First, we simulated neuronal turnover by assuming that neurons "die" and are "born" randomly through a Poisson process during network formation.
Interestingly, not only do a smaller number of mature neurons die after nerve transection, but the rate of neuronal death is also much slower after nerve transections in older animals.
Arrasate et al. demonstrated that neurons die according to the amount of polyQ protein present within neuronal cells in a dose-dependent but time-independent manner.
Neurotrophic factors are known to promote neuronal survival and regeneration, and when deprivation of retrograde transported neurotrophins occurs, developing neurons die by apoptosis.
We observed a robust neuronal expression of TRE-eGFP in puc mutant embryos; however, not all of these neurons died as suggested by the quantification of DAC-positive neurons.
Whereas we found that inhibition of phagocytosis prevented neuronal loss and left viable neurons, indicating that the neurons must have been viable at the time of their phagocytosis, i.e. the neurons died by phagoptosis.
Specifically, these models may permit the identification of key upstream molecular events that instigate or contribute to neuronal damage, which in turn will provide not only novel insights into the molecular basis of how neuronal cells die but also potential approaches for therapeutic intervention by uniquely targeting mechanisms involved in excitotoxic/neurotoxic signaling cascade.
Although almost half the neuronal cells die by apoptosis during normal brain development, this physiological process may be enhanced under toxic conditions [32].
The current work shows that dJNK signaling, which is active in certain embryonic neurons, normally dying through apoptosis, is able to synchronize excess neuronal death with upregulation of glial phagocytosis of dying neurons.
The detection of dying neuronal cell bodies is much more difficult.
The percentage of the dying neuronal population that could be rescued depended on the time interval between washout of glucose and addition of the pharmacological agents.
