The postnatal development of the benzodiazepine receptor in the cerebral cortex and cerebellum of the rat

Candy, J.M.; Martin, Ian L.

doi:10.1111/j.1471-4159.1979.tb00402.x

Cited by 101 publications

(39 citation statements)

References 13 publications

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“…In conclusion, these experimental results on benzodiazepine binding compare satisfac torily with those previously reported by oth ers [3,4,12,17] and correlate with our obser vations on the ontogenesis of GABA recep tors [1], However, the possibility that differ ent GABA binding sites develop at different rates has been suggested [17,20]; therefore, the effect of GABA on 3H-diazepam binding may be the expression of the development of those GABA recognition sites which corre spond to a modulatory site on 'H-benzodiazepine receptors and probably linked with the psychotropic effect of such agents.…”

Section: Discussionsupporting

confidence: 78%

Ontogeny of <sup>3</sup>H-Diazepam Binding Sites in Different Rat Brain Area

Aldinio¹,

Balzano²,

Savoini³

et al. 1981

Dev Neurosci

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The ontogenesis of the ³H-diazepam binding sites and their modulation by gamma-aminobutyric acid have been studied in different brain areas of rat at various ages, using frozen and two Triton X-100 treated crude synaptic membrane preparations. Benzodiazepine recognition sites are present at birth in all the brain regions investigated and reach adult levels about 3 weeks later. The changes of ³H-diazepam binding with age are due to an increase in the total number of binding sites. In vitro addition of GAB A produces, in newborn and adult cerebral cortex, an increase in affinity, but not in number of binding sites for ³H-diazepam. The effect is age dependent.

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Section: Discussionsupporting

confidence: 78%

Ontogeny of <sup>3</sup>H-Diazepam Binding Sites in Different Rat Brain Area

Aldinio¹,

Balzano²,

Savoini³

et al. 1981

Dev Neurosci

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“…Consistent with our results, functional GABA, receptors are present on Purkinje cells at birth (Woodward et al, 1971) and cerebellar a,-like immunoreactivity on Western blots increases postnatally (McKeman et al, 199 1 a). The increasing postnatal expression of GABA, transcripts in both Purkinje and postmigratory granule cells ((Y,,Pz,& y2,6) is paralleled by increases in GABA, and type I BZ binding after P8 (Coyle and Enna, 1976;Candy and Martin, 1979;Palacios and Kuhar, 1982;Chisholm et al, 1983;Zdilar et al, 1991). An acceleration of BZ binding mainly in the molecular layer between P14 and P28 is probably due to the coincident development of the Purkinje cell dendritic tree (Jacobson, 1978) and extensive production of receptors containing (Y,, p,/&, and yz subunits.…”

Section: Cerebellar Receptorsmentioning

confidence: 98%

“…7, 8; Table 2) predicts the early formation of functional GABA, receptors. Paradoxically, although cortical BZ binding is already substantial at birth (60% of adult; Candy and Martin, 1979;Lippa et al, 1981;Chisholm et al, 1983) and is coupled to GABA, receptors (Palacios et al, 1979;Eichinger and Sieghart, 1986;Kellogg and Pfleger, 1989), the number of rat cortical GABA and muscimol binding sites is low at birth (25% of adult) and increases only after P8 (Coyle and Enna, 1976;Vitorica et al, 1990). The appearance of most cortical GABA, binding coincides with the replacement of perinatal Figure 14.…”

Section: Cortical Receptorsmentioning

confidence: 99%

The distribution of thirteen GABAA receptor subunit mRNAs in the rat brain. III. Embryonic and postnatal development

1992

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The embryonic and postnatal expression of 13 GABAA receptor subunit genes in the rat CNS was studied by in situ hybridization. Each transcript exhibited a unique regional and temporal developmental expression profile. For example, in both embryonic and early postnatal cortex and thalamus, expression of the alpha 2, alpha 3, alpha 5, and beta 3 mRNAs was pronounced. In particular, the alpha 5 gene expression underwent a prominent peak in early brain. Subsequently, the thalamocortical expression of these four genes substantially diminished and was superseded in the adult by the alpha 1, alpha 4, beta 2, and delta subunit mRNAs. Similarly, gamma 1 and gamma 3 gene expression also dropped markedly during development, their initial stronger expression being restricted to relatively few structures. In contrast, gamma 2 gene expression was widespread and mostly remained constant with increasing age. The medial septum and globus pallidus were regions expressing few subunits in both early postnatal and adult stages, allowing clear developmental combinatorial changes to be inferred (alpha 2/alpha 3 beta 2 gamma 2 to alpha 1 beta 2 gamma 2, alpha 2/alpha 3 beta 2 gamma 1 to alpha 1 beta 2 gamma 1/gamma 2, respectively). In contrast, cerebellar Purkinje cells exhibited no developmental switch, expressing only the alpha 1, beta 2, beta 3, and gamma 2 mRNAs from birth to adult. Certain GABAA transcripts were also detected in germinal zones (e.g., beta 1, beta 3, gamma 1) and in embryonic peripheral tissues such as dorsal root ganglia (e.g., alpha 2, alpha 3, beta 3, gamma 2) and intestine (gamma 3). Some parallels in regional and temporal CNS expression were noted (e.g., alpha 1 beta 2, alpha 2 beta 3, alpha 4/alpha 6 delta), whereas the alpha 5 and beta 1 regional mRNA expressions converted over time. The changes of GABAA receptor subunit gene expression suggest a molecular explanation for earlier observations on changing ligand binding affinities. Thus, the composition, and presumably properties, of embryonic/early postnatal rat GABAA receptors differs markedly from those expressed in the adult brain.

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“…As was the case for several other receptors studied in cat visual cortex (Jonsson and Kasamatsu, 1983;Shaw and Cynader, 1985, unpublished observations;Shaw et al, 1984aa;Wilkinson et al, 1983) and the cortex of other species (Candy and Martin, 1979;Pittman et al, 1980), adenosine receptor density (B,d was initially low but increased during postnatal development. 3H-CHA binding density peaked in adulthood, while 3H-NECA binding density peaked at 30 d postnatally.…”

Section: Discussionmentioning

confidence: 69%

Characterization, distribution, and ontogenesis of adenosine binding sites in cat visual cortex

Shaw¹,

Hall²,

Cynader³

1986

J. Neurosci.

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In vitro autoradiographic techniques were used to characterize binding sites for 3H-cyclohexyladenosine (CHA) and 3H-5′-N- ethylcarboxamidoadenosine (NECA) in cat and kitten visual cortex. 3H- CHA binding sites in adult cat have a Bmax of 1,363 fmol/mg protein and a Kd of 6.8 nM. Displacement experiments indicate that 3H-CHA binds to an adenosine receptor similar to the A1-adenosine receptor described by other investigators. 3H-NECA binding sites in adult cat have a Bmax of 518 fmol/mg protein and a Kd of 15.4 nM. Displacement experiments do not allow us to identify this binding site unambiguously. Bmax values increase during postnatal development for both binding sites, peaking in adulthood for 3H-CHA and at 30 d for 3H-NECA. Kd values show neither consistent nor significant differences during postnatal development for either binding site. 3H-CHA and 3H-NECA binding sites are concentrated in layers 1–3 and upper layer 5 in the visual cortex of adult cats. These laminar patterns, however, change during postnatal development, showing the densest binding in the deep cortical layers (5 and 6) in kittens younger than 30 d of age and a fairly homogeneous binding in older kittens before achieving the adult distribution.

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The postnatal development of the benzodiazepine receptor in the cerebral cortex and cerebellum of the rat

Cited by 101 publications

References 13 publications

Ontogeny of <sup>3</sup>H-Diazepam Binding Sites in Different Rat Brain Area

Ontogeny of <sup>3</sup>H-Diazepam Binding Sites in Different Rat Brain Area

The distribution of thirteen GABAA receptor subunit mRNAs in the rat brain. III. Embryonic and postnatal development

Characterization, distribution, and ontogenesis of adenosine binding sites in cat visual cortex

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