Transport systems astrocytes

Histamine is stored within and released from neurons but a neuronal transporter for histamine has not been found. Newly synthesized neuronal histamine is transported into TM neuronal vesicles by the vesicular monoamine transporter VMAT2 [16]. Both in vivo and in vitro studies show that depolarization of nerve terminals activates the exocytotic release of histamine by a voltage- and calcium-dependent mechanism. Once released, histamine activates both postsynaptic and presynaptic receptors. Unlike the nerve terminals from other amine transmitters, however, histaminergic nerve terminals do not exhibit a high-affinity uptake system for histamine [5, 9, 23]. Astrocytes may contain a histamine transport system. 

Epilepsy is an example of excessive neural signaling in the central nervous system. Relative cellular and extracellular space (ECS) volume has been demonstrated to play an important role in the propensity for epileptic seizures. For example, reducing ECS volume by exposure to hypotonic medium produces hyperexcitability and enhanced epileptiform activity, whereas hyperosmolar medium reduces excitability. The hypothesis that AQP4-dependent water transport in astrocytes might modulate intrinsic brain excitability was tested by seizure susceptibility in response to the GABAa antagonist convulsant pentylenetetrazol... 

Figure 7.44 The metabolism and toxicity of MPTP. Diffusion into the brain is followed by metabolism in the astrocyte. The metabolite MPP+ is actively transported into the dopaminergic neuron by DAT. It is accumulated there and is actively taken into mitochondria by another uptake system. Here, it inhibits mitochondrial electron transport between NADH dehydrogenase (NADH DHase) and coenzyme Q (Q10). Consequently, it blocks the electron transport system, depletes ATP, and destroys the neuron. Abbreviations MPTP, 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine DAT, dopamine transporter uptake system.

Astrocytes undergo rapid swelling in certain acute pathological conditions like ischemia and traumatic brain injury. Different mechanisms are involved in such swelling process of astrocytes. Some of these are, decreasing extracellular fluid osmolality, intracellular acidosis, formation of ammonia, increase in Na", K", 2CT co-transporter system, and due to drastically... 

A widespread early reponse by astrocytes is that they demonstrate swelling and cytoplasmic lucency within minutes of reduction in CBF.1416 However, there is increasing evidence that the microglial response (see below) precedes or at least parallels that of astrocytes. The most notable response by astrocytes occurs in perivascular foot processes (Figure 2.1), possibly related to the high concentration of transport systems in the membranes of these processes. Swollen astrocyte foot processes demonstrate a lucent cytoplasm lacking arty content of cytoplasmic... 

Na+-independent and also Na+-dependent GSH transport systems have been found in lens epithelium, retinal Muller cells, brain endothehal cells and astrocytes [82-84]. The Na+-dependent transport mediates GSH uptake,whereas the Na+-independent carrier appears to be mainly involved in GSH efflux. It is worth noting that these transport systems allow GSH transport across the blood-brain barrier in vivo [85]. 

Blondeau, J. P., Beslin, A., Chantoux, F., and Francon, J., Triiodothyronine is a high-affinity inhibitor of amino acid transport system LI in cultured astrocytes, /. Neurochem., 60, 1407, 1993. 

Aschner, M., Eberle, N., Goderie, S., et al., 1990. Methylmercury uptake in rat primary astrocyte cultures the role of the neutral amino acid transport system. Brain Res. 521, 221—228. 

The lipid compositions of plasma membranes, endoplasmic reticulum and Golgi membranes are distinct 26 Cholesterol transport and regulation in the central nervous system is distinct from that of peripheral tissues 26 In adult brain most cholesterol synthesis occurs in astrocytes 26 The astrocytic cholesterol supply to neurons is important for neuronal development and remodeling 27 The structure and roles of membrane microdomains (rafts) in cell membranes are under intensive study but many aspects are still unresolved 28... 

Numerous modifications of in vitro culture systems have been developed for the estimation of BBB transfer [52]. Culture systems in use are either primary cultures of brain microvessel endothelial cells (BMEC) or immortalized endothelial cell hues. BMEC may be grown in co-culture with astrocytes or in astrocyte-conditioned medium. Astrocyte-derived factors increase the tightness of the barrier as measured by transendothelial electrical resistance (TEER) and by the permeability of hydrophUic markers such as sucrose. They also up-regulate the expression of BBB-enriched enzymes such as y-glutamyl transpeptidase (y-GTP) and alkaline phosphatase. A setup of the in vitro technique in a transwell system for transport studies is depicted in Figure 2.5. 

MPTP is a molecule, which is sufficiently lipophilic to cross the blood-brain barrier and enter the astrocyte cells. Once in these cells, it can be metabolized by monoamine oxidase B to MPDP and then MPP both of which are charged molecules. These metabolites are therefore not able to diffuse out of the astrocyte into the bloodstream and away from the brain. However, the structure of MPP allows it to be taken up by a carrier system and concentrated in dopaminergic neurones. In the neurone, it inhibits the mitochondrial electron transport chain leading to damage to the neurone. 

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