Cotcha Yankinov
Bluelight Crew
- Joined
- Jul 21, 2015
- Messages
- 2,952
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986775/ - "Developmental Exposure to Terbutaline and Chlorpyrifos, Separately or Sequentially, Elicits Presynaptic Serotonergic Hyperactivity in Juvenile and Adolescent Rats"
"Discussion: In our earlier studies with neonatal terbutaline treatment, we found overexpression of both the 5HT presynaptic transporter and 5HT receptors in adulthood [3]. Notably, however, the primary effects were seen in the regions containing 5HT cell bodies (midbrain, brainstem) and in one area with 5HT terminals, the hippocampus, whereas the cerebral cortex and striatum were largely spared. This pattern is consistent with damage to developing nerve terminals and consequent reactive sprouting [10,32,38] but the persistence of the upregulation of these static markers of 5HT synaptic integrity suggests that underlying functional abnormalities remain.
In the current study, we found initial overall reductions in 5HT content, consistent with nerve terminal damage. This was accompanied by presynaptic 5HT hyperactivity, as monitored by 5HT turnover, throughout juvenile and adolescent stages of development, with the most notable and persistent changes occurring in the cerebral cortex and striatum, the very same regions that appeared to be spared the upregulation of 5HT receptors in our earlier study [3]. The most likely explanation of this pattern is that 5HT synapses are “miswired,” namely that, consequent to the initial damage, sprouting reestablishes innervation but to inappropriate loci within the affected regions, so that presynaptic hyperactivity occurs as compensation for defective synaptic function. Confirmation of this interpretation will require anatomical evaluations; prior work has established that developmental exposures to terbutaline or related β-adrenergic receptor agonists do indeed cause structural alterations consistent with miswiring [33,59] but our findings point to the need to supplement these with specific histological markers to identify the locations and potential misconnections of 5HT projections and their target cells containing 5HT receptors."
"Discussion: In our earlier studies with neonatal terbutaline treatment, we found overexpression of both the 5HT presynaptic transporter and 5HT receptors in adulthood [3]. Notably, however, the primary effects were seen in the regions containing 5HT cell bodies (midbrain, brainstem) and in one area with 5HT terminals, the hippocampus, whereas the cerebral cortex and striatum were largely spared. This pattern is consistent with damage to developing nerve terminals and consequent reactive sprouting [10,32,38] but the persistence of the upregulation of these static markers of 5HT synaptic integrity suggests that underlying functional abnormalities remain.
In the current study, we found initial overall reductions in 5HT content, consistent with nerve terminal damage. This was accompanied by presynaptic 5HT hyperactivity, as monitored by 5HT turnover, throughout juvenile and adolescent stages of development, with the most notable and persistent changes occurring in the cerebral cortex and striatum, the very same regions that appeared to be spared the upregulation of 5HT receptors in our earlier study [3]. The most likely explanation of this pattern is that 5HT synapses are “miswired,” namely that, consequent to the initial damage, sprouting reestablishes innervation but to inappropriate loci within the affected regions, so that presynaptic hyperactivity occurs as compensation for defective synaptic function. Confirmation of this interpretation will require anatomical evaluations; prior work has established that developmental exposures to terbutaline or related β-adrenergic receptor agonists do indeed cause structural alterations consistent with miswiring [33,59] but our findings point to the need to supplement these with specific histological markers to identify the locations and potential misconnections of 5HT projections and their target cells containing 5HT receptors."
