Contents of several amino acids in the cerebellum, brain stem and cerebrum of the 'staggerer', 'weaver' and 'nervous' neurologically mutant mice.

The content of glutamate, GABA, aspartate, glycine and alanine was determined in the cerebellum, brain stem and cerebrum of three different mutant mice which have been named ‘staggerer’, ‘weaver’ and ‘nervous’ on the basis of neurological symptoms. In the ‘staggerer’ and ‘weaver’ mutants there is an almost complete absence of granule cells in the cerebellar cortex while in the ‘nervous’ mutant there is a loss of Purkinje cells (and to a lesser extent a loss of granule cells) in the cerebellar cortex. In the cerebellum of the ‘weaver’ mutant, the content of glutamate was signficantly lower (P < 0.025) than control values (8.77 ± 0.76 vs 12.0 ± 1.3 μmol/g tissue wet wt) and the contents of GABA and glycine were significantly greater than normal levels. In the cerebellum of the ‘staggerer’ mutant, the content of glutamate was significantly lower (6.62 ± 0.70 μmol/g) and the contents of glycine and alanine significantly higher than control values. In the cerebrum and brain stem regions of the staggerer mutant, weaver mutant and the normals the contents of the five amino acids were the same. The contents of glycine and alanine in the cerebellum, GARA and glycine in the brain stem and GABA and alanine in the cerebrum of the nervous mutants were higher than control values. The data are discussed in terms of a possible role for glutamate functioning as an excitatory transmitter when released from the cerebellar granule cells.     

Effects of 3-acetylpyridine on the levels of several amino acids in different CNS regions of the rat

The effects of one intraperitoneal injection of 60–65 mg/kg of 3-acetylpyridine (3-AP) on the levels of aspartate, glutamate, GABA, taurine, glycine, and alanine in the cerebellum, medulla, telencephalon, and diencephalon-mesencephalon of the rat were studied at various times (4–28 days) after injection. In the first 4–7 days, the levels of glutamate, GABA, glycine, and alanine in the cerebellum were 10–30% higher in the 3-AP-treated rats than in the control animals. By day 14, the levels of these four amino acids were normal (in the case of glutamate and glycine) or below normal (for GABA and alanine). By day 21, the values for GABA and alanine returned to normal. In the first 7 days, the level of aspartate in the cerebellum was the same in both the 3-AP- and saline-injected groups. From days 14 to 28, the level of aspartate in the cerebellum was 10–20% lower in the 3-AP-injected group than in the saline-treated animals. The level of taurine in the cerebellum was 15–30% lower in the 3-AP group than in the control group from days 7 to 28. The pattern of changes observed in the medulla in the first 7 days was similar to that found in the cerebellum for this period. However, unlike the data for the cerebellum, the level of aspartate in the medulla was unchanged by the 3-AP injection from day 14 to day 28, and the level of glutamate in the medulla remained higher (10–15%) from days 14 to 28 in the 3-AP-injected animals with respect to control values. The levels of taurine in the medulla were lower (10–15%) from day 7 to day 28 in the 3-AP injected group with respect to control values. The injection of 3-AP did not alter the levels of aspartate, glutamate, GABA, taurine, glycine, or alanine in the telencephalon on days 7, 14, 21, or 28 and in the diencephalon-mesencephalon on day 21 with respect to control levels.     

Turnover rates of amino acid neurotransmitters in regions of rat cerebellum

The turnover rates of aspartate, gamma-aminobutyric acid (GABA), glutamate, glutamine, alanine, serine, and glycine were measured in five regions of rat cerebellum. Turnover rates of the putative neurotransmitters (aspartate, glutamate, and GABA) were 2-20-fold higher than those of alanine and serine, and generally consistent with the proposed neurotransmitter functions for these amino acids. However, glutamate turnover was high and similar in magnitude in the deep nuclei and granule layer, suggesting possible release, not only from parallel fibers, but from mossy fibers as well. The differential distribution of turnover rates for GABA supports its neuronal release by Purkinje, stellate, basket, and Golgi cells, whereas aspartate may be released by both climbing and mossy fibers. The distribution of glycine turnover rates is consistent with release from Golgi cells, whereas alanine may be released from granule cell parallel fibers. Turnover rates measured in two other motor areas, the striatum and motor cortex, indicated that utilization of these amino acid neurotransmitters is differentially distributed in brain motor regions. The data indicate that turnover rate measurements may be useful in identifying neurotransmitter function where content measurements alone are insufficient.     

Loss of Sulfoglucuronyl and Other Neolactoglycolipids in Purkinje Cell Abnormality Murine Mutants

A significant reduction in the content of two members of the sulfoglucuronyl-neolacto series of glycolipids (SGGLs), 3-sulfoglucuronyl-lacto-N-neotetraosylceramide (SGGL-1) and 3-sulfoglucuronyl lacto-N-norhexaosylceramide (SGGL-2), in the cerebellum of the Purkinje cell abnormality mutants, Purkinje cell degeneration (pcd/pcd), lurcher (Lc/+), and staggerer (sg/sg), was also confirmed in the mildly affected nervous (nr/nr) mutant. The expression of SGGLs was studied during development of the pcd/pcd mutant cerebellum, and it was shown that the rate of decline in the level of SGGLs practically coincided with the loss of Purkinje cell perikarya. This indicated that SGGLs are primarily localized in Purkinje cells and that initially, at least, there is no genetic defect in the biosynthesis of SGGLs in the mutant. The precursors of SGGLs, viz., lacto-N-neotetraosylceramide (paragloboside) and lacto-N-norhexaosylceramide, as well as other glycolipids derived from these precursors, such as X-determinant fucoglycolipids and disialosyllacto-N-neotetraosylceramide, were also present in normal cerebellum. Levels of paragloboside and its other derivatives, similar to SGGLs, were also significantly reduced in the Purkinje cell abnormality mutants pcd/pcd, sg/sg, Lc/+, and nr/nr but were normal in other cerebellar mutants, such as quaking (qk/qk), weaver (wv/wv), and reeler (rl/rl), where Purkinje cells are not involved. Thus, the entire paragloboside family of glycolipids is primarily associated with Purkinje cells in the cerebellum. Although levels of monoclonal antibody HNK-1-reactive glycolipids were reduced in the Purkinje cell abnormality mutants, HNK-1-reactive glycoproteins were not affected in these mutants.     

Levels of several amino acids in the cerebellar peduncles and four medullary nuclei of control and 3-acetylpyridine-treated rats

The levels of aspartate, glutamate, GABA, taurine, glycine, and alanine were determined in the inferior (ICP), middle (MCP) and superior (SCP) cerebellar peduncles, and in the inferior olive (ION), lateral reticular (LRN), lateral vestibular (LVN) and descending trigeminal (DTN) nuclei of control rats and of rats given a single intraperitoneal injection of 65 mg/kg of 3-acetylpyridine (3-AP). The content of glutamate in the MCP and SCP was 30% higher than that found for the ICP. The content of GABA was 4 to 6-fold greater in the SCP than in either the ICP or MCP. The level of taurine in the SCP was 25% lower than the value in the MCP but was not significantly lower than the value for the ICP. The levels of aspartate, glycine, and alanine were evenly distributed among the three peduncles. The contents of aspartate, glutamate, taurine, and alanine were evenly distributed among the four medullary nuclei. The level of glycine was significantly greater in the DTN than in either the LRN or LVN. The content of GABA in the ION and LVN was significantly greater than the value found for the LRN. Injection of 3-AP caused a decrease in the level of taurine of 10% in the ION and LRN, 15% in the LVN, and 25% in the DTN. No other statistically significant differences were found in the levels of the amino acids in the peduncles or medullary nuclei following 3-AP treatment. The present data do not support the idea that asparate and/or taurine are present in relatively high concentrations in the cerebellar climbing fibers.     

Effect of aging on 24-hour changes in dopamine and serotonin turnover and amino acid and somatostatin contents of rat corpus striatum

This study examined the 24-hour changes in a number of transmitters in the corpus striatum of young and middle-aged male Wistar rats. The contents of excitatory amino acids (glutamate, aspartate) and inhibitory amino acids (gamma-aminobutyric acid, GABA; taurine, glycine) and of somatostatin were measured in 2-month- and 18- to 20-month-old rats killed at six different time points along the 24-hour cycle. The striatal serotonin and dopamine turnover was also measured. Both young and middle-aged rats showed significant 24-hour variations in striatal glutamate and aspartate contents; only in young rats these variations fitted a cosine function, with acrophase during the first part of rest span. Mesor values of striatal excitatory amino acid contents were lowest in middle-aged rats. Significant 24-hour variations in striatal contents of GABA, taurine, and glycine occurred in young rats, while only striatal GABA exhibited 24-hour changes in middle- aged rats (acrophases during the first part of rest span). For every inhibitory transmitter, the mesor values in middle-aged rats were significantly lower than in young rats. The 24-hour variation of the striatal somatostatin content showed acrophase during the first part of rest span, mesor values and amplitude being lowest in middle-aged rats. Aging rats exhibited significantly higher mesor values of striatal serotonin turnover (34% increase) and lower mesor values of dopamine turnover (69% decrease) than their younger counterparts. Some of the circadian modifications of motor function seen in aging rats could be related to the striatal transmitter changes reported herein.     

Effects of selective doses of x-irradiation on the levels of several amino acids in the cerebellum of the rat

The cerebella of rats were exposed to selective doses of low levels of x-irradiation beginning on day 4, 8, or 12 following birth. The doses of x-irradiation given on days 12, 13, and 15 (12–15X group) resulted in a 24% reduction in the wet weight of the cerebella; the doses given on days 8, 9, 11, 13, and 15 (8–15X group) resulted in a 57% weight reduction; the doses given on days 4, 5, 7, 9, 11, 13, and 15 (4–15X group) resulted in a 67% weight reduction. The schedule of x-irradiation begun on day 12, which prevented the acquisition of the late-forming granule cells, reduced the levels (nmole/mg dry tissue weight) of alanine (22%) and glutamate (10%), and increased the levels of glycine (15%), GABA (13%), and taurine (71%), with respect to control values. The schedule begun on day 8, which prevented the acquisition of stellate and granule cells, reduced the levels of alanine (15%), glutamate (12%), and taurine (21%), and increased the levels of glycine (102%) and GABA (56%). The schedule begun on day 4, which prevented the acquisition of basket, stellate, and granule cells, reduced the level of glutamate (15%) and increased the levels of glycine (186%) and GABA (78%). The levels of alanine and taurine in the cerebella of the 4–15X group were the same as control values. The level of aspartate in the cerebella of the 3 groups of x-irradiated animals was not significantly different from control values. The consistent reduction in the level of glutamate as a function of the number of doses of x-irradiation is suggestive that glutamate may have a higher level in the granule cells than in other cells in the cerebellum, and that the higher level may be a reflection of a possible excitatory transmitter role for glutamate. In addition, the data are interpreted in terms of taurine being associated with the stellate cells and possibly serving as a transmitter for these inhibitory interneurons.     

Regional excitatory and inhibitory amino acid levels in epileptic El mouse brain

Inbred mutant El mice are highly susceptible to convulsive seizures upon tossing stimulation. The levels of excitatory (e.g. glutamate and aspartate) and inhibitory amino acids [e.g. -aminobutyrate (GABA)] were examined in discrete regions of stimulated El mice [El(+)] non-stimulated El mice [El(-)] and ddY mice, which do not have convulsive disposition. In comparison with ddY, a general increased levels of aspartate, glutamate, glutamine, and taurine were detected in brain regions of El(-). The levels of GABA and glycine were almost the same in ddY and El(-). Compared to El(+), the levels of aspartate, glutamate, glutamine, and GABA in El(-) were either the same or higher. In the case of taurine and glycine, the levels in El(-) were either the same or lower than El(+). Alanine is special in that El(-) have a higher level than El(+) in hippocampus but lower in cerebellum. Furthermore, while marked changes were registered in several brain regions, none of the amino acids investigated showed any significant differences in the hypothalamus of three different groups of mice.     

Release of Endogenous and Accumulated Exogenous Amino Acids from Slices of Normal and Climbing Fibre-Deprived Rat Cerebellar Slices

Efflux of various amino acids from slices of rat cerebellar hemispheres was determined under resting or depolarizing conditions. It was increased under high K+(50 mM) as compared to low K+ (5 mM) conditions by 1258 pmol/mg protein for aspartate, 478 for gamma-aminobutyric acid (GABA), 44,693 for glutamate, and 615 for glycine. These were significantly higher than the corresponding values obtained under low-Ca2+ (0.1 mM), high-Mg2+ (12 mM) conditions, whereas for 11 other amino acids the K+-induced efflux was similar under normal and low-Ca2+ concentrations. The K+-induced efflux of exogenously accumulated L-[3H]aspartate, D-[3H]aspartate, and L-[3H]glutamate was higher by factors of 2, 5.8, and 6.3, respectively, under normal Ca2+ conditions, as compared with low-Ca2+, high-Mg2+ conditions. After climbing fibre degeneration induced by destruction of the inferior olive with 3-acetylpyridine, release of endogenous aspartate and exogenous L-[3H]glutamate and D-[3H]aspartate was significantly reduced, by 26%, 38%, and 27%, respectively. These results support the hypothesis that climbing fibres may use aspartate or a related compound as a neurotransmitter. In rat cerebellar tissue, L-[3H]glutamate and L-[3H]aspartate differ in several aspects: (1) L-[3H]glutamate uptake was 4 times higher than that of L-[3H]aspartate; (2) fractional rate constant of K+- evoked release of L-[3H]aspartate was 7% X 2.5 min-1, and of L-[3H]glutamate 36% X 2.5 min-1; and (3) specific activity of L-[3H]glutamate in the eluate collected during K+ stimulation was 3.5 times the value in the tissue, whereas for L-[3H]aspartate, specific activities in the eluate and tissue were similar.     

Expression of the yes proto-oncogene in cerebellar Purkinje cells.

To identify the kinds of cells in the brain that express the yes proto-oncogene, we examined chicken brains by using immunofluorescent staining and in situ hybridization. Both approaches showed that the highest level of the yes gene product was in cerebellar Purkinje cells. In addition, we analyzed Purkinje cell degeneration (pcd) mutant mice. The level of yes mRNA in cerebella of pcd mutants was four times lower than that found in cerebella of normal littermates. Our studies point to Purkinje cells as an attractive model for functional studies of the yes protein.     

Local sensitivity to excitatory and inhibitory amino acids in spinal interneurons of the lamprey

Sensitivity to glutamate, aspartate, glycine and GABA was examined in giant interneurons of the lamprey spinal cord.1. The membrane potentials evoked by iontophoretic application decayed with varied time constants specific to amino acids: 2.5 sec for glutamate, 6.3 sec for glycine and 10.3 sec for GABA. li|2. Bath-applied amino acids reduced the input resistance by varying degrees; when glutamate effect was taken as 1, relative effects of aspartate, glycine and GABA were 0.28, 40.5 and 12.3, respectively.3. Glutamate sensitivity was fairly uniform in both the soma and the dendrites. Glycine sensitivity, as well as GABA, was high in the soma and declined steeply along the dendrites by iontophoresis.     

Amplification by glycine of the effect of the GABA transport inhibitor THPO on synaptosomal GABA level

Mice were injected intramuscularly (2 mmol/kg) with the glia-selective GABA uptake inhibitor 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol (THPO) 60 min prior to sacrifice, or with glycine (10 mmol/kg) 45 min before death, or with a combination of both. After decapitation of the animals, the brains were removed and synaptosomes prepared and analyzed for content of GABA, taurine, glutamine, serine, glutamate and aspartate. While no differences as compared with control animals were found for aspartate, serine and glutamine, synaptosomal GABA levels were increased significantly after injections with either THPO or glycine. The individual effects of THPO and glycine were found to be additive. Taurine levels were decreased to a similar extent in animals which had received either THPO alone or THPO in conjunction with glycine. Treatment with THPO and glycine in combination led to a decrease in the synaptosomal glutamate content. The findings are consistent with the previously observed synergistic anticonvulsant actions of THPO and glycine being mediated via the GABA neurotransmitter system.     

Levels and Synthesis of Glutamate and Aspartate in the Olfactory Cortex Following Bulbectomy

Guinea pigs were unilaterally bulbectomised and the contents of aspartate, glutamate and GABA measured in slices of olfactory cortex taken from the lesioned and intact hemispheres. Two days after the operation there was a fall in the aspartate and glutamate levels, which persisted for over 120 days, whereas gamma-aminobutyric acid (GABA) showed a transient fall followed by a small rise. The fall in glutamate and aspartate was much greater in small, thin slices containing a high density of nerve terminals. The synthesis of 13C aminoacids from [13C]glucose during electrical stimulation was greater in the slices taken from the normal side than in those from the operated side. The GABA synthesis, however, was four times greater on the lesioned side. This time-course for the fall in acidic amino acids correlates with the fall in electrical responses, and this lends weight to the idea that aspartate and/or glutamate mediate synaptic transmission in the area.     

Effects of X-irradiation induced loss of cerebellar granule cells on the synaptosomal levels and the high affinity uptake of amino acids.

Abstract— Crude synaptosomal (P₂) preparations were obtained from the cerebella of rats in which the granule cell population had been selectively reduced by X-irradiation treatment and from the cerebella of control animals. In the P₂ fraction from control cerebella, the level of glutamate was greater than any other of the 5 amino acids measured and was 2-fold higher than taurine, which was present at the next highest level. The content of taurine was slightly higher than that found for aspartate and was 3-fold greater than that observed for GABA. Alanine and glycine were present in the lowest amounts. The levels of glutamate and aspartate were significantly (P < 0.05) lower by 25 and 15%, respectively, in the P₂ fraction isolated from the X-irradiated cerebella in comparison to control values. The content of taurine, GABA, glycine, and alanine were not changed by the X-irradiation treatment. The uptake of 1.0 μm -l -[³H]glutamate and l -[³H]aspartate was reduced approx 20% by X-irradiation treatment, whereas the uptake of 1.0 μm -[³H]GABA and [³H]taurine was unchanged. A more detailed kinetic analysis of l -[³H]glutamate uptake revealed there was a 20% decrease in the V_max value with X-irradiation treatment and no change in the apparent K_m value. In a second study, the uptake of l -[³H]glutamate, l -[³H]aspartate and [³H]GABA was measured using P₂ fractions obtained from the cerebella of rats in which the population of granule, stellate and basket cells had been reduced by X-irradiation treatment. The uptake of 1.0μm -l -[³H]glutamate, l -[³H]aspartate and [³H]GABA was significantly (P < 0.05) reduced to 57, 68, and 59%, respectively, of control values. A more detailed kinetic analysis of [³H]GABA uptake revealed no significant change in the apparent K_m and a 35% decrease in the V_max value. The data are discussed in terms of glutamate being the excitatory neurotransmitter released from granule cells and GABA being the inhibitory neurotransmitter released from basket cells.     

Amino Acid Changes in Autopsied Brain Tissue from Cirrhotic Patients with Hepatic Encephalopathy

Brain tissue was obtained at autopsy from nine cirrhotic patients dying in hepatic coma and from an equal number of controls, free from neurological, psychiatric, or hepatic diseases, matched for age and time interval from death to freezing of dissected brain samples. Glutamine, glutamate, aspartate, and gamma-aminobutyric acid (GABA) levels were measured in homogenates of cerebral cortex (prefrontal and frontal), caudate nuclei, hypothalamus, cerebellum (cortex and vermis), and medulla oblongata as their o-phthalaldehyde derivatives by HPLC using fluorescence detection. Glutamine concentrations were found to be elevated two- to fourfold in all brain structures, the largest increases being observed in prefrontal cortex and medulla oblongata. Glutamate levels were selectively decreased in prefrontal cortex (by 20%), caudate nuclei (by 27%), and cerebellar vermis (by 17%) from cirrhotic patients. On the other hand, GABA content of autopsied brain tissue from these patients was found to be within normal limits in all brain structures. It is suggested that such region-selective reductions of glutamate may reflect loss of the amino acid from the releasable (neurotransmitter) pool. These findings may be of significance in the pathogenesis of hepatic encephalopathy resulting from chronic liver disease.     

Effect of Aging on 24-Hour Changes in Serotonin and Dopamine Turnover, and Somatostatin and Amino Acid Content, of the Rat Hypothalamus and Pituitary Gland

The effect of aging on neurotransmitter and peptide content in the hypothalamichypophysial unit has commonly been analyzed at single time points in the 24-h cycle. Since significant changes in circadian rhythmicity occur during aging, this study aimed to examine 24-h rhythmicity in hypothalamic and pituitary serotonin (5HT) and dopamine (DA) turnover and content, and somatostatin and amino acid content in 2 months-old and 18-20 months-old rats, killed at 6 different time intervals throughout the light-dark cycle. Aged rats showed suppressed or disrupted 24-h rhythms of 5HT and DA turnover and of somatostatin, glutamate, aspartate and taurine content (anterior hypothalamus), of 5HT and DA turnover and of somatostatin, glutamate, taurine and glycine content (medial hypothalamus) and of DA turnover and amino acid content (posterior hypothalamus). Twenty-four h variations in DA, somatostatin, aspartate, GABA and glycine content of the anterior hypophysis and in all parameters tested in the neurointermediate lobe became suppressed or disrupted in aged rats. Mean values generally decreased with age, except for DA content in the anterior pituitary lobe and aspartate content in the neurointermediate lobe. Conclusions: Examination of neurotransmitter and neuropeptide content at different times of the day is needed to analyze the effects of aging in the hypothalamic-hypophysial unit.     

Elevation of cerebral levels of nonessential amino acids in vivo by administration of large doses

Taurine, aspartic acid, glutamic acid, glycine, and GABA were administered either intragastrically or in liquid diets to mice and rats. This resulted in a great increase in the plasma concentration of the administered amino acid, with plasma levels remaining elevated for several days.The prolonged increase in plasma levels resulted in significant increases in brain levels. Under these experimental conditions, taurine, aspartic acid, and glutamic acid were increased 30–60%; glycine and GABA 100%. During these experiments, plasma levels of taurine, aspartate, and glutamate were below brain levels; those of glycine and GABA were above.The findings show that even slowly penetrating amino acid levels can be increased in brain after parenteral administration of large doses.     

The distribution of several amino acids in specific ganglia and nerve bundles of the lobster

Using the technique of measuring DNP-amino acid methyl esters by gas-liquid chromatography, the distribution of alanine, proline, glycine, GABA, glutamate and aspartate was determined in individual ganglia and the associated nerve bundles between these ganglia after isolation from the nervous system of the lobster, Homarus americanus. The brain or supraesophageal ganglion (27.2 mg) and the next 5 thoracic ganglia (varying from 24 to 10 mg in a rostral–caudal direction) as well as the nerve bundles connecting these ganglia were used. GABA and aspartate values varied the most among the individual ganglia; highest values were found in the second and third thoracic ganglia. The levels of alanine, proline, glycine and glutamate varied very little from ganglion to ganglion; however, the values for these amino acids did exhibit some variability among the individual connectives. The highest value for each was in the nerve bundle between the first and second thoracic ganglion. Glycine was present at the highest level of any of the amino acids whereas GABA was at the lowest level in the individual structures assayed.     

In Vitro Release of Endogenous Amino Acids from Granule Cell-, Stellate Cell-, and Climbing Fiber-Deficient Cerebella

Abstract: The K⁺-stimulated, Ca²⁺-dependent release of glutamate, aspartate, -γ-aminobutyric acid (GABA), alanine, taurine, and glycine was measured in slices of cerebella obtained from control, and granule cell-, granule cell plus stellate cell-, or climbing fiber-deficient cerebella of the rat. The 55 mm -K⁺-stimulated release of glutamate and GABA was 10-fold greater in the presence of Ca²⁺ than in its absence. The stimulated release of aspartate was 4-fold higher when Ca²⁺ was present in the bathing media, while the value for alanine was twice as high as the amount obtained in the absence of Ca²⁺. There was no stimulated release of either taurine or glycine from the cerebellar slices. Increasing the Mg²⁺ concentration to 16 HIM inhibited the K⁺-stimulated, Ca²⁺-dependent release of glutamate, GABA, aspartate, and alanine 85% or more. The K⁺-stimulated, Ca²⁺ dependent release of glutamate, aspartate, and alanine from x-irradiated cerebella deficient in granule cells was reduced to 50–57% of control value. Additional x-irradiation treatment, which further reduced the cerebellar granule cell population and also prevented the acquisition of stellate cells, decreased the release of glutamate by 77%, aspartate by 66%, alanine by 91%, and, in addition, decreased the release of GABA by 55%. The K⁺-stimulated, Ca²⁺-dependent release of glutamate, aspartate, GABA, and alanine was not changed in climbing fiber-deficient cerebella obtained from 3-acetylpyridine-treated rats. The data support a transmitter role for GABA and glutamate in the cerebellum, but do not support a similar function for either taurine or glycine. The data also suggest that alanine and aspartate may be co-released along with glutamate from granule cells.     

Regional changes in amino acid levels of the neonate rat brain during anoxia and recovery

The aim of this study was to compare the changes in amino acids (alanine, aspartate, GABA, glutamate, glutamine, glycine, serine taurine) that are produced in different regions of the neonate brain (telencephalon, diencephalon cerebellum, brain stem) following a survivable period of anoxia and after the re-establishment of air respiration. Anoxia provoked different responses in the different regions. The changes during the anoxic period were as follows. In the brain stem there was a decrease in aspartate, in the telencephalon there was a significant increase in GABA and alanine and a decrease in aspartate, in the diencephalon, glutamate and GABA increased, and in the cerebellum, glycine and alanine levels were enhanced. The changes during recovery were even more dissimilar. Here the greatest shifts were seen in the brain stem with increases in glutamine, GABA, aspartate, glycine, serine, alanine, and taurine. In the telencephalon glutamate fell and alanine increased, in the diencephalon GABA increased, and in the cerebellum, glutamate fell while glycine and alanine increased. In none of the major brain regions did the pattern of changes in neurotransmitters correspond to that seen in anoxic tolerant species.