from slices corresponding to 8.6-4.8 mm anterior to the interaural line and incubated with 45Ca2+ and 100 microM NMDA for 2 min. There was no difference between rats exposed to an enriched environment and rats kept in standard cages. Enrichment of environment did not alter NMDA-stimulated Ca2+ uptake into barrel cortex of SHR and WKY.

The spontaneously hypertensive rat (SHR) is an accepted model for attention-deficit hyperactivity disorder (ADHD) since it displays the major symptoms of ADHD (hyperactivity, impulsivity, and poor performance in tasks that require sustained attention). We have previously shown that glutamate activation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors released significantly more norepinephrine from SHR prefrontal cortex slices than control Wistar-Kyoto (WKY) rats. The aim of this study was to determine whether N-methyl-D-aspartate (NMDA) receptor function is disturbed in the prefrontal cortex of SHR. Prefrontal cortex slices were incubated with 45Ca2+ in the presence or absence of 100 microM NMDA for 2 min. Activation of NMDA receptors stimulated significantly less Ca2+ uptake into prefrontal cortex slices of SHR than control WKY (2.8 +/- 0.17 vs. 3.7 +/- 0.38 nmol/mg protein, respectively, P < 0.05). Basal Ca2+ uptake into SHR slices was not significantly different from WKY. These findings are consistent with suggestions that the intracellular concentration of calcium is elevated and therefore the concentration gradient that drives calcium into the cell is decreased in SHR compared to WKY. Impaired NMDA receptor function in the prefrontal cortex of SHR could give rise to impaired cognition and an inability to sustain attention.

The spontaneously hypertensive rat (SHR) is used as a model for attention-deficit hyperactivity disorder (ADHD), since it has behavioural characteristics that resemble the behavioral disturbances of ADHD, namely hyperactivity, failure to sustain attention, and impulsiveness. The aim of this study was to establish whether N-methyl-D-aspartate (NMDA) receptor function was altered in barrel cortex slices of 4- to 6- week-old SHR compared to their normotensive Wistar-Kyoto (WKY) control rats. The barrel cortex was dissected from brain slices corresponding to antero-posterior coordinates 8.7-4.8 mm with reference to the Paxinos and Watson (1986) atlas and divided into rostral, middle, and caudal regions. 45Ca2+ uptake was stimulated by incubating test slices in buffer containing 100 microM NMDA for 2 min at 35 degrees C. Total 45Ca2+ uptake into the entire barrel cortex as well as uptake into all regions of SHR barrel cortex was lower compared to WKY. Basal uptake into the entire barrel cortex as well as uptake into rostral and caudal regions of SHR barrel cortex was lower than WKY but basal uptake into the middle region was the same for both strains. There was no difference between SHR and WKY in NMDA-stimulated 45Ca2+ uptake into barrel cortex slices except for significantly lower NMDA-stimulated uptake into the middle region of SHR barrel cortex compared to WKY. These findings suggest that calcium metabolism is disturbed in the somatosensory cortex of SHR but that NMDA receptor function is not altered.

The rat is a nocturnal animal and uses its vibrissae extensively to navigate its environment. The vibrissae are linked to a highly organized part of the sensory cortex, called the barrel cortex which contains spiny neurons that receive whisker specific thalamic input and distribute their output mainly within the cortical column. The aim of the present study was to develop a method to evaluate glutamate receptor function in the rat barrel cortex. Long Evans rats (90-160 g) were killed by cervical dislocation and decapitated. The brain was rapidly removed, cooled in a continuously oxygenated, ice-cold Hepes buffer (pH 7.4) and sliced using a vibratome to produce 0.35 mm slices. The barrel cortex was dissected from slices corresponding to 8.6 to 4.8 mm anterior to the interaural line and divided into rostral, middle and caudal regions. Depolarization-induced uptake of 45Ca2+ was achieved by incubating test slices in a high K+ (62.5 mM) buffer for 2 minutes at 35 degrees C. Potassium-stimulated uptake of 45Ca2+ into the rostral region was significantly lower than into middle and caudal regions of the barrel cortex. Glutamate had no effect. NMDA significantly increased uptake of 45Ca2+ into all regions of the barrel cortex. The technique is useful in determining NMDA receptor function and will be applied to study differences between spontaneously hypertensive rats (SHR) that are used as a model for attention deficit disorder and their normotensive control rats.