An autoradiographic study of the prenatal development of benzodiazepine- binding sites in rat brain

Schlumpf, Margret; Richards, J. G.; Lichtensteiger, W.; Möhler, Hanns

doi:10.1523/jneurosci.03-07-01478.1983

Cited by 93 publications

(35 citation statements)

References 18 publications

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“…On the other hand, MS binding in rat cortex still was less than 10% at P2d, while FZ binding had reached 50% of adult (Palacios et al, 1979). The only study using autoradiographic methods to determine prenatal laminar developmental patterns is that of Schlumpf et al (1983); postnatal ages were not included. They find a rostral-caudal developmental gradient for FZ binding in that labeling appeared in frontal cortex at F16d but did not reach occipital cortex until F2 1 d. At F 16d, only the marginal zone or future layer 1 was labeled, but by F18d the subplate and/or layer 6 was also labeled.…”

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confidence: 99%

Pre- and postnatal development of GABA receptors in Macaca monkey visual cortex

et al. 1991

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GABA is a putative inhibitory neurotransmitter in adult mammalian visual cortex but also has been implicated as playing a crucial role in cortical information processing during development. In order to understand better the role of GABA during primate visual cortex development, we have examined the time course of GABAA and GABAB receptor ontogenesis in 18 Macaca nemestrina monkeys ranging from fetal day 61 (F61d) to adulthood. The GABA and benzodiazepine binding sites of the GABAA receptor were detected by 3H-muscimol (3H-MS) and 3H- flunitrazepam (3H-FZ), respectively. GABAB receptors were detected by 3H-baclofen (3H-BA). All ligands were visualized by in vitro autoradiography. Quantitative analysis of film density was done to compare laminar changes during pre- and postnatal development. Saturation binding experiments were done for MS and FZ binding sites to determine receptor number (Bmax) and affinity (Kd) at selected pre- and postnatal ages. Both MS and FZ binding sites were present at F61d-72d throughout the cortical plate and marginal zone. FZ binding sites were more dense than MS binding sites over the cortical plate at young ages and were especially dense over the marginal zone. FZ binding sites also were present in lesser amounts over the subplate and intermediate zone, but not over the subventricular zone. By F119d-126d, layer 4 could be distinguished by its higher density for both ligands. The basic adult laminar pattern was established for both MS and BZ binding sites by birth (birth = F165d-170d). After birth, MS density increases dramatically in all layers, but layer 4C remains most dense to adulthood. FZ labeling is heavy in both layers 4 and 3 at birth but after 4 weeks after birth (P4 wk) it declines somewhat in the supragranular layers so that layer 4C now predominates. Labeling in layers 5/6 virtually disappears after birth. BA binding sites were present at F126d, at which time layer 4 was slightly lighter than the remainder of striate cortex; this laminar pattern remained basically the same throughout our series to adulthood. Competitive binding of agonist and antagonists for the GABAA receptor showed that MS binding characteristics were similar at F126d and P8.5 years (yr). MS binding site Bmax was about 8% of adult values at F72d, 24% by F126d, and 56% at F152d. Bmax then rose rapidly after birth to peak at P18wk at 169% of adult values, and then declined to P1yr. A second peak of 143% was found around P3.5yr, with adult values reached by P8.5yr.(ABSTRACT TRUNCATED AT 400 WORDS)

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confidence: 99%

Pre- and postnatal development of GABA receptors in Macaca monkey visual cortex

et al. 1991

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“…Central type benzodiazepine binding sites were analyzed using [3H]flunitrazepam as previously described by Schlumpf et al (13). The assay was carried out by incubating the brain sections for 40 min at 4°C in 50 mM TrisHCl buffer (pH 7.4) containing 100 mM NaCl and 1 nM [3H] flunitrazepam (2.85 TBq/mmol; Commissariat a 1'Energie Atomique, Saclay, France).…”

Section: Methodsmentioning

confidence: 99%

“…In the rat brain, benzodiazepine binding sites are detectable as early as the 14th d after conception (13). At birth, these receptors are present at a relatively high density and they reach adult levels about 3 wk later.…”

Section: Development Of Central Benzodiazepine Receptorsmentioning

confidence: 99%

Autoradiographic Changes in Central Benzodiazepine Binding Sites and Their Coupling to γ-Aminobutyric Acid Receptors after Seizures in the Developing Rat

Werck

Daval

1991

Pediatr Res

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ABSTRACT. Benzodiazepines are psychoactive substances classically used for their anticonvulsant properties in neonates as well as in adults. In a previous work, we have shown that seizures lead to an age-dependent upregulation of central benzodiazepine binding sites measured in isolated rat cerebral membranes. However, information concerning regional changes in the receptor density was lacking. In our present study, the effects of bicuculline- GABA, y-aminobutyric acidNumerous neuropathologic studies have pointed out that during the neonatal period and early infancy, epileptic manifestations are relatively frequent, with peculiar characteristics. Children are more susceptible to epileptic brain damage than adults (I), and recurrent or prolonged seizures in infants and children may be followed by major neurologic sequelae (2).Benzodiazepines are psychoactive drugs with anxiolytic, anticonvulsant, and muscle relaxant properties that are widely prescribed in neonates as well as in adults (3). The mechanism of benzodiazepine central action has been attributed to a highaffinity, saturable, and specific binding site and its interaction with a GABA-regulated chloride channel (4, 5). In animals,

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“…While actions of BDZ on the fetal central nervous system may be mediated by centraltype BDZ-binding sites on -aminobutyric acid type A receptors (GABA A receptors) (Schlumpf et al 1983(Schlumpf et al , 1995, the peripheral BDZ receptor (PBR), which is expressed by a majority of fetal tissues (Bürgi et al 1999), might represent a site of action of BDZ on developing non-neural structures such as immune and endocrine systems. The PBR, which binds BDZ and isoquinoline carboxamide derivatives, has been localized to the outer mitochondrial membrane and cell membrane (Woods et al 1996, Papadopoulos et al 1997.…”

Section: Introductionmentioning

confidence: 99%

Diazepam-binding inhibitor/acyl-CoA-binding protein mRNA and peripheral benzodiazepine receptor mRNA in endocrine and immune tissues after prenatal diazepam exposure of male and female rats

Bürgi

Lichtensteiger²,

Schlumpf

2000

Journal of Endocrinology

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Peripheral benzodiazepine (BDZ) receptor (PBR) and diazepam-binding inhibitor/acyl-CoA-binding protein (DBI/ACBP) characterized as a ligand at central BDZ receptors, at PBR with involvement in the regulation of steroidogenesis, and as an intracellular acyl-CoA transporter, are both known to interact with BDZ in adult systems. We investigated their expression after prenatal exposure to BDZ. Diazepam (1·25 mg/kg per day s.c.) was administered to time-pregnant Long Evans rats from gestational day (GD) 14 to 20. Expression of mRNAs encoding for PBR and for DBI/ACBP was studied in the same animals with 33 P-labeled 60 mer oligonucleotides (oligos) by in situ hybridization at GD20, and with 32 P-labeled oligos by Northern blot in steroidogenic and immune organs at postnatal day (PN) 14 and in adult offspring. Prenatal diazepam increased DBI/ACBP mRNA expression in male fetal adrenal and in fetal and PN14 testis. Thymus exhibited increased DBI/ACBP mRNA in male fetuses and in adult female offspring, and reduced organ weight at PN14 in both sexes. In female spleen, an increase in DBI/ACBP mRNA and a decrease in PBR mRNA was seen at PN14. Apart from the finding in spleen, no drug-induced changes in PBR mRNA were observed. The effects of prenatal diazepam were superimposed on treatment-independent sex differences in DBI/ACBP mRNA and PBR mRNA expression. Our data indicate that expression of DBI/ACBP mRNA in steroidogenic and immune organs can be affected by exposure to BDZ during ontogeny, while PBR mRNA expression appears to be less sensitive. They further reveal marked sex differences in the developmental patterns of the two proteins during pre-and postpubertal ontogeny.

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An autoradiographic study of the prenatal development of benzodiazepine- binding sites in rat brain

Cited by 93 publications

References 18 publications

Pre- and postnatal development of GABA receptors in Macaca monkey visual cortex

Pre- and postnatal development of GABA receptors in Macaca monkey visual cortex

Autoradiographic Changes in Central Benzodiazepine Binding Sites and Their Coupling to γ-Aminobutyric Acid Receptors after Seizures in the Developing Rat

Diazepam-binding inhibitor/acyl-CoA-binding protein mRNA and peripheral benzodiazepine receptor mRNA in endocrine and immune tissues after prenatal diazepam exposure of male and female rats

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