Long developing brain

The long-term effects of SSRI medications on the developing brain remain to be explored. A preliminary study on developing rodent brains reported a persistent increase in serotonin transporter density in the frontal... 

Considerations such as these have helped move contemporary thinking toward an evolutionary view.488 489 495-499 If the mortality of an animal in the wild (extrinsic mortality) is high it will evolve to have rapid development, good reproductive ability, and a short lifetime. If the extrinsic mortality is low the lifetime will be long. Such animals will require development of good protective functions including a highly developed brain. 

LONG-TERM EFFECTS OF CHEMICALS ON DEVELOPING BRAIN AND BEHAVIOR M. MIRMIRAN and S. DE BOER... 

Generally, according to high-dose exposure studies, animals exposed to nerve agents that exhibit seizures that are not promptly controlled develop brain damage and subsequent neurobehavioral problems. Animals that do not develop seizures or those that are rapidly and effectively treated with drugs that stop the seizures suffer no brain lesion and display no long-term neurobehavioral deficits. 

Depression is serious not only because of the effects it has on the developing brain, but it can also have long-lasting social repercussions. Teenagers who are depressed are more likely to have problems with crime or substance abuse (Figure 7.3). 

The developing brain accumulates long-chain (C20 and C22) polyenoic fatty acids, particularly during cell division (Crawford Sinclair, 1972 Sinclair Crawford, 1972). Vz novo synthesis of these acids does not occur in higher animals and they are derived either directly from food or by metabolism from the parent essential fatty acids, linoleate and a-linolenate. 

It seemed that the degree of brain and nervous system development was somehow related to the availability of long-chain poly-enoates to the developing brain. 

The results demonstrate that the fetus is not simply dependent on maternal food intake, but that both placenta and fetus actively reprocess the essential fatty acids with the result that long-chain polyenoic acids are incorporated into the developing brain lipids. Although this process is clearly of great importance to brain development, the conversion of a —linolenic acid to docosahexaenoic acid is slow. A low desaturation rate of parent essential fatty acids is consistent with the Zn )iXKO studies reported by Professor Brenner and Dr. Sprecher earlier in this conference and with our iyi )AJ00 observations in the rat (Hassam, Sinclair Crawford, 1975 Hassam Crawford, 1976 Hassam, Rivers Crawford, 1976). In the cat the desaturase was not detected (Rivers, Sinclair Crawford, 1975) iyi )lvo. 

The rate of accumulation of PUFA in the developing brain (Sinclair Crawford, 1972), the formation from the precursors in the CNS (Mead, 1976), the passage from the blood through the blood-brain barrier (Dhopeshwarkar Mead, 1969 1970) and the incorporation into brain lipids of both the short-chain unsaturated precursors (linoleic and linolenic acids) and the long-chain polyunsaturated derivatives (arachidonic and docosahexaenoic acids) following oral administration (Sinclair, 1975), have been studied in detail. 

In parallel with the identification of distinct transporters for GABA there has been continued interest in the development of selective blockers of these transporters and the therapeutic potential that could result from prolonging the action of synaptically released GABA. It has been known for a long time that certain pro-drugs of nipecotic add (e.g. nipecotic acid ethyl ester) are able to cross the blood-brain barrier and are effective anticonvulsants in experimental models of epilepsy. More recently, several different systemically active lipophillic compounds have been described that act selectively on GAT-1, GAT-2 or GAT-3 (Fig. 11.4). Of these, tiagabine (gabitiil), a derivative of nipecotic acid that acts preferentially on GAT -1, has proved clinically useful in cases of refractory epilepsy. 

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