Activity-dependent survival and enhanced turnover of calcium in cultured rat cerebellar granule neurons

Kohara, Keigo; Ono, Tsutomu; Tominaga-Yoshino, Keiko; Shimonaga, Tomokazu; Kawashima, Seiichi; Ogura, Akihiko

doi:10.1016/s0006-8993(98)00894-4

Cited by 11 publications

(6 citation statements)

References 19 publications

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“…Cultures were prepared from source animals by standardized procedures described previously (Kohara et al . 1998).…”

Section: Methodsmentioning

confidence: 99%

“…Cultures were prepared from source animals by standardized procedures described previously (Kohara et al, 1998). Brie¯y, rodent neonates were killed under ether anaesthesia at 8 days of age.…”

Section: Cellsmentioning

confidence: 99%

“…In the developing brain, neurons are produced in excess and selected by a process called activity-dependent survival, whereby only neurons that have succeeded in establishing synaptic connections and are functioning properly can survive (see Oppenheim, 1991 for review). The cerebellar granule neurons (CGNs) isolated from rat neonates and transferred to cell culture are often used as a model system for the analysis of this activity-dependent survival (Gallo et al, 1987;Segal et al, 1992;Kohara et al, 1998). They do not form active synaptic connections per se and survive only if synaptic activity is mimicked by an exogenously applied depolarizing agent (KCl or glutamate).…”

Section: Introductionmentioning

confidence: 99%

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Depolarization‐dependent survival of cultured mouse cerebellar granule neurons is strain‐restrained

Fujikawa

Tominaga-Yoshino

Okabe

et al. 2000

Eur J of Neuroscience

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Cerebellar granule neurons (CGNs) isolated from the rat are often used as a model system for the analysis of activity-dependent survival of neurons. These cells do not survive in culture without addition of a depolarizing agent (KCl or glutamate) to the medium. However, it has been reported that mouse CGN behave differently. Here we found that the requirement for depolarization for the survival of the mouse CGN was strain-dependent, which may be important for future analyses using transgenic animals. CGNs from the Balb/C mouse could survive without KCl addition, whereas CGNs from the C57Bl/6 mouse could not (similar to the rat CGN). The survival-promoting activity of the Balb/C mouse CGNs was transferable by coculturing. However, the medium of the Balb/C mouse CGN culture was ineffective, suggesting that the neurotrophic substance that is supposed to be released is labile. Although we are yet to specify the substance, it might be independent of neurotrophins. It is necessary to select the strain of mouse in the production of transgenic animals for the analyses of activity-dependent neuronal survival.

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“…Cultures were prepared from source animals by standardized procedures described previously (Kohara et al . 1998).…”

Section: Methodsmentioning

confidence: 99%

Section: Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Depolarization‐dependent survival of cultured mouse cerebellar granule neurons is strain‐restrained

Fujikawa

Tominaga-Yoshino

Okabe

et al. 2000

Eur J of Neuroscience

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“…It was concluded that the polyglutamine expansion prevents the ␣1A from performing its protective functions as ␣1 activity is required for survival. 96,97 This intriguing loss-of-function model has yet to be replicated.…”

Section: Polyglutamine-mediated Toxicitymentioning

confidence: 99%

Molecular Pathogenesis of Spinocerebellar Ataxia Type 6

Kordasiewicz

Gómez

2007

Neurotherapeutics

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Summary: Spinocerebellar ataxia type 6 (SCA6) is a neurodegenerative disorder caused by abnormal expansions of a trinucleotide CAG repeat in exon 47 of the CACNA1A gene, which encodes the ␣1A subunit of the P/Q-type voltage-gated calcium channel. The CAG repeat expansion is translated into an elongated polyglutamine tract in the carboxyl terminus of the ␣1A subunit. The ␣1A subunit is the main pore-forming subunit of the P/Q-type calcium channel. Patients with SCA6 suffer from a severe form of progressive ataxia and cerebellar dysfunction. Design of treatments for this disorder will depend on better definition of the mechanism of disease. As a disease arising from a mutation in an ion channel gene, SCA6 may behave as an ion channelopathy, and may respond to attempts to modulate or correct ion channel function. Alternatively, as a disease in which the mutant protein contains an expanded polyglutamine tract, SCA6 may respond to the targets of drug therapies developed for Huntington's disease and other polyglutamine disorders. In this review we will compare SCA6 to other polyglutamine diseases and channelopathies, and we will highlight recent advances in our understanding of ␣1A subunits and SCA6 pathology. We also propose a mechanism for how two seemingly divergent hypotheses can be combined into a cohesive model for disease progression.

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“…Numerous studies highlight the important role of depolarization and calcium entry for neuronal survival (15,16,21,39). Furthermore, the team of Ogura demonstrated the key role of calcium turnover in depolarized granule cells survival (40,41). Calciumdependent survival can also act dominantly over serum Figure 7.…”

Section: Role Of Voltage-dependent Calcium Entry In Prevention Of Neumentioning

confidence: 99%

Calcium/calmodulin‐dependent protein kinase type IV (CaMKIV) inhibits apoptosis induced by potassium deprivation in cerebellar granule neurons

et al. 2001

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The neuroprotective mechanisms of the Ca2+/calmodulin kinase (CaMK) signaling pathway were studied in primary cerebellar neurons in vitro. When switched from depolarizing culture conditions HK (extracellular K+ 30 mM) to LK (K+ 5 mM), these neurons rapidly undergo nuclear fragmentation, a typical feature of apoptosis. We present evidence that blockade of L-type Ca2+ channels (nifedipine sensitive) but not N/P/Q-type Ca2+ channels (omega-conotoxin MVIIC sensitive) triggered apoptosis and CPP32/caspase-3-like activity. The entry into apoptosis was associated with a progressive caspase-3-dependent cleavage of CaMKIV, but not of CaMKII. CaMKIV function in neuronal apoptosis was further investigated by overexpression of CaMKIV mutants by gene transfer. A dominant-active CaMKIV mutant inhibited LK-induced apoptosis whereas a dominant-negative form induced apoptosis in HK, suggesting that CaMKIV exerts neuroprotective effects. The transcription factor CREB is a well-described nuclear target of CaMKIV in neurons. When switched to LK, the level of phosphorylation of CREB, after an initial drop, further declined progressively with kinetics comparable to those of CaMKIV degradation. This decrease was abolished by caspase-3 inhibitor. These data are compatible with a model where Ca2+ influx via L-type Ca2+ channels prevents caspase-dependent cleavage of CaMKIV and promotes neuronal survival by maintaining a constitutive level of CaMKIV/CREB-dependent gene expression.

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Activity-dependent survival and enhanced turnover of calcium in cultured rat cerebellar granule neurons

Cited by 11 publications

References 19 publications

Depolarization‐dependent survival of cultured mouse cerebellar granule neurons is strain‐restrained

Depolarization‐dependent survival of cultured mouse cerebellar granule neurons is strain‐restrained

Molecular Pathogenesis of Spinocerebellar Ataxia Type 6

Calcium/calmodulin‐dependent protein kinase type IV (CaMKIV) inhibits apoptosis induced by potassium deprivation in cerebellar granule neurons

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