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Biomedical subjects

E C Azmitia

Publications and source records attributed to E C Azmitia.

At least 73 records · Page 4Linked to original sources
PubMed1991

Differential effects of prenatal and postnatal ACTH or nicotine exposure on 5-HT high affinity uptake in the neonatal rat brain.

These studies were designed to examine the differential effects of prenatal or postnatal administration of ACTH 1-39 and nicotine, on 5-HT high affinity uptake in brainstem and hippocampal synaptosomes. ACTH was administered prenatally (to pregnant dams) and postnatally to the neonates. Postnatal administration of ACTH significantly increased high-affinity 5-HT uptake in the hippocampus and especially the brainstem at both 7 and 21 days after birth. Prenatal ACTH, on the other hand, transiently increased 5-HT uptake in only the brainstem at 7 days, a change that was reversed at 21 days. While the effects of postnatal nicotine administration were essentially the same as those of postnatal ACTH treatment, prenatal nicotine, unlike ACTH, did not alter 5-HT uptake in 7-day-old rats but did reduce uptake in both tissues at 21 days. The observation that postnatal nicotine mimics the effects of postnatal ACTH and that nicotine stimulates ACTH release, suggests that the postnatal effects of nicotine may be exerted through ACTH.

Adrenocorticotropic Hormone↗
PubMed1991

Awakening the sleeping giant: anatomy and plasticity of the brain serotonergic system.

The serotonergic neurons of the mammalian brain comprise one of the most expansive chemical systems known. The cell bodies are largely confined to the midline (raphe) region of the brain stem in two general clusters: a superior group that consists of the dorsal raphe nucleus (B-7 and B-6), median raphe nucleus (B-8 and B-5), caudal linear nucleus (rostral B-8), and supralemniscal nucleus (B-9), and an inferior group that consists of nucleus raphe obscurus (B-2), nucleus raphe pallidus (B-1), nucleus raphe magnus (B-3), ventral lateral medulla (B-1/B-3), and the area postrema. The axons from these cells project throughout the neuroaxis from the spinal cord to the olfactory bulb and from the cerebral cortex to the hypothalamus. The development of this giant system begins very early in gestation and is influenced by a variety of growth regulatory factors, including the astroglial protein S-100 beta. Evidence will be presented that the serotonergic system plays a major role in the maturation of the brain by interacting with the 5-HT1A receptors which are most dense during these early developmental periods. The 5-HT1A receptor is located on both neurons and astrocytes, and in the latter cells may serve to stimulate release of S-100 beta. The developmental role of 5-HT appears to become dormant as the brain matures, and during aging and Alzheimer's disease, 5-HT receptors are significantly depressed. However, specific damage to 5-HT fibers in the adult brain by 5,7-dihydroxytryptamine produces a sharp fall in the levels of 5-HT which seems to reactivate the developmental signals in the brain. Not only are the serotonergic fibers encouraged to sprout and expand their territory, but the stimulation of the astrocytic growth factor by a 5-HT1A agonist is reinstated. The ability to recall developmental processes in the adult brain by interrupting the 5-HT fibers may provide important tools for understanding and treating the aged brain.

Adult↗
PubMed1990

Effects of 5,7-dihydroxytryptamine injections in the fornix-fimbria on locomotor activity in photocell cages and the open field.

Microinjections of 5,7-dihydroxytryptamine (5,7-DHT) into the fornix-fimbria (FF) reduced dorsal hippocampal [3]5-HT uptake to 40% of control levels. The FF 5,7-DHT lesions increased nocturnal activity in photocell cages, but reduced central ambulation in diurnal open field tests. The lesions also disrupted both habituation of rearing across days in the open field and alternation in a Y-maze. Hence FF-derived hippocampal 5-HT terminals participate in controlling activity, but their role depends on the test apparatus and procedures.

5,7-Dihydroxytryptamine↗
PubMed1990

Stimulation of astroglial 5-HT1A receptors releases the serotonergic growth factor, protein S-100, and alters astroglial morphology.

Stimulation of astroglial 5-HT1A receptors causes astroglial cells to acquire a more mature morphology and to release a factor (or factors) which promotes growth of serotonergic neurons. By using an antibody-blocking approach, we have shown that at least one of the growth-promoting factors thus released is the astroglial-specific protein S-100. This may be a particularly important observation, in view of studies implicating S-100 in both Down's syndrome and Alzheimer's disease.

Animals↗
PubMed1990

Enhanced spatial discrimination learning in rats following 5,7-DHT-induced serotonergic deafferentation of the hippocampus.

Learning in rats trained in the Stone 14-unit T-maze, a complex, positively reinforced spatial discrimination task was assessed following cytotoxic (5,7-dihydroxytryptamine; 5,7-DHT) deafferentation of the serotonergic inputs to the hippocampus. Serotonergic deafferentation was accomplished by infusing the cytotoxin in to the fornix-fimbria/cingulum bundle. Lesioned rats reached criterion (i.e. learned) in significantly fewer trials and made significantly fewer errors throughout training than either vehicle-injected or sham-operated controls. This represents the first time that the effects of selective chronic destruction of serotonergic inputs to the hippocampus have been investigated. The present results provide, therefore, evidence in support of a neuromodulatory role for serotonin (5-HT) within the rat hippocampus in the mediation of the processes underlying learning and memory for this task. Other studies are, therefore, warranted in order to determine whether hippocampal 5-HT also plays a role in the mediation of the processes underlying learning and memory in other types of tasks.

5,7-Dihydroxytryptamine↗
PubMed1990

S-100B but not NGF, EGF, insulin or calmodulin is a CNS serotonergic growth factor.

The effects of S-100B, nerve growth factor (NGF), epidermal growth factor (EGF) and insulin were tested in cultured mesencephalic neurons. Only chronic S-100B showed enhancement (maximal at 3.2 ng/ml is 171%) after 3 days of incubation of the [3H]5-HT uptake capacity by serotonergic neurons. A single application at initial plating of S-100B (maximal at 5 ng/ml is 185%), but not calmodulin, increased the development of the [3H]5-HT uptake capacity by the cultured serotonergic neurons. Morphometric analysis of cultured 5-HT immunoreactive (IR) neurons showed an increase (135 and 147%) in neurite length 30 h after S-100B application of 16 and 3.2 ng/ml (respectively). These results suggest that S-100B is a serotonergic growth factor in the mammalian brain.

Animals↗
PubMed1990

MDMA (ecstasy) effects on cultured serotonergic neurons: evidence for Ca2(+)-dependent toxicity linked to release.

Animal studies have established a correlation between release of 5-hydroxytryptamine (5-HT) and the long-term reduction of 5-HT (toxicity) by 3,4-methylenedioxymethamphetamine (MDMA) with the S(+) enantiomer being more active than the R(-). Using a microculture system of fetal raphe neurons, the enantiomers of MDMA were tested to determine if a similar difference in potency existed. The results showed that the development of the uptake capacity of [3H]5-HT in 4-day cultures was half-maximally inhibited by a single application at time of plating of 5 X 10(-6) M S(+)-MDMA and 5 X 10(-5) M R(-)-MDMA. In order to determine if the Ca2(+)-independent release (chemically induced through the transporter protein and inhibited by reuptake blockers) or the Ca2(+)-dependent release (K(+)-induced and inhibited by presynaptic receptors) contributed to the toxicity, fluoxetine and D1 and alpha 2 agonists were studied. The results showed that both forms of release were involved in the loss of [3H]5-HT uptake capacity, with the direct MDMA-induced Ca2(+)-independent (fluoxetine-sensitive) release being the first step. Evidence from binding studies indicates that MDMA has a micromolar affinity for the 5-HT2 receptor, and our studies in culture showed that ketanserin, a specific 5-HT2 antagonist, was effective at attenuating the effects of S(+)-MDMA on the development of the [3H]5-HT uptake capacity by the cultured raphe neurons. The 5-HT2 receptor is linked to increased intracellular Ca2+ through a second messenger phosphatidylinositol (PI)-hydrolysis mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Methylenedioxyamphetamine↗
PubMed1990

Neurotrophic factor for serotonergic neurons prevents degeneration of grafted raphe neurons in the cerebellum.

Earlier studies in this laboratory have shown that partial serotonergic (5-HT) deafferentation from the hippocampus induced a homotypic sprouting. The 5-HT-denervated hippocampus was further found to be a favorable environment for the growth of grafted 5-HT, but not for norepinephrinergic neurons. In the current study, we have extracted a trophic factor in the denervated hippocampus with hypotonic solution in high-speed supernatant fraction. The trophic extract was assayed in a unique experimental paradigm--test the growth of grafted 5-HT neurons in the cerebellum, which receives the least 5-HT innervation, and where grafted 5-HT neurons have seldom survived. The diluted trophic extract (1:200) produced a dramatic increase in (a) the survival rate, (b) the 5-HT fiber-density, and (c) the 5-HT and 5-hydroxyindoleacetic acid levels of grafted 5-HT neurons in the cerebellum. In addition, Nissl-counterstaining showed that the size of the grafted raphe also apparently increased. The concentrated trophic extract (1:1) did not increase the survival rate of the grafted raphe neurons. These results indicate that (a) the supernatant in the 5-HT-denervated hippocampus contains a potent neurotrophic factor to 5-HT neurons (b) which can either directly or indirectly also support non-5-HT raphe neurons, and (c) possibly an inhibitory factor is present which is detrimental to 5-HT neurons in high concentration.

Animals↗
PubMed1990

Neuropeptides as positive or negative neuronal growth regulatory factors: effects of ACTH and leu-enkephalin on cultured serotonergic neurons.

In summary, we have presented evidence that neuropeptides can function as either positive or negative growth regulatory factors during development. The ACTH family of peptides appear to act predominantly as a positive growth regulatory factor-enhancing neurite outgrowth, cell survival, biochemical maturation and behavioral expression. These effects of ACTH are most pronounced prior to the time the afferent cell has reached its target. Thus, ACTH may act as a low level general neurotrophic growth regulatory factor. The opioids have the opposite effect. These neuropeptides inhibit neurite extension, cell survival, and biochemical maturation. The effects of these negative growth regulatory factors are observed even when the afferents have reached their targets. The action of the opioids is thought to occur through specific receptors and known second messenger systems. Thus, CNS neuropeptide levels can have important actions in regulating the development of a variety of CNS systems, and permanently influencing the structure and function of the brain.

Adrenocorticotropic Hormone↗
PubMed1989

Physiological effects of selective 5-HT1a and 5-HT1b ligands in rat hippocampus: comparison to 5-HT.

The responses of CA1 neurons to topical application of serotonin (5-HT) and selective 5-HT1a and 5-HT1b agonists were examined with intracellular recording in the hippocampal slice. 5-HT produced a uniform hyperpolarizing response associated with an increase in K conductance as previously reported. In addition a marked reduction was recorded in slow afterhyperpolarization (AHP) which follows a burst discharge. 8-OH-DPAT, ipsapirone and LY165,163 partially mimicked the hyperpolarizing response to 5-HT when first applied to the slice. However, these 5-HT1a ligands antagonized responses to subsequent applications of 5-HT. Topical application of the 5-HT1b ligand TFMPP on the slice did not produce the direct or antagonistic action seen with the 5-HT1a ligands. It is suggested that the physiological response to 5-HT in the rat hippocampus is mediated by a 5-HT1a receptor. The currently available 5-HT1a ligands show a low agonist potential and a high antagonist action towards the responses of hippocampal neurons to 5-HT. Definite classification of the hyperpolarizing response to 5-HT awaits development of more specific ligands having a pure agonistic activity.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1989

Stimulation of astroglial serotonin receptors produces culture media which regulates growth of serotonergic neurons.

Our work has been concerned with the role of high affinity serotonin receptors in regulating the development of the serotonergic system. In previous studies, we have found evidence that these receptors occur on astroglial cells and that their number is developmentally linked. The current work is aimed at investigating the mechanism by which these receptors may regulate serotonin neuronal growth. Primary cultures of astroglial cells were exposed to serotonin (5-HT) or the selective receptor agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-D-PAT, for 5-HT1a receptors) or trifluoro-methyl-phenyl-piperazine (TFMPP) and m-chlorophenylpiperazine (mCPP) (for 5-HT1b receptors). Media was collected after 4 or 24 h, and added to primary cultures of serotonergic neurons. Growth was determined by specific uptake of radiolabeled serotonin into the cultures. Our results show the presence of a factor(s) in the glial-conditioned media which can be stimulatory or toxic to serotonin neurons, depending on the neuronal plating density. This factor is significantly present after 24 h, is found in both brainstem and cortical astroglial-conditioned media and appears to be linked to the 5-HT1a receptor. Thus, it appears possible that the serotonergic neuronal system can regulate its own development through an action on astroglial cells.

Animals↗
PubMed1989

Effects of acute and chronic administration of Leu-enkephalin on cultured serotonergic neurons: evidence for opioids as inhibitory neuronal growth factors.

Leu-enkephalin, at concentrations between 18 microM and 1.8 pM, was administered in a single or daily dose to dissociated mesencephalic raphe cell cultures maintained for 3 or 5 days. Daily administration of Leu-enkephalin produced an inhibition of high affinity uptake of [3H]5-HT, a measure of serotonergic process outgrowth in cultures of fetal neurons. This inhibition was maximal at a dose of 18 nM in both 3 (59%, P less than 0.05)- and 5 (38%, P less than 0.05)-day cultures. The expression of uptake was consistently lower in 5-day cultures than in 3-day cultures at all concentrations tested. In marked contrast, a single dose of Leu-enkephalin at the time of plating stimulated uptake in 3- and 5-day cultures. Maximal stimulation was observed at 180 nM for both 3 (191%, P less than 0.05)- and 5 (140%, P less than 0.05)-day cultures. The results obtained after a single dose of the opioid may reflect a paradoxical stimulation probably due to a rebound mechanism of receptors since co-administration of bacitracin (0.5 mg/ml), an aminopeptidase inhibitor, resulted in inhibition of the uptake expression. Together these results indicate that Leu-enkephalin can function as an inhibitory regulatory growth factor for neuronal cultures when constant exposure to this opioid is maintained over time.

Aminopeptidases↗
PubMed1988

Transplanted raphe and hippocampal fetal neurons do not displace afferent inputs to the dorsal hippocampus from serotonergic neurons in the median raphe nucleus of the rat.

To determine if fetal transplants can substitute for or suppress intrinsic serotonergic (5-HT) innervation, we studied the relationship between transplanted and the endogenous raphe neurons projecting to the hippocampus. Fetal raphe transplants produced a 5-HT hyperinnervation of dorsal hippocampus in adult rats. Yet, transplants of fetal raphe tissue did not affect the number of median raphe nucleus (MRN) neurons, approximately 300, which retrogradely transported HRP from the hippocampus. This provides evidence that transplanted 5-HT neurons can co-exist with intrinsic 5-HT nerve terminals in the target area for at least one month. In the second part of this study, fetal hippocampal tissue was transplanted into the host hippocampus. Intrinsic 5-HT immunoreactive fibers innervated the transplanted fetal tissue. Nevertheless, the number of MRN neurons innervating the host tissue as revealed by HRP retrograde transport remained unchanged. Changes in the innervation pattern and 5-HT level in the dorsal hippocampus occur following transplantation of fetal tissue. These changes are discussed and suggest that both the target tissue and afferent neurons readjust to accommodate extrinsic transplanted tissue.

Animals↗
PubMed1988

Effects of prenatal 5-methoxytryptamine and parachlorophenylalanine on serotonergic uptake and behavior in the neonatal rat.

Parachlorophenylalanine (pCPA) or 5-methoxytryptamine (5MT) was administered to pregnant Sprague Dawley rats from day 8 (D8) of gestation till D17 and from D12 until birth respectively. Birth weights of both drug groups of neonates were approximately 20% less than the saline-injected controls. 5MT neonates showed a significant reduction of high affinity 3H-5HT uptake in the brainstem at all three time points: D1, D15, D30, and a slight reduction in the forebrain reaching significance only on D30. The pCPA animals showed a significant reduction in the brainstem and forebrain on D1 and D30, but only a small nonsignificant reduction in both areas on D15. Behaviors measured on day 15 revealed that in general activity, spontaneous alternation, and passive avoidance both drug groups of neonates showed deficits: less activity, less alternation, and less avoidance.

5-Methoxytryptamine↗