Neuroexcitatory amino acids: 4-methylene glutamic acid derivatives

Summary A short synthesis of 4-methylene glutamic acid was achieved. Under thermal conditions the corresponding anhydride reacted with 2,3 dimethylbutadiene to afford the corresponding DIELS-ALDER adduct in good yield. L-4-methylene glutamic acid essentially acts on glutamate metabotropic receptors and is as potent as L-Glu in producing IPs.     

Lipophilicity of amino acids

Summary The lipophilicity (or hydrophobicity) of amino acids is an important property relevant for protein folding and therefore of great interest in protein engineering. For peptides or peptidomimetics of potential therapeutic interest, lipophilicity is related to absorption and distribution, and thus indirectly relates to their bioactivity. A rationalization of peptide lipophilicity requires basic knowledge of the lipophilicity of the constituting amino acids. In the present contribution we will review methods to measure or calculate the lipophilicities of amino acids, including unusual amino acids, and we will make a comparison between various lipophilicity scales.     

Changes in Extracellular Concentrations of Glutamate, Aspartate, Glycine, Dopamine, Serotonin, and Dopamine Metabolites After Transient Global Ischemia in the Rabbit Brain

Although considerable evidence supports a role for excitatory amino acids in the pathogenesis of ischemic neuronal injury, few in vivo studies have examined the effect of increasing durations of ischemia on the extracellular concentrations of these agents. Recently, other neurotransmitters (e.g., glycine and dopamine) have been implicated in the mechanism of ischemic neuronal injury. Accordingly, this study was undertaken to examine the patterns of changes of extracellular glutamate, aspartate, glycine concentrations in the hippocampus, and dopamine, serotonin, and dopamine metabolites in the caudate nucleus with varying durations (5, 10, or 15 minutes) of transient global cerebral ischemia as evidence to support their pathogenetic roles. Microdialysis was used to sample the brain's extracellular space before, during, and after the ischemic period. Glutamate and aspartate concentrations in the dialysate increased from baseline by 1-, 5-, and 13-fold and by 4-, 9-, and 31-fold, respectively, for the three ischemic durations. The concentrations returned to baseline rapidly after reperfusion. The peak concentrations of glutamate and aspartate were significantly higher with increasing ischemic duration. Dopamine concentrations increased by approximately 700-fold in response to all three ischemic durations and returned to baseline within 10 min of reperfusion. Glycine, in contrast, increased during ischemia by a mean of 4-fold, but remained elevated throughout the 80-min period of reperfusion. The final concentrations of glycine were significantly higher than baseline levels (p = 0.0002, Mann-Whitney test). That glutamate and aspartate concentrations in the hippocampus co-vary with the duration of global ischemia is taken as supportive evidence of their pathogenetic role in ischemic neuronal injury.(ABSTRACT TRUNCATED AT 250 WORDS)     

Free amino acids in some sponges

Most invertebrates, particularly those of marine origin, have relatively high concentrations of free amino acids which are considered an important constituent of their osmoregulatory mechanisms [1]. Very little information is available on the free amino acid distribution in Porifera [2,3]. Common amino acids in some sponges were recognised by paper chromatography by Inskip and Cassidy [4] and Ackermann et al. [5,6] included a few sponges in their survey of the occurence of nitrogen compounds in marine invertebrates. More recently Bergquist and Hartman [7] surveyed semiquantitatively the distribution of free amino acids in several sponges. In the present paper we report on the amino acid composition of 12 species of sponges belonging to the class Demospongiae as a part of a study on the metabolites of Porifera [8]. Fresh sponges were extracted with aqueous ethanol. The organic solvent was removed and the aqueous solution, after removal of the ether soluble compounds, was separated into cationic, anionic and neutral fractions by ion-exchange chromatography. The cation fraction was analysed for amino acids using an automatic amino acid analyser. The results, which are presented in Table 1, show that all species of sponges examined have a similar composition in common amino acids. Glycine almost always appears as the dominant protein amino acid, followed by high concentrations of alanine and glutamic acid, whereas relatively lower concentrations of basic amino acids are present. In Axinella cannabina, Chondrosia reniformis, Chondrilla nucula, Cliona viridis and Hymeniacidon sanguinea, glycine represents more than 77% of the total amino acids. The high percentage of free glycine (90.4%) in Chondrosia reniformis is noteworthy. The anionic and the neutral fractions were examined for sulfur-containing amino acids using PC. Taurine (Table 2) was detected in all the Porifera examined; this is in agreement with previous observations [5–7]. N-Methyltaurine was identified in some of the species examined, whereas neither N,N-dimethyltaurine nor N,N,N-trimethyltaurine were found.     

Changes with aging in the levels of amino acids in rat CNS structural elements II. Taurine and small neutral amino acids

Taurine (Tau) and the small neutral amino acids glycine (Gly), serine (Ser), threonine (Thr), and alanine (Ala) were measured in 53 brain areas of 3- and 29-month-old male Fisher 344 rats. The ratio of highest to lowest level was 34 for Tau, 9.1 for Thr, 7.6 for Gly and Ser, and 6.5 for Ala. The heterogeneity was found in numerous areas; for example, Tau levels were more than 90 nmol/mg protein in 6 areas, and less than 20 nmol/mg protein in 10 areas. Similar heterogeneity was found with the other amino acids. The relative distribution of the small neutral amino acids showed several similarities; Tau distribution was different. With age, four amino acids decreased in 10–18 areas, and increased in only 1–3, while Thr increased in more areas than it decreased. The five amino acids of this paper, and the four of the previous paper, are among the amino acids at highest level in the brain; the sequence in their levels shows considerable regional heterogeneity.     

重复经颅磁刺激对创伤性颅脑损伤患者脑脊液中兴奋性氨基酸含量的影响

目的：探讨重复经颅磁刺激（rTMS）对急性颅脑损伤患者脑脊液中兴奋性氨基酸（EAA）含量的影响。方法：30例创伤性颅脑损伤（TBI）病人按格拉斯哥昏迷评分分为轻型组（rTMS3）、中型组（rTMS2）、重型组（rTMS1）,每组10例,各组病人分别随机分为rTMS对照亚组（A组）及治疗亚组（B组）,每亚组5例。于TBI后第15天行腰椎穿刺采集脑脊液,采用高效液相色谱法测定脑脊液中谷氨酸（ASP）及门冬氨酸（GLU）含量。结果：脑脊液ASP和GLU水平随着脑损伤程度的加重而升高,各rTMS治疗组与相应各对照组的EAA相比,rTMS治疗组EAA的水平均低于相应对照组。结论：rTMS可通过降低TBI后脑脊液EAA水平发挥脑保护作用。脑脊液EAA的含量变化可作为TBI严重程度的生化指标。     

重复经颅磁刺激对创伤性颅脑损伤患者脑脊液中兴奋性氨基酸 含量的影响

目的:探讨重复经颅磁刺激(rTMS)对急性颅脑损伤患者脑脊液中兴奋性氨基酸(EAA)含量的影响。方法:30例创伤性颅脑损伤(TBI)病人按格拉斯哥昏迷评分分为轻型组(rTMS3)、中型组(rTMS2)、重型组(rTMS1),每组10例,各组病人分别随机分为rTMS对照亚组(A组)及治疗亚组(B组),每亚组5例。于TBI后第15天行腰椎穿刺采集脑脊液,采用高效液相色谱法测定脑脊液中谷氨酸(ASP)及门冬氨酸(GLU)含量。结果:脑脊液ASP和GLU水平随着脑损伤程度的加重而升高,各rTMS治疗组与相应各对照组的EAA相比,rTMS治疗组EAA的水平均低于相应对照组。结论:rTMS可通过降低TBI后脑脊液EAA水平发挥脑保护作用。脑脊液EAA的含量变化可作为TBI严重程度的生化指标。     

Changes in regional levels of putative neurotransmitter amino acids in brain under unilateral forebrain ischemia

The levels of the neurotransmitter amino acids glutamate, aspartate, and GABA were determined in different brain regions during ischemia and post-ischemic recirculation periods using the unilateral carotid artery occlusion model of stroke in gerbils. The levels of glutamate, aspartate and GABA in ischemic hemisphere were increased significantly by 10 min of ischemia and later declined with time. Reperfusion for 30 min following 10 min. of ischemia further enhanced the levels of glutamate and aspartate. Increase in GABA levels were found during early periods of reperfusion. Regional variations in the changes of amino acids' levels were noticed following ischemia. Hippocampus showed the highest increase in glutamate levels followed by striatum and cerebral cortex. Aspartate levels in striatum and hippocampus increased during 10 min ischemia (46% and 30%) and recirculation (70% and 79%), whereas in cerebral cortex the levels were doubled only during recirculation. Ischemia induced elevations of GABA levels were observed in cerebral cortex (68%) and in hippocampus (30%), and the levels were normalized during recirculation. No changes in GABA levels were found in striatum. It is suggested that the large increase in the levels of excitatory neurotransmitter amino acids in brain regions specially in hippocampus during ischemia and recirculation may be one of the causal factors for ischemic brain damage.     

Role of excitatory amino acids in the direct and indirect presynaptic regulation of dopamine release from nerve terminals of nigrostriatal dopaminergic neurons

Summary In vivo experiments carried out in halothane-anaesthetized cats implanted with push-pull cannulae demonstrated that glutamate (GLU) released from corticostriatal fibers triggers the release of dopamine (DA), even in the absence of activity in nigral DA cells. As shown in vitro, using rat striatal slices or synaptosomes or in vivo in the cat, both NMDA and AMPA receptors subtypes are involved in the GLU-induced release of DA. Beside this direct regulation, GLU also exert several indirect facilitatory and inhibitory controls on DA release, particularly through cholinergic and GABAergic striatal neurons. Indeed, as shown by numerous authors, the GLU-evoked release of DA is markedly reduced in the presence of tetrodotoxin, bicuculline or atropine or by previous kainate- or ibotenate-induced lesion of striatum. Differences in the presynaptic regulation of DA release in striosomal and matrix compartments have also been found with NMDA and acetylcholine. The effect of acetylcholine was of shorter duration in the matrix than in the striosomal-enriched areas. Two opposite indirect regulations of DA release could be demonstrated: one is facilitatory and involves nicotinic receptors, the other is inhibitory, involves muscarinic receptors and mediated, at least in the matrix by dynorphin containing neurons. The NMDA-evoked responses are of larger amplitude and more sensitive to tetrodotoxin in the matrix than in the striosomes. In conclusion, GLU released from corticostriatal fibers, is able to control the release of DA from terminals of nigrostriatal neurons through direct facilitatory mechanisms (NMDA and AMPA receptors), but also through indirect facilitatory and inhibitory local circuits involving cholinergic and GABAergic neurons.     

Fast-acting excitatory amino acids are involved in the enhancement of the aversiveness of the electrical stimulation of the inferior colliculus by systemic injections of muscimol

Gradual increases in the electrical stimulation of the inferior colliculus produces progressive aversive responses from vigilance, through freezing, until escape. These responses are probably mediated by excitatory amino acids (EAA) mechanisms as microinjection of glutamate into the inferior colliculus can trigger freezing responses while microinjections of NMDA cause a mixture of immobility and escape responses. Moreover, it has been shown that the neural substrates for defensive behavior in this structure are regulated by GABA-benzodiazepine mechanisms. Indeed, these responses are depressed by muscimol and midazolam locally injected into the inferior colliculus. In this work we were interested in knowing how GABAergic mechanisms interact with the EAA-mediated neural substrates of aversion generated at the inferior colliculus level. We found that while intraperitoneal injections of muscimol caused the expected antiaversive effects, unexpectedly systemic injections of muscimol enhanced the aversive reactions induced by electrical stimulation of the inferior colliculus of rats. Local injections into the central nucleus of the inferior colliculus of GDEE-an AMPA/kainate receptor antagonist-inhibited whereas AP7-a NMDA receptor antagonist-did not influence these responses. It is suggested that systemic injections of muscimol inhibit GABAergic inputs to the inferior colliculus. The removal of these inhibitory influences reduce the well-known tonic inhibitory control exerted by GABAergic mechanisms on the neural substrates of aversion of the inferior colliculus. Activation of these neural substrates by fast-acting AMPA/kainate receptors trigger the initial steps of the defense reaction in the central nucleus of the inferior colliculus.     

Excitatory amino acids, monoamine, and nitric oxide synthase systems in organotypic cultures: biochemical and immunohistochemical analysis

Summary. The nigrostriatal and mesolimbic systems of the rat have been re-constructed using the organotypic culture model, whereby neonatal brain tissue is grown in vitro for approximately one month. The nigrostriatal cultures consisted of tissue from the substantia nigra, dorsal striatum and frontoparietal cortex; while the mesolimbic cultures included the ventral tegmental area, ventral striatum and cingulate cortex. The cultures were grown at 35°C in normal atmosphere, using a tube-roller device placed in a cell incubator and changing the medium every 3–4 days. The in vitro development was evaluated with an inverted microscope equipped with a variable relief contrast function. Samples were taken directly from the medium in the culture tube and analysed for several amino acids with HPLC. After a month the cultures were fixed and processed for immunohistochemistry. High levels of glutamate and aspartate were observed every time the medium was changed, but the levels rapidly decreased reaching a steady state after approximately 24 h. A decrease in the levels was also observed along development, reaching stable values (∼2 μM and ∼0.12 μM for glutamate and aspartate, respectively) at approximately two weeks, but only when the cultures showed an apparently healthy development. The levels were approximately 10 times higher in deteriorating or apparently damaged cultures. Glutamine levels were in the mM range and remained stable along the entire experiment. No differences were observed among nigrostriatal and mesolimbic cultures. Immunohistochemistry confirmed the impressions obtained from microscopic and biochemical analysis along the in vitro development, revealing apparently healthy neuronal systems with characteristics similar to those observed in vivo, when tyrosine hydroxylase and nitric oxide synthase, markers for dopamine and nitric oxide containing neurons, respectively, were analysed. In the substantia nigra, nitric oxide synthase-positive networks surrounded tyrosine hydroxylase-positive neurons, while in the striatum nitric oxide synthase dendrites were surrounded by tyrosine hydroxylase-positive nerve terminals, suggesting a reciprocal interaction among dopamine and nitric oxide containing neurons. Thus, the organotypic model appears to capture many of the neurochemical and morphological features seen in vivo, providing a valuable model for studying in detail the neurocircuitries of the brain. Received August 31, 1999 Accepted September 20, 1999     

Changes with aging in the levels of amino acids in rat CNS structural elements I. Glutamate and related amino acids

Glutamate and related amino acids were determined in 53 discrete brain areas of 3-and 29-month-old male Fischer 344 rats microdissected with the punch technique. The levels of amino acids showed high regional variation-the ratio of the highest to lowest level was 9 for aspartate, 5 for glutamate, 6 for glutamine, and 21 for GABA. Several areas were found to have all four amino acids at very high or at very low level, but also some areas had some amino acids at high, others at low level. With age, in more than half of the areas, significant changes could be observed, decrease occurred 5 times more frequently than increase. Changes occurred more often in levels of aspartate and GABA than in those of glutamate or glutamine. The regional levels of glutamate and its related amino acids show severalfold variations, with the levels tending to decrease in the aged brain.     

Sugar amino acids in designing new molecules

Emulating the basic principles followed by Nature to build its vast repertoire of biomolecules, organic chemists are developing many novel multifunctional building blocks and using them to create ‘nature-like’ and yet unnatural organic molecules. Sugar amino acids constitute an important class of such polyfunctional scaffolds where the carboxyl, amino and hydroxyl termini provide an excellent opportunity to organic chemists to create structural diversities akin to Nature’s molecular arsenal. This article describes some of our works on various sugar amino acids and many other related building blocks, like furan amino acids, pyrrole amino acids etc. used in wide-ranging peptidomimetic studies. Published in 2005.Based on the invited lecture presented at the XVII International Symposium on Glycoconjugates held in January 12–16, 2003 at Bangalore, India.     

Role of excitatory amino acids in the regulation of dopamine synthesis and release in the neostriatum

Summary We have explored the role of excitatory amino acids in the increased dopamine (DA) release that occurs in the neostriatum during stress-induced behavioral activation. Studies were performed in awake, freely moving rats, usingin vivo microdialysis. Extracellular DA was used as a measure of DA release; extracellular 3,4-dihydroxyphenylalanine (DOPA) after inhibition of DOPA decarboxylase provided a measure of apparent DA synthesis. Mild stress increased the synthesis and release of DA in striatum. DA synthesis and release also were enhanced by the intra-striatal infusion of N-methyl-D-aspartate (NMDA), an agonist at NMDA receptors, and kainic acid, an agonist at the DL-a-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionate (AMPA)/kainate site. Stress-induced increase in DAsynthesis was attenuated by co-infusion of 2-amino-5-phosphonovalerate (APV) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), antagonists of NMDA and AMPA/kainate receptors, respectively. In contrast, intrastriatal APV, CNQX, or kynurenic acid (a non-selective ionotropic glutamate receptor antagonist) did not block the stress-induced increase in DArelease. Stress-induced increase in DA release was, however, blocked by administration of tetrodotoxin along the nigrostriatal DA projection. It also was attenuated when APV was infused into substantia nigra. Thus, glutamate may act via ionotropic receptors within striatum to regulate DA synthesis, whereas glutamate may influence DA release via an action on receptors in substantia nigra. However, our method for monitoring DA synthesis lowers extracellular DA and this may permit the appearance of an intra-striatal glutamatergic influence by reducing a local inhibitory influence of DA. If so, under conditions of low extracellular DA glutamate may influence DA release, as well as DA synthesis, by an intrastriatal action. Such conditions might occur during prolonged severe stress and/or DA neuron degeneration. These results may have implications for the impact of glutamate antagonists on the ability of patients with Parkinson's disease to tolerate stress.     

The amnesic shellfish poison domoic acid enhances neurotoxicity by excitatory amino acids in cultured neurons

Summary A recent episode of human intoxication by cultured mussels containing a rare excitatory amino acid named domoic acid, received particular attention for its neurological implications. The intoxication produced neurological problems, such as headache, confusion, and loss of memory, particularly severe at times. Neuronal damage was found in the hippocampus and amygdala of four patients. We now report that in neuronal cultures the neurotoxicity of a domoic acid-containing mussel extract is the result of domoic acid potentiation of the excitotoxic effect of glutamic acid and aspartic acid present in high amounts in mussel tissue. Moreover, we show that subtoxic concentrations of domoic acid are sufficient to potentiate glutamic acid and aspartic acid neurotoxicity. We present evidence suggesting that the neurotoxic synergism may be due to a reduction of Mg^{+ +} block at the NMDA receptor-associated channel, following activation of NON-NMDA receptors by domoic acid.     

Effects of excitatory amino acids on inositol phosphate accumulation in slices of the cerebral cortex of young and aged rats

The effects of glutamate, NMDA and quisqualate on carbachol-and norepinephrine-elicited formation of inositol phosphate (IP) were evaluated in slices prepared from the cerebral cortex of 3-and 24-month Sprague-Dawley rats. Glutamate, NMDA, and quisqualate antagonized the IP response to carbachol in a concentration-dependent fashion. This antagonism was more pronounced in aged than in young rats, both for glutamate (IC5O 0.114 and 0.210 mM) and NMDA (IC5O 0.0029 and 0.127 mM), but not for quisqualate. Glutamate (but not NMDA) also antagonized in a concentration-dependent fashion the IP response to norepinephrine, IC50s were 0.061 and 0.126 mM for aged and young rats, respectively; quisqualate had an inhibitory effect only at 1 mM concentration in the two age-groups, while in aged rats some stimulatory effect was present at 0.1 mM concentration. Glutamate, NMDA and quisqualate (1 mM) did not affect basal IP accumulation in either young or aged rats; quisqualate, however, at 0.1 mM concentration had some stimulatory effect, more pronounced in aged rats. This effect was probably responsible for the biphasic effect of quisqualate in this age-group. The most important finding consists of the demonstration of an age-related increase in the inhibitory effects of NMDA on carbachol-induced IP accumulation. This implies an altered modulation of cholinergic post-receptor mechanisms by glutamatergic mechanisms.     

Enzymes with noncanonical amino acids

Enzyme design and engineering strategies rely almost exclusively on nature's alphabet of twenty canonical amino acids. Recent years have seen the emergence of powerful genetic code expansion methods that allow hundreds of structurally diverse amino acids to be installed into proteins in a site-selective manner. Here, we will highlight how the availability of an expanded alphabet of amino acids has opened new avenues in enzyme engineering research. Genetically encoded noncanonical amino acids have provided new tools to probe complex enzyme mechanisms, improve biocatalyst activity and stability, and most ambitiously to design enzymes with new catalytic mechanisms that would be difficult to access within the constraints of the genetic code. We anticipate that the studies highlighted in this article, coupled with the continuing advancements in genetic code expansion technology, will promote the widespread use of noncanonical amino acids in biocatalysis research in the coming years.     

Effect of Impact Trauma on Neurotransmitter and Nonneurotransmitter Amino Acids in Rat Spinal Cord

N-Methyl-D-aspartate (NMDA) administration exacerbates neurological dysfunction after traumatic spinal cord injury in rats, whereas NMDA antagonists improve outcome in this model. These observations suggest that release of excitatory amino acids contributes to secondary tissue damage after traumatic spinal cord injury. To further examine this hypothesis, concentrations of free amino acids were measured in spinal cord samples from anesthetized rats subjected to various degrees of impact trauma to the T9 spinal segment. Levels of excitatory and inhibitory neurotransmitter amino acids [gamma-aminobutyric acid (GABA), glutamate, aspartate, glycine, taurine] and levels of nonneurotransmitter amino acids (asparagine, glutamine, alanine, threonine, serine) were determined at 5 min, 4 h, and 24 h posttrauma. Uninjured surgical (laminectomy) control animals showed modest but significant declines in aspartate and glutamate levels, but not in other amino acids, at all time points. In injured animals, the excitatory amino acids glutamate and aspartate were significantly decreased by 5 min posttrauma, and remained depressed at 4 h and 24 h as compared with corresponding laminectomy controls. In contrast, the inhibitory amino acids, glycine, GABA, and taurine, were decreased at 5 min postinjury, had partially recovered at 4 h, and were almost fully recovered at 24 h. The nonneurotransmitter amino acids were unchanged at 5 min posttrauma and significantly increased at 4 h, with partial recovery at 24 h. At 4 h postinjury, severe trauma caused significantly greater decreases in aspartate and glutamate than did either mild or moderate injury. These findings are consistent with the postulated role of excitatory amino acids in CNS trauma.     

Direct and indirect presynaptic control of dopamine release by excitatory amino acids

Summary Dopamine (DA) release from nerve terminals of the nigrostriatal DA neurons not only depends on the activity of nigral DA cells but also on presynaptic regulation. Glutamatergie neurons of cortical origin play a prominent role in these presynaptic regulations. The direct glutamatergic presynaptic control of DA release is mediated by N-methyl-D-aspartate (NMDA) and-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionate (AMPA) receptors, located on DA nerve terminals. In addition, by acting on striatal target cells, these glutamatergic neurons contribute also to indirect regulations of DA release involving several transmitters such as GABA, acetylcholine and neuropeptides. Diffusible messengers such as nitric oxide (NO) or arachidonic acid (AA) which are particularly formed under the stimulation of NMDA receptors may also participate to the regulation of DA release. In the present study, it will be shown that the co-application of NMDA and carbachol synergistically increases the release of [³H]-DA and that this effect is reduced by mepacrine or 4-bromophenacylbromide (10⁷M), two inhibitors of PLA2. Therefore endogenously released AA induced by the co-stimulation of NMDA and cholinergic receptors seems to be involved, at least partly, in the release of DA.     

Spinal cord regeneration in a tail autotomizing urodele

Adult urodele amphibians possess extensive regenerative abilities, including lens, jaws, limbs, and tails. In this study, we examined the cellular events and time course of spinal cord regeneration in a species, Plethodon cinereus, that has the ability to autotomize its tail as an antipredator strategy. We propose that this species may have enhanced regenerative abilities as further coadaptations with this antipredator strategy. We examined the expression of nestin, vimentin, and glial fibrillary acidic protein (GFAP) after autotomy as markers of neural precursor cells and astroglia; we also traced the appearance of new neurons using 5‐bromo‐2′‐deoxyuridine/neuronal nuclei (BrdU/NeuN) double labeling. As expected, the regenerating ependymal tube was a major source of new neurons; however, the spinal cord cranial to the plane of autotomy showed significant mitotic activity, more extensive than what is reported for other urodeles that cannot autotomize their tails. In addition, this species shows upregulation of nestin, vimentin, and GFAP within days after tail autotomy; further, this expression is upregulated within the spinal cord cranial to the plane of autotomy, not just within the extending ependymal tube, as reported in other urodeles. We suggest that enhanced survival of the spinal cord cranial to autotomy allows this portion to participate in the enhanced recovery and regeneration of the spinal cord. J. Morphol. 2011. © 2011 Wiley Periodicals, Inc.