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  • bicuculline Although both receptors mGluR and mGluR are

    2022-01-27

    Although both receptors, mGluR1 and mGluR5, are present in cortical and hippocampal areas from 1 to 2 weeks old neonates (López-Bendito et al., 2002) we have found that only mGluR1 was regulated after maternal l-Glu consumption. A possible explanation could be based on the different ontogenetic profiles. Thus, the expression of mGlu1 receptors increases with age whereas expression of mGlu5 receptors progressively declines during postnatal development in many bicuculline regions (López-Bendito et al., 2002). It is also interesting to note that mGluR1/5 density and group I mGluR functionality were unaffected in brain from female neonates. This result agrees with a previous work where maternal l-Glu consumption exerted more patent effects in male than in female neonates (Hermanussen et al., 2006). A possible explanation could rely on sexual hormone actions. Thus, it has been described that estrogen decrease blood l-Glu level (Zlotnik et al., 2012). In that sense, we have shown that the plasma glutamate level was significantly lower in female neonates exposed to maternal l-Glu. Furthermore, a neuroprotective role of estrogen in CNS has been suggested by Pawlak et al. (2005) who showed that estrogen increased the glutamate uptake capacity of astrocytes by increasing the expression of glutamate transporter GLT-1 and GLAST. The possibility that estrogen can prevent glutamate-mediated excitotoxicity was suggested. Supporting the idea that estrogen could be involved in the differences observed in mGluR density and functionality between male and female neonates, several works have shown the presence of functional estrogen receptors in neonatal female rats (Patchev et al., 2004). We unknown the consequences of mGluR1 down-regulation and group I mGluR desensitization observed in the present work. However, it could be very relevant since a previous work carried out in organotypic hippocampal slice cultures from 7 days old Wistar rat pups have suggested that mGluR1 activation is required to facilitate neurogenesis (Baskys et al., 2005). Thus, when organotypic slice cultures, grown for 2 weeks in vitro, were treated with 10 μM LY367385, a selective antagonist of mGluR1, for 2 h, a significant decrease in TOAD-64 immunoreactive cells was observed in cultures. Taking into account that TOAD-64 (tuned-on after division, 64 kDa) is a marker of newly generated neuronal cells, authors suggested that mGluR1 activation may be important in facilitating hippocampal neurogenesis. In that sense, the results obtained in the present work could imply that the neurogenesis process in male neonates exposed to maternal l-Glutamate consumption during lactation could be negatively affected. In addition to neurogenesis, mGluR1 play an important role in other processes. Thus, several evidences obtained using selective antagonist and mutant mice lacking mGluR1 have suggested that mGluR1 play an important role in both synaptic plasticity and in learning and memory processes (Aiba et al., 1994; Conquet et al., 1994; Naie and Manahan-Vaughan, 2005; Steckler et al., 2005). It is tempted, therefore, to speculate that cognitive processes in neonatal period and, even, in adulthood could be altered by maternal l-Glutamate consumption during lactation. Nevertheless, further investigations are necessary in order to verify this hypothesis. In summary, the aim of the present work was to determine whether glutamate, widely consumed in the daily dietary, affected one important transduction pathway in developing brains using Wistar rats as animal model which consumed l-glutamate in the drinking water during lactation period. Results show that transduction pathways mediated by group I mGlu receptors are affected in male brain being the corresponding in female brain preserved, suggesting a gender-specific modulation of these GPCRs. Whether breastfeeding women should be careful with excessive glutamate in the daily dietary or whether this glutamate consumed during lactation could have important consequences in the developing human brain require further studies.