Calcium Channel Density and Hippocampal Cell Death with Age in Long-Term Culture

Abstract

The expression of voltage-gated calcium (Ca 2ϩ ) channel activity in brain cells is known to be important for several aspects of neuronal development. In addition, excessive Ca 2ϩ influx has been linked clearly to neurotoxicity both in vivo and in vitro; however, the temporal relationship between the development of Ca 2ϩ channel activity and neuronal survival is not understood. Over a period spanning 28 d in vitro, progressive increases in high voltage-activated whole-cell Ca 2ϩ current and L-type Ca 2ϩ channel activity were observed in cultured hippocampal neurons. On the basis of single-channel analyses, these increases seem to arise in part from a greater density of functionally available L-type Ca 2ϩ channels. An increase in mRNA for the ␣ 1 subunit of L-type Ca 2ϩ channels occurred over a similar time course, which suggests that a change in gene expression may underlie the increased channel density. Parallel studies showed that hippocampal neuronal survival over 28 d was inversely related to increasing Ca 2ϩ current density. Chronic treatment of hippocampal neurons with the L-type Ca 2ϩ channel antagonist nimodipine significantly enhanced survival. Together, these results suggest that age-dependent increases in the density of Ca 2ϩ channels might contribute significantly to declining viability of hippocampal neurons. The results also are analogous to patterns seen in neurons of aged animals and therefore raise the possibility that long-term primary neuronal culture could serve as a model for some aspects of aging changes in hippocampal Ca 2ϩ channel function.

Effects of P2Y1 receptor on glial fibrillary acidic protein and glial cell line-derived neurotrophic factor production of astrocytes under ischemic condition and the related signaling pathways

“…All procedures were conducted in accordance with NIH guidelines for the care and use of laboratory animals. Heterogeneous primary cells were cultured from embryonic day 16 (E16) SD rat embryos [9] . Pregnant SD rat was anesthetized with 10% chloral hydrate (0.4 g/kg, i.p.).…”

Stress and the Aging Hippocampus

“…The activity of L-type calcium channels increases in hippocampal CA1 pyramidal neurons of aging rats and results in an increased afterhyperpolarization (70). In cultured embryonic hippocampal neurons that are maintained for 28 days, there is an increase in calcium channel activity and in after-hyperpolarization that is accompanied by decreased neuronal survival; blocking L-type calcium channels increased neuronal survival (116). It is interesting to note that the increased after-hyperpolarization is associated with an enhanced induction of long-term depression in CA1 pyramidal neurons and an impaired induction of long-term potentiation (105).…”

“…Some initial results indicate that diabetes may accelerate stress-induced dendritic atrophy in the hippocampus and promote stress-induced neuronal damage (84,121). A third approach is to use hippocampal cell culture models and study the interaction of androgens, estrogens, glucocorticoids, and excitatory amino acids in producing excitotoxic damage (48,116,117,126). As noted above, the vulnerability to excitotoxicity in hippocampal neurons has been related to increased calcium channel activity that develops with increasing age in culture (116).…”

“…A third approach is to use hippocampal cell culture models and study the interaction of androgens, estrogens, glucocorticoids, and excitatory amino acids in producing excitotoxic damage (48,116,117,126). As noted above, the vulnerability to excitotoxicity in hippocampal neurons has been related to increased calcium channel activity that develops with increasing age in culture (116). The cell culture approach has been extended recently to demonstrate the protective effects of another steroid that declines with age in humans, namely, dehydroepiandrosterone (DHEA), toward NMDA-induced neurotoxicity (65).…”

Effect of Vitamin E on Blood-Brain Barrier Permeability in Aged Rats with PTZ-Induced Convulsions

“…Considerable modifications of synaptic connections, electrotonic coupling, features of receptors and channels, numbers and functions of specific-type neurons within neuronal networks develop due to aging [32][33][34][35][36][37]. Besides this, it was reported that age-dependent alterations also develop in the sodium/potassium equilibrium and extracellular volume, and these alterations noticeably affect neuronal synchronization and excitability [38][39][40][41]. Thus, much higher doses of vitamin E are needed to provide its protective effect against the increased permeability of the BBB during epileptic attacks in old organism.…”