Neurons adaptation, mechanisms

Cole RL, Konradi C, Douglass J, Hyman SE (1995) Neuronal adaptation to amphetamine and dopamine molecular mechanisms of prodynorphin gene regulation in rat striatum. Neuron 7 813-823. 

Stress stimuli come in a variety of forms, such as deprivation of trophic factors, ionizing radiation, free radicals (e.g., peroxynitrite), hypoxia, ischemia, heat shock, lipid second messengers (such as ceramide) (Singh et al., 1998), TNF-a, or Fas-ligand. In the brain, neurons are especially susceptible to stress stimuli these stimuli lead to activation of intracellular pathways that either promote apoptosis or defense-adaptation mechanisms. At least three such pathways have been well studied. These pathways lead to the activation of c-Jun N-terminal kinases (JNKs), p38 kinases. 

McAlexander MA, Myers AC, Undem BJ (1999) Adaptation of guinea-pig vagal airway afferent neurones to mechanical stimulation. J Physiol 521(Part 1) 239 7 McAlexander MA, Myers AC, Undem BJ (1998) Inhibition of 5-lipoxygenase diminishes neu-rally evoked tachykinergic contraction of guinea pig isolated airway, J Pharmacol Exp Ther 285(2) 602-7... 

The localization of transporter molecules on the cell surface is dynamic rather than constitutive, such that transport capacity may be adapted to neuronal activity. Obviously, the mechanisms regulating uptake are of principal importance in pharmacology just as pharmacological transport inhibitors can regulate the density of transporters. 

It is easy to speculate that in an active neuron with a rapid firing pattern, the continued release of a peptide may eventually lead to depletion of the peptide occurring. This has been shown in the peripheral nervous system. If this also happens in the CNS it would provide a mechanism whereby the release and resultant receptor effects of a transmitter no longer match the firing pattern and demands of the neuron and so could contribute to long-term adaptations of neurons by a reduction in the time over which a peptide is effective. 

Fig. 11.4. Model for cholinergic signalling in the intestinal mucosa, providing a possible rationale for AChE secretion by parasitic nematodes. ACh released from enteric cholinergic motor neurons stimulates chloride secretion, mucus secretion and Paneth cell exocytosis through muscarinic receptors. Secretory responses may be modulated by mast cell mediators, either directly or via the induction of neural reflex programmes. The role of muscarinic receptor-positive cells in the lamina propria of rats infected with N. brasiliensis is undetermined, as are potential mechanisms of trans-epithelial transport of the enzymes. Adapted from Cooke (1984).

FIGURE 18-9 Several mechanisms through which the substance P gene gives rise to different bioactive peptides in different neurons. Alternative splicing of mRNA leads to translation of distinct precursors, and subsequent processing leads to unique mature peptides. PPT, pre-protachykinin. (Adapted from reference [16].)... 

To complete the list of what we need to know to really understand a cell, there are the issues of adaptive processes—those mechanisms by which cells maintain viability in the face of changing environmental circumstances—and specialized functions that may be unique to a certain cell type such as nerve conduction in neurons. Finally, when we really understand a cell, we will be able to make a definitive mathematical model for it. 

There are several mechanisms whereby antidepressants can modify intracellular events that occur proximal to the posts)maptic receptor sites. Most attention has been paid to the actions of antidepressants on those pathways that are controlled by receptor-coupled second messengers (such as cyclic AMP, inositol triphosphate, nitric oxide and calcium binding). However, it is also possible that chronic antidepressant treatment may affect those pathways that involve receptor interactions with protein tyrosine kinases, by increasing specific growth factor synthesis or by regulating the activity of proinflammatory cytokines. These pathways are particularly important because they control many aspects of neuronal function that ultimately underlie the ability of the brain to adapt and respond to pharmacological and environmental stimuli. One mechanism whereby antidepressants could increase the s)mthesis of trophic factors is... 

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