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The expression of GABAA receptor subunits in the substantia nigra is developmentally regulated and region-specific

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Abstract

The substantia nigra pars reticulata (SNR) controls the spread of seizures. GABAAergic drug (agonist or antagonist) infusions into the SNR have age-specific and site-specific effects on flurothyl-induced seizures. Developmental and cell-specific regulation of GABAA receptor subunit expression may be responsible for these specific effects. To test this hypothesis,in situ hybridization was used to examine regional expression of α1 and γ2L GABAA receptor subunit mRNAs in the SNR during development. Distinct temporal and spatial patterns of expression were observed. In rats at postnatal days (PN) 21–60, fewer neurons were labeled with probes directed to α1 and γ2L subunits in SNRanterior compared with SNRposterior. In addition, neurons in SNRanterior contained higher amounts of hybridization grains than in SNRposterior. In PN 15 rats, the labeling of neurons was relatively diffuse throughout the anterior and posterior SNR regions with moderate amounts of hybridization grains for both subunits. The finding of age-related differential distribution of α1 and γ2L subunit mRNAs in the SNR suggests that GABAA receptor heterogeneity may play a role in the age-specific and site-specific effects of GABAAergic agents on seizures in the SNR.

Sommario

La sostanza nera pars reticulata (SNR) controlla la propagazione delle crisi. Infusioni di GABA agonisti o antagonisti nella SNR hanno effetti specifici in rapporto all’età e alla sede sulle crisi indotte con flurothyl, per la probabile influenza di fattori regolatori dell’espressione di subunità del receptore GABAA specificamente legati allo sviluppo e al tipo cellulare. L’ipotesi è stata verificata ana-lizzando l’ espressione regionale del mRNA delle subunità recettoriali GABAA α1 e γ2L durante lo sviluppo. Diverse modalità di espressione temporale e spaziale sono state osservate. Nel ratto ad una età postnatale (PN) di 21–60 giorni, il numero di neuroni marcati con sonde dirette alle subunità α1 e γ2L è risultato inferiore rispetto alla posteriore. Inoltre, i neuroni di SNR anteriore contenevano una quantità più elevata di granuli di ibridizzazione rispetto a quelli di SNR posteriore. In ratti PN 15, invece, la marcatura di neuroni è risultata relativamente diffusa nell’ambito delle regioni anteriori e posteriori di SNR con una quantità moderata di granuli di ibridizzazione per entrambe le subunità.

Il rilievo di una distribuzione differenziale età dipendente dell’mRNA delle subunità α1 e γ2L nella SNR suggerisce che un’eterogeneità recettoriale possa giocare uno specifico ruolo nel determinare gli effetti età e sito-specifici sulle crisi di agenti GABAergici iniettati nella SNR.

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Authors and Affiliations

  1. Department of Neurology K312, Albert Einstein College of Medicine, 1410 Pelham Parkway South, 10461, Bronx, NY, USA

    J. Veĺišková, E. F. Sperber & S. L. Moshé

  2. Institute of Physiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, 142 20, Prague 4, Krc, Czech Republic

    H. Kubová

  3. Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA

    E. F. Sperber, S. L. Moshé, L. K. Friedman, R. Wu & R. S. Zukin

  4. Department of Pediatrics, Albert Einstein College of Medicine and Einstein/Montefiore Epilepsy Center, Bronx, NY, USA

    S. L. Moshé

Authors
  1. J. Veĺišková
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  2. E. F. Sperber
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  3. S. L. Moshé
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  4. H. Kubová
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  5. L. K. Friedman
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  6. R. Wu
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  7. R. S. Zukin
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Veĺišková, J., Sperber, E.F., Moshé, S.L. et al. The expression of GABAA receptor subunits in the substantia nigra is developmentally regulated and region-specific. Ital J Neuro Sci 19, 205–210 (1998). https://doi.org/10.1007/BF02427602

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  • DOI: https://doi.org/10.1007/BF02427602

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