Neurons function

Burgoyne RD, O Callaghan DW, Hasdemir B et al (2004) Neuronal Ca2+-sensor proteins multitalented regulators of neuronal function. Trends Neurosci 27 203-209... 

Gainetdinov RR, Premont RT, Bohn LM et al (2004) Desensitization of G protein-coupled receptors and neuronal functions. Annu Rev Neurosci 27 107—144... 

HIV proteins can also disrupt ion homeostasis in astrocytes, which compromises neuronal function (Pulliam et al. 1993 Benos et al. 1994a, b Holden et al. 1999). Intact HIV-1 virions or gpl20 also markedly inhibit glutamate uptake by astrocytes and cause reductions in excitatory amino acid transporter-2 (EAAT2) mRNA and protein levels (Wang et al. 2003). The inability of astrocytes to buffer extracellular glutamate is likely to decrease the excitotoxic threshold of bystander neurons. 

A substance produced in and released from a neuron to affect some aspect of neuronal function without being transported in the blood. 

Reserpine irreversibly inhibits the triphosphatase that maintains the proton gradient and so it depletes neurons of their vesicular store of transmitter. This explains why restoration of normal neuronal function rests on delivery of new vesicles from the cell bodies. Some amphetamine derivatives, including methylenedioxymethamphetamine (MDMA), are also substrates for the transporter and, as a result, competitively inhibit noradrenaline uptake. Another way of inhibiting the transporter is by dissipation of the pH gradient across the vesicular membrane i-chloroamphetamine is thought to act in this way. 

Neurosteroids differ from nearly all the other transmitters and mediators in that they are lipid-soluble and can easily cross the blood-brain barrier. Thus it is necessary to distinguish those steroids that are produced in the brain from those that find their way there from the circulation after being released from the adrenal cortex or gonads. There are many natural and synthetic steroids that have some effect on neuronal function and can be considered neuroactive but few are actually produced in the brain to act on neurons, i.e. the true neurosteroids. 

These observations, while implicating steroids in brain function and behaviour, cannot be taken as a reliable indicator of their actual effect on neuronal function. Nevertheless, some neurosteroids produce CNS depression with a rapid inhibition of neuronal excitability and one progesterone derivative, alphaxalone (3a-hydroxy-5a pregnane-11, 20 dione, see Fig. 13.5) has been used effectively as an intravenous anaesthetic in humans. 

Approaches (l)-(3) clearly depend on there being some residual neuronal function and... 

To what extent the above approaches can provide successful therapy will depend on both the cause of the disorder and the manner in which the NT is used in normal neuronal function. Thus the disorder could be due to ... 

Figure 16.3 Changes in neuronal function required for the development of epileptic seizures. The factors that may control or induce the changes in neuronal function that turn a normal neuron into a focal one (A) recruit other neurons (focal epileptogenesis) to produce an interictal EEG spike (B) and ensure the spread of activity (general epileptogenesis) to full ictal activity (C) are discussed in the text. They include alterations to various ion channels, especially those for Na, a reduction in local inhibitory activity or an increase in local excitatory drive. The electrophysiological counterparts of some of the events involved are shown in Fig. 16.2...

From this survey it is clear that just as normal neuronal function requires appropriately balanced inhibitory and excitatory controls so the generation of interictal spikes depends on disturbances in both. Clearly activity cannot spread without the activation of excitatory circuits, in which NMDA receptors play an important role, but it will be much facilitated by reduced inhibition (Masukawa et al. 1989). These observations may help to explain the establishment of a focus and the development of the interictal spike, but why activity can only spread to seizure proportions, at certain times, is less clear. It will, however, again require overactivity of excitatory circuits inadequately controlled by inhibitory processes. Since these controls are mediated by... 

Setting aside the general anaesthetics, which do not directly modify the function of any particular neurotransmitter, all the drugs that are used to induce sleep, i.e. the hypnotics , augment the function of GABA and so directly depress neuronal function and probably facilitate cortico-thalamic synchrony. Most of them are benzodiazepines... 

Neurofibrillary tangles are intracellular and consist of abnormally phosphorylated tau protein which is involved in microtubule assembly. Tangles interfere with neuronal function... 

Calahan, M., Molecular properties of sodium channels in excitable membranes, in The Cell Surface and Neuronal Function (Eds C. W. Cotman, G. Poste and G. L. Nicholson), P. I, Elsevier, Amsterdam, 1980. 

Neuronal function depends on a constant supply of oxygen. Hypoxia, a decrease in oxygen availability, depresses neuronal activity. Interruption of blood flow to the brain for only a few seconds leads to unconsciousness. A prolonged lack of blood flow, which is characteristic of stroke, leads to permanent brain damage in the affected area. 

There are several benefits to the presence of this barrier. It protects the neurons of the CNS from fluctuations in plasma components. For example, a change in the potassium ion concentration could alter neuronal function due to its effect on membrane potential. Second, the barrier minimizes the possibility that harmful blood-borne substances reach the CNS. Finally, it prevents any blood-borne substances that could function as neurotransmitters from reaching the brain and causing inappropriate neuronal stimulation. 

Mieda, M., Williams, S. C., Sinton, C. M. et al. (2004a). Orexin neurons function in an efferent pathway of a food-entrainable circadian oscillator in eliciting food-anticipatory activity and wakefulness. J. Neurosci. 24, 10493-501. 

Terwilliger, R.Z., Beitner-Johnson, D., Sevarino, K.A., Crain, S.M., Nestler, E.J. A general role for adaptations in G-proteins and the cyclic AMP system in mediating the chronic actions of morphine and cocaine on neuronal function. Brain Res. 548 100, 1991. 

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