Prenatal and Postnatal Contents of Amino Acid Neurotransmitters in Mouse Parietal Cortex

Abstract

This study documents the variation in the amino acid neurotransmitter contents during mouse parietal cortex development, from embryonic day 13 (E13) until young adulthood, between postnatal day 21 (P21) and P30. Taurine, an inhibitory neurotransmitter and neuromodulator, is the most abundant neurotransmitter in the developing neocortex, whereas, at the adult stage, glutamate is the more prominent neurotransmitter playing an excitatory role, and GABA is the major inhibitory neurotransmitter. During the proliferative stage of neurogenesis in the mouse cerebral cortex, between E13 and E17, relatively high levels of glutamate, aspartate, taurine and glycine were detected, consistent with a possible trophic influence of these neurotransmitters during cortical development prior to synaptogenesis. Between E17 and E19, a significant decline in the contents of these neurotransmitters was observed, consistent with earlier reports of cell death in the ventricular and subventricular zones during this stage of development. During the perinatal period, a progressive increment in glutamate level was seen between E21 and P5, and then the values remained constant until the second postnatal week. Glutamate also decreased by about 25% between P11 and P15, on the other hand, aspartate diminished by about 20% between P7 and P9. These results were consistent with previous reports of histogenetic cell death during the first 2 postnatal weeks in mouse neocortex. GABA increased from the embryonic period until young adulthood, in contrast, the glycine content decreased; thus, in the adult parietal cortex, the GABA content was about 2.6-fold higher than that of glycine. During the first postnatal week, the concentrations of glutamate and GABA showed significant increments between P0 and P5, while those of aspartate and glycine remained constant. During this period, amino acids are predominantly excitatory and the cerebral cortex is vulnerable to epileptiform activity; the significant increment in taurine content between P0 and P3 suggests a neuroprotective action of taurine against excitotoxicity. At P15, coinciding with the period of maximum cortical synaptogenesis, significant increments in GABA and glycine contents were observed which could be related to the maturation of inhibitory synaptic transmission. At the young adult stage, there was a rise in the levels of both excitatory neurotransmitters, glutamate and aspartate, and a significant reduction in the contents of all three inhibitory neurotransmitters, GABA, glycine and taurine.

Single-neuron identification of chemical constituents, physiological changes, and metabolism using mass spectrometry

“…In addition to the coexistence of Glu and GABA, consistent with previous studies reporting age-dependent changes in multiple neurotransmitter systems in brain tissue (36,37), we also found that the concentrations of amino acids neurotransmitters, including Glu and GABA, in single cells decrease with age. Interestingly, we observed that the correlation among single-cellular Gln, Glu, and GABA is much more significant in infants than that in children or adolescents.…”

“…( Changes in the Levels of Cytoplasmic Chemical Constituents at Different Stages of Brain Development. Previous reports suggest that the levels of amino acid neurotransmitters tend to decrease with age (36,37). Using single-cell MS, we investigated this idea at the single-neuron level.…”

The neurochemical profile quantified by in vivo 1H NMR spectroscopy

“…Like for NAAG, the highest glycine concentrations in the brain are observed at P10 and decline until adulthood (Kulak et al, 2010). In fact, the rate of glycine synthesis peaks around 10-15 days after birth (Benítez-Diaz et al, 2003;Lahoya et al, 1980) and likewise, during this period, glycine receptors undergo a major switch of the relative expression of glycinergic subunits (Lynch, 2004). It is interesting to note that the increase in levels of excitatory neurotransmitters, glutamate and aspartate (NMDA receptor agonists), is paralleled by a reduction in the concentration of its modulator NAAG as well as its co-agonist glycine.…”

Na + channel-mediated Ca 2+ entry leads to glutamate secretion in mouse neocortical preplate

“…To assess the physiological relevance of the pathway described above, we look to the possibility of physiological activators of the Na ϩ channel in PP cells. Glycine and͞or taurine appear as potential candidates because they are abundantly present in embryonic neocortex (7,25), together with their target receptor, the GlyR (25). Activation of GlyRs during embryonic stages is excitatory, leading to membrane depolarization (25), which can, in turn, activate Na ϩ channels.…”

“…GABA and glutamate are both present in the neocortical wall and can regulate neuronal progenitor proliferation (4,5) and neuronal migration (6). Taurine and glycine are also present and have been reported to be the most abundant neurotransmitters at E13 in mouse neocortex (7). Little is known about the channels and pathways that are involved in this early activity, and particularly little is known about how these neurotransmitters are secreted before the appearance of voltage-dependent Ca 2ϩ channels (8,9).…”