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Postnatal administration of allopregnanolone modifies glutamate release but not BDNF content in striatum samples of rats prenatally exposed to ethanol.

Yunes R, Estrella CR, García S, Lara HE, Cabrera R - Biomed Res Int (2015)

Bottom Line: Interestingly, this effect was reverted by allopregnanolone.However, both ethanol alone and ethanol plus allopregnanolone treated animals did not show any change regarding control values.Furthermore, the reciprocal interactions found between GABAergic neurosteroids and BDNF could underlie mechanisms operating during the neuronal plasticity of fetal development.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Investigaciones Biomédicas (INBIOMED-IMBECU-CONICET), Facultad de Ciencias de la Salud, Universidad de Mendoza, Paseo Dr. Emilio Descotte 720, 5500 Mendoza, Argentina ; Área de Farmacología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Avenidad del Libertador 80, 5500 Mendoza, Argentina.

ABSTRACT
Ethanol consumption during pregnancy may induce profound changes in fetal CNS development. We postulate that some of the effects of ethanol on striatal glutamatergic transmission and neurotrophin expression could be modulated by allopregnanolone, a neurosteroid modulator of GABAA receptor activity. We describe the acute pharmacological effect of allopregnanolone (65 μg/kg, s.c.) administered to juvenile male rats (day 21 of age) on the corticostriatal glutamatergic pathway, in both control and prenatally ethanol-exposed rats (two ip injections of 2.9 g/kg in 24% v/v saline solution on gestational day 8). Prenatal ethanol administration decreased the K(+)-induced release of glutamate regarding the control group. Interestingly, this effect was reverted by allopregnanolone. Regarding BDNF, allopregnanolone decreases the content of this neurotrophic factor in the striatum of control groups. However, both ethanol alone and ethanol plus allopregnanolone treated animals did not show any change regarding control values. We suggest that prenatal ethanol exposure may produce an alteration of GABAA receptors which blocks the GABA agonist-like effect of allopregnanolone on rapid glutamate release, thus disturbing normal neural transmission. Furthermore, the reciprocal interactions found between GABAergic neurosteroids and BDNF could underlie mechanisms operating during the neuronal plasticity of fetal development.

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Related in: MedlinePlus

Panel (a): 3H-Glu uptake from rat striatal slices; Panel (b): 3H-Glu fractional release induced from rat striatal slices by 28 mM K+. Control (white bars) or prenatal ethanol-exposed (gray bars) male rats were injected with allopregnanolone (65 μg/kg) or vehicle on P21, 2.5 h before the experiment. Results are expressed as mean ± SEM (n = 6–9) (different letters indicate statistically significant differences).
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fig1: Panel (a): 3H-Glu uptake from rat striatal slices; Panel (b): 3H-Glu fractional release induced from rat striatal slices by 28 mM K+. Control (white bars) or prenatal ethanol-exposed (gray bars) male rats were injected with allopregnanolone (65 μg/kg) or vehicle on P21, 2.5 h before the experiment. Results are expressed as mean ± SEM (n = 6–9) (different letters indicate statistically significant differences).

Mentions: As an index of the activity of the glutamatergic neurons, induced by prenatal ethanol treatment and acute postnatal pharmacological treatment with allopregnanolone we measured changes in the uptake and release of glutamic acid from corpus striatum slices obtained from the animals that received or did not receive prenatal ethanol. No change in striatal 3H-Glu uptake was observed after prenatal exposure to ethanol (Figure 1(a)). On the other hand, both control and prenatal ethanol-exposed rats injected s.c. with 5 allopregnanolone decreased the 3H-Glu uptake (P < 0.05) in relation to the vehicle injection alone (Figure 1(a)). A clear decrease of 3H-Glu release was found in response to the depolarizing stimulus in the prenatal ethanol-exposed rats (Figure 1(b)). The injection of allopregnanolone significantly decreased the stimulus-evoked release of 3H-Glu in control rats (P < 0.01). Interestingly, the opposite trend is observed in the prenatal ethanol-exposed rats injected with allopregnanolone (Figure 1(b)).


Postnatal administration of allopregnanolone modifies glutamate release but not BDNF content in striatum samples of rats prenatally exposed to ethanol.

Yunes R, Estrella CR, García S, Lara HE, Cabrera R - Biomed Res Int (2015)

Panel (a): 3H-Glu uptake from rat striatal slices; Panel (b): 3H-Glu fractional release induced from rat striatal slices by 28 mM K+. Control (white bars) or prenatal ethanol-exposed (gray bars) male rats were injected with allopregnanolone (65 μg/kg) or vehicle on P21, 2.5 h before the experiment. Results are expressed as mean ± SEM (n = 6–9) (different letters indicate statistically significant differences).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4352491&req=5

fig1: Panel (a): 3H-Glu uptake from rat striatal slices; Panel (b): 3H-Glu fractional release induced from rat striatal slices by 28 mM K+. Control (white bars) or prenatal ethanol-exposed (gray bars) male rats were injected with allopregnanolone (65 μg/kg) or vehicle on P21, 2.5 h before the experiment. Results are expressed as mean ± SEM (n = 6–9) (different letters indicate statistically significant differences).
Mentions: As an index of the activity of the glutamatergic neurons, induced by prenatal ethanol treatment and acute postnatal pharmacological treatment with allopregnanolone we measured changes in the uptake and release of glutamic acid from corpus striatum slices obtained from the animals that received or did not receive prenatal ethanol. No change in striatal 3H-Glu uptake was observed after prenatal exposure to ethanol (Figure 1(a)). On the other hand, both control and prenatal ethanol-exposed rats injected s.c. with 5 allopregnanolone decreased the 3H-Glu uptake (P < 0.05) in relation to the vehicle injection alone (Figure 1(a)). A clear decrease of 3H-Glu release was found in response to the depolarizing stimulus in the prenatal ethanol-exposed rats (Figure 1(b)). The injection of allopregnanolone significantly decreased the stimulus-evoked release of 3H-Glu in control rats (P < 0.01). Interestingly, the opposite trend is observed in the prenatal ethanol-exposed rats injected with allopregnanolone (Figure 1(b)).

Bottom Line: Interestingly, this effect was reverted by allopregnanolone.However, both ethanol alone and ethanol plus allopregnanolone treated animals did not show any change regarding control values.Furthermore, the reciprocal interactions found between GABAergic neurosteroids and BDNF could underlie mechanisms operating during the neuronal plasticity of fetal development.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Investigaciones Biomédicas (INBIOMED-IMBECU-CONICET), Facultad de Ciencias de la Salud, Universidad de Mendoza, Paseo Dr. Emilio Descotte 720, 5500 Mendoza, Argentina ; Área de Farmacología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Avenidad del Libertador 80, 5500 Mendoza, Argentina.

ABSTRACT
Ethanol consumption during pregnancy may induce profound changes in fetal CNS development. We postulate that some of the effects of ethanol on striatal glutamatergic transmission and neurotrophin expression could be modulated by allopregnanolone, a neurosteroid modulator of GABAA receptor activity. We describe the acute pharmacological effect of allopregnanolone (65 μg/kg, s.c.) administered to juvenile male rats (day 21 of age) on the corticostriatal glutamatergic pathway, in both control and prenatally ethanol-exposed rats (two ip injections of 2.9 g/kg in 24% v/v saline solution on gestational day 8). Prenatal ethanol administration decreased the K(+)-induced release of glutamate regarding the control group. Interestingly, this effect was reverted by allopregnanolone. Regarding BDNF, allopregnanolone decreases the content of this neurotrophic factor in the striatum of control groups. However, both ethanol alone and ethanol plus allopregnanolone treated animals did not show any change regarding control values. We suggest that prenatal ethanol exposure may produce an alteration of GABAA receptors which blocks the GABA agonist-like effect of allopregnanolone on rapid glutamate release, thus disturbing normal neural transmission. Furthermore, the reciprocal interactions found between GABAergic neurosteroids and BDNF could underlie mechanisms operating during the neuronal plasticity of fetal development.

Show MeSH
Related in: MedlinePlus