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Neuroscience. 2011 Dec 29;199:133-42. doi: 10.1016/j.neuroscience.2011.09.045. Epub 2011 Sep 29.

Maternal glutamate intake during gestation and lactation regulates adenosine A₁ and A(2A) receptors in rat brain from mothers and neonates.

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1
Departamento de Química Inorgánica, Orgánica y Bioquímica, Facultad de Químicas, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha, Avenida Camilo José Cela, 1013071 Ciudad Real, Spain.

Abstract

Pregnant rats were treated daily with 1 g/L of L-glutamate in their drinking water during pregnancy and/or lactation. The effect on adenosine A₁ receptor (A₁R) and A(2A) receptor (A(2A)R) in brains from both mothers and 15-day-old neonates was assayed using radioligand binding and real time PCR assays. Mothers receiving L-glutamate during gestation, lactation, and throughout gestation and lactation showed a significant decrease in total A₁R number (water+water, 302±49 fmol/mg; L-glutamate+water, 109±11 fmol/mg, P<0.01; water+L-glutamate, 52±13 fmol/mg, P<0.01; L-glutamate+L-glutamate, 128±33 fmol/mg, P<0.05). No variations were detected in the Kd parameter. Concerning adenosine A(2A)R, radioligand binding assays revealed that Bmax parameter remains unaltered in maternal brain in response to glutamate exposure. However, Kd parameter was significantly decreased in all L-glutamate-treated groups (water+water, 5.3±1.3 nM; L-glutamate±water, 0.5±0.1 nM; water+L-glutamate, 0.9±0.1 nM; L-glutamate±L-glutamate, 0.7±0.1 nM, P<0.01 in all cases). In both male and female neonates, A₁R was also decreased after long-term glutamate exposure during gestation, lactation, and gestation plus lactation (male neonates: water+water, 564±68 fmol/mg; L-glutamate+water, 61±8 fmol/mg; water+L-glutamate, 95±20 fmol/mg; L-glutamate+L-glutamate, 111±15 fmol/mg; P<0.01 in all cases; female neonates: water+water, 216±35 fmol/mg; L-glutamate+water, 59±9 fmol/mg; water+L-glutamate, 139±16 fmol/mg; L-glutamate+L-glutamate, 97±14 fmol/mg; P<0.01 in all cases). No variations were found in mRNA level coding adenosine A(1)R in maternal or neonatal brain. Concerning adenosine A(2A)R, radioligand binding assays revealed that Bmax parameter was significantly increased in male and female neonates exposed to L-glutamate during lactation (male neonates: water+water, 214±23 fmol/mg; water+L-glutamate, 581±49 fmol/mg; P<0.01; female neonates: water+water, 51±10 fmol/mg; water+L-glutamate, 282±52 fmol/mg; P<0.05). No variations were found in mRNA level coding adenosine A(2A)R in maternal or neonatal brain. In summary, long-term L-glutamate treatment during gestation and lactation promotes a significant down-regulation of A₁R in whole brain from both mother and neonates and a significant up-regulation of A(2A)R in neonates exposed to L-glutamate during lactation.

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