Cerebral cortex, cell death

Different cell populations die at different times. For example, in rodents, sympathetic neurons are pruned down by mid-gestation, whereas for cranial regions of the neuraxis the phase of cell death extends into the perinatal period. In the mammalian cerebral cortex, it has been estimated that approximately 40% to 50% of neurons die, and this process is completed in rat by the third postnatal week in concomitance to synapto-genesis (Ferrer et ah, 1990 Fig. 1.7). 

Ferrer, L, Bernet, E., Soriano, E., del Rio T., and Fonseca, M. (1990) Naturally occurring cell death in the cerebral cortex of the rat and removal of dead cells by transitory phagocytes. Neuroscience 39 451 58. 

Thus, this excess excitation leads to cell death by either apoptosis or necrosis in the neurons affected, which was found to be mostly in the hippocampus and amygdale, although some occurred in the cerebral cortex also. 

Blaschke AJ, Staley K, Chun J. 1996. Widespread programmed cell death in proliferative and postmitotic regions of the fetal cerebral cortex. Development 122 1165-1174. 

In spite of the increased activities of SOD-1 and GPx and normal catalase activity, increased lipid peroxides in the blood plasma of DS patients have been reported (K10), as has as an increased accumulation rate of age pigments (i.e., lipofuscin and ceroid, known products of lipid peroxidation) (K9). In addition, an early study showed increased lipid peroxides in the cerebral cortex of DS fetal brains (B15). More recently, cortical neurons from fetal DS and age-matched normal brains were shown to differentiate normally early in cell cultures. However, DS neurons subsequently degenerated and underwent apoptosis, whereas the normal cells remained viable (B18). In addition, the DS neurons exhibited a three- to fourfold increase in reactive oxygen species and increased lipid peroxidation that preceded cell death. Importantly, DS neuron degeneration could be prevented by treatment with the free radical spin trap A-ferf-butyl-2-sulphophenylnitrone, the... 

Fig. 3.12. A Protective effect of (-)-BPAP in the high micromolar concentration range, with a peak effect at 10 6M concentration, against serum-free condition induced cell death in low-cell-density culture of the cerebral cortex from E17 rats. B Lack of a protective effect of (-)-BPAP under the same conditions in the low nanomolar concentration range. Experiments were carried out in triplicate. Data are the mean SEM from six independent experiments. The data were analyzed using Student s f-test after multiple comparisons of ANOVA. P value was < 0.05 compared with the results in the vehicle-treated culture. See Hamabe et al. (2000) for methodology...

The first study of the enhancer effect on cultured cortical neurons was performed with (-)-BPAP on a primary culture of rat cerebral cortex. In this experiment the rapid cell death of the cortical neurons was measured in serum-free culture. It was shown that in a low-cell-density culture cortical neurons rapidly die. (-)-BPAP, as first shown by Hamabe et al., significantly protected the cortical neurons against serum-free-condition-induced cell death in the high concentration range (see Fig. 2 in Hamabe et al. 2000). The protective effect of (-)-BPAP, with a peak effect at 10-6 M concentration, is shown in Fig. 3.12A. However, in striking contrast to the finding on cultured rat hippocampal neurons (see Knoll et al. 1999, Fig. 5), (-)-BPAP did not exert an enhancer effect on the cultured rat cortical neurons in the nanomolar concentration range. This is shown in Fig. 3.12B. 

Alzheimer s disease is primarily the result of degeneration or death of nerve cells in the cerebral cortex and in areas that usually control functions such as memory, personality, logical thinking, and other. As the nerve cells become withered and small, they cause the enlargement of the ventricles of the brain. Recent events are not remembered, the individual is not able to perform calculations or make plans and decisions. Abrupt personality changes alarm family members and friends thus disabling the person from functioning normally. 

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