Improvement of ethanol productivity and energy efficiency by degradation of inhibitors using recombinant Zymomonas mobilis (pHW20a-fdh).

Toxic compounds, such as formic acid, furfural, and hydroxymethylfurfural (HMF) generated during pretreatment of corn stover (CS) at high temperature and low pH, inhibit growth of Zymomonas mobilis and lower the conversion efficiency of CS to biofuel and other products. The inhibition of toxic compounds is considered as one of the major technical barriers in the lignocellulose bioconversion. In order to detoxify and/or degrade these toxic compounds by the model ethanologenic strain Z. mobilis itself in situ the fermentation medium, we constructed a recombinant Z. mobilis ZM4 (pHW20a-fdh) strain that is capable of degrading toxic inhibitor, formate. This is accomplished by cloning heterologous formate dehydrogenase gene (fdh) from Saccharomyces cerevisiae and by coupling this reaction of NADH regeneration reaction system with furfural and HMF degradation in the recombinant Z. mobilis strain. The NADH regeneration reaction also improved both the energy efficiency and cell physiological activity of the recombinant organism, which were definitely confirmed by the improved cell growth, ethanol yield, and ethanol productivity during fermentation with CS hydrolysate.

A review of long-term change in surface water natural organic matter concentration in the northern hemisphere and the implications for drinking water treatment.

Reduced atmospheric acid deposition has given rise to recovery from acidification - defined as increasing pH, acid neutralization capacity (ANC), or alkalinity in surface waters. Strong evidence of recovery has been reported across North America and Europe, driving chemical responses. The primary chemical responses identified in this review were increasing concentration and changing character of natural organic matter (NOM) towards predominantly hydrophobic nature. The concentration of NOM also influenced trace metal cycling as many browning surface waters also reported increases in Fe and Al. Further, climate change and other factors (e.g., changing land use) act in concert with reductions in atmospheric deposition to contribute to widespread browning and will have a more pronounced effect as deposition stabilizes. The observed water quality trends have presented challenges for drinking water treatment (e.g., increased chemical dosing, poor filter operations, formation of disinfection by-products) and many facilities may be under designed as a result. This comprehensive review has identified key research areas to be addressed, including 1) a need for comprehensive monitoring programs (e.g., larger timescales; consistency in measurements) to assess climate change impacts on recovery responses and NOM dynamics, and 2) a better understanding of drinking water treatment vulnerabilities and the transition towards robust treatment technologies and solutions that can adapt to climate change and other drivers of changing water quality.

Epigenetic effects of folate and related B vitamins on brain health throughout life: Scientific substantiation and translation of the evidence for health improvement strategies.

Suboptimal status of folate and/or interrelated B vitamins (B12 , B6 and riboflavin) can perturb one-carbon metabolism and adversely affect brain development in early life and brain function in later life. Human studies show that maternal folate status during pregnancy is associated with cognitive development in the child, whilst optimal B vitamin status may help to prevent cognitive dysfunction in later life. The biological mechanisms explaining these relationships are not clear but may involve folate-related DNA methylation of epigenetically controlled genes related to brain development and function. A better understanding of the mechanisms linking these B vitamins and the epigenome with brain health at critical stages of the lifecycle is necessary to support evidence-based health improvement strategies. The EpiBrain project, a transnational collaboration involving partners in the United Kingdom, Canada and Spain, is investigating the nutrition-epigenome-brain relationship, particularly focussing on folate-related epigenetic effects in relation to brain health outcomes. We are conducting new epigenetics analysis on bio-banked samples from existing well-characterised cohorts and randomised trials conducted in pregnancy and later life. Dietary, nutrient biomarker and epigenetic data will be linked with brain outcomes in children and older adults. In addition, we will investigate the nutrition-epigenome-brain relationship in B vitamin intervention trial participants using magnetoencephalography, a state-of-the-art neuroimaging modality to assess neuronal functioning. The project outcomes will provide an improved understanding of the role of folate and related B vitamins in brain health, and the epigenetic mechanisms involved. The results are expected to provide scientific substantiation to support nutritional strategies for better brain health across the lifecycle.

APDM gait and balance measures fail to predict symptom progression rate in Parkinson's disease.

Parkinson's disease (PD) results in progressively worsening gait and balance dysfunction that can be measured using computerized devices. We utilized the longitudinal database of the Parkinson's Disease Biomarker Program to determine if baseline gait and balance measures predict future rates of symptom progression. We included 230, 222, 164, and 177 PD subjects with 6, 12, 18, and 24 months of follow-up, respectively, and we defined progression as worsening of the following clinical parameters: MDS-UPDRS total score, Montreal Cognitive Assessment, PDQ-39 mobility subscale, levodopa equivalent daily dose, Schwab and England score, and global composite outcome. We developed ridge regression models to independently estimate how each gait or balance measure, or combination of measures, predicted progression. The accuracy of each ridge regression model was calculated by cross-validation in which 90% of the data were used to estimate the ridge regression model which was then tested on the 10% of data left out. While the models modestly predicted change in outcomes at the 6-month follow-up visit (accuracy in the range of 66-71%) there was no change in the outcome variables during this short follow-up (median change in MDS-UPDRS total score = 0 and change in LEDD = 0). At follow-up periods of 12, 18, and 24 months, the models failed to predict change (accuracy in the held-out sets ranged from 42 to 60%). We conclude that this set of computerized gait and balance measures performed at baseline is unlikely to help predict future disease progression in PD. Research scientists must continue to search for progression predictors to enhance the performance of disease modifying clinical trials.

Design and construction of improved new vectors for Zymomonas mobilis recombinants.

Zymomonas mobilis is a very important gram-negative bacterium having a potential application to simultaneous co-production of biofuel and other high value-added products through biorefinery process technology development. Up to now, pLOI193 has been used as the plasmid of choice for Z. mobilis strains. However, its application has been limited due to its relatively low transformation efficiency, a large plasmid size (13.4 kb), and limited choice of cloning sites for gene manipulations. Some of these limitations can be overcome by the newly designed and constructed plasmid pHW20a, which provides significantly higher transformation efficiency (about two orders of magnitude greater), better stability (for at least 120 generation times), and an ease of gene manipulations. The pHW20a contains three complete cis-acting genes (repA, repB, and repC) encoding the Rep proteins for primosome formation. It has the origin of replication (oriV) to ensure replication in gram-negative bacteria, two mob genes that enhances transformation efficiency, a screening marker (lacZα), expanded multiple cloning sites (MCS) that enables easy gene manipulation, and the tetracycline resistance gene (tc(r) ). The utility of screening marker, lacZα with MCS, was confirmed by the blue-white screening test. Several examples of applications of gene expression in Z. mobilis ZM4 have been demonstrated in this article by using several new pHW20a-derived plasmids and expressing the homologous genes (gfo and ppc) and the heterologous genes (bglA, mdh, and fdh1). The results show that pHW20a is a very useful new vector for construction of new Z. mobilis recombinant strains that will enable simultaneous co-production of biofuel and high value added products.

Tick paralysis in a free-ranging bobcat (Lynx rufus).

CASE DESCRIPTION: A free-ranging male bobcat (Lynx rufus) was evaluated because of signs of pelvic limb paralysis. CLINICAL FINDINGS: Physical examination of the anesthetized animal revealed tick infestation, normal mentation, and a lack of evidence of traumatic injuries. Radiography revealed no clinically relevant abnormalities. Hematologic analysis results were generally unremarkable, and serologic tests for exposure to feline coronavirus, FeLV, FIV, and Toxoplasma gondii were negative. Results of PCR assays for flea- and common tick-borne organisms other than Bartonella clarridgeiae were negative. TREATMENT AND OUTCOME: Ticks were manually removed, and the patient received supportive care and fipronil treatment. The bobcat made a full recovery within 72 hours after treatment for ticks, and a presumptive diagnosis of tick paralysis was made. Identified tick species included Dermacenter variabilis, Amblyomma americanum, and Ixodes scapularis. CLINICAL RELEVANCE: To the authors' knowledge, tick paralysis has not previously been reported in felids outside Australia. This disease should be considered a differential diagnosis in felids, including exotic cats, with signs of neuromuscular disease of unknown etiopathogenesis.

Intergenerational transmission of adverse childhood experiences via maternal depression and anxiety and moderation by child sex.

Adverse childhood experiences (ACEs) of parents are associated with a variety of negative health outcomes in offspring. Little is known about the mechanisms by which ACEs are transmitted to the next generation. Given that maternal depression and anxiety are related to ACEs and negatively affect children's behaviour, these exposures may be pathways between maternal ACEs and child psychopathology. Child sex may modify these associations. Our objectives were to determine: (1) the association between ACEs and children's behaviour, (2) whether maternal symptoms of prenatal and postnatal depression and anxiety mediate the relationship between maternal ACEs and children's behaviour, and (3) whether these relationships are moderated by child sex. Pearson correlations and latent path analyses were undertaken using data from 907 children and their mothers enrolled the Alberta Pregnancy Outcomes and Nutrition study. Overall, maternal ACEs were associated with symptoms of anxiety and depression during the perinatal period, and externalizing problems in children. Furthermore, we observed indirect associations between maternal ACEs and children's internalizing and externalizing problems via maternal anxiety and depression. Sex differences were observed, with boys demonstrating greater vulnerability to the indirect effects of maternal ACEs via both anxiety and depression. Findings suggest that maternal mental health may be a mechanism by which maternal early life adversity is transmitted to children, especially boys. Further research is needed to determine if targeted interventions with women who have both high ACEs and mental health problems can prevent or ameliorate the effects of ACEs on children's behavioural psychopathology.

Co-occurring disorders: a possible key to visual perceptual deficits in children with developmental coordination disorder?

A study was conducted to examine how visual perceptual functioning in children with DCD may be influenced by co-occurring learning problems such as reading disabilities (RD) and/or attention deficit hyperactivity disorder (ADHD). Participants included seven groups of children: 27 children with DCD only, 11 with ADHD only, 14 with RD only, 63 with DCD and at least one other disorder (i.e., DCD + ADHD, DCD + RD, DCD + ADHD + RD), and 73 typically developing controls. Visual perceptual skills were assessed using the Test of Visual Perceptual Skills (TVPS) and the Rey Osterreith Complex Figure (ROCF; copy and delayed recall). Children with DCD and at least one other disorder were found to have impairments on the TVPS compared to children with DCD only, ADHD only, and typically developing controls, particularly on subtests assessing visual memory. On the ROCF, children with DCD and at least one other disorder scored significantly lower than children with ADHD only or RD only. Children with DCD plus one other disorder were then subdivided into three groups: DCD + ADHD, DCD + RD, and DCD + ADHD + RD and compared to children with DCD only, ADHD only, and RD only. Results indicated that children with DCD + ADHD + RD had significant impairments on the TVPS compared to children with DCD only and children with ADHD only. On the ROCF, children with DCD + ADHD + RD scored significantly lower than all of the groups, except the DCD+RD group. These findings suggest that DCD on its own is not associated with visual perceptual problems; rather, it is the presence of co-occurring disorders that is a possible key to visual perceptual deficits in children with DCD. The number of co-occurring disorders present with DCD is associated with the severity of the visual perceptual dysfunction. Deficits in visual memory skills appear to be a specific area of difficulty for children with DCD and co-occurring RD and/or ADHD.

Carbon and energy balances of glucose fermentation with hydrogenproducing bacterium Citrobacter amalonaticus Y19.

For the newly isolated H2-producing chemoheterotrophic bacterium Citrobacter amalonaticus Y19, anaerobic glucose metabolism was studied in batch cultivation at varying initial glucose concentrations (3.5- 9.5 g/l). The carbon-mass and energy balances were determined and utilized to analyze the carbon metabolic-pathways network. The analyses revealed (a) variable production of major metabolites (H2, ethanol, acetate, lactate, CO2, and cell mass) depending on initial glucose levels; (b) influence of NADH regeneration on the production of acetate, lactate, and ethanol; and (c) influence of the molar production of ATP on the production of biomass. The results reported in this paper suggest how the carbon metabolic pathway(s) should be designed for optimal H2 production, especially at high glucose concentrations, such as by blocking the carbon flux via lactate dehydrogenase from the pyruvate node.

Substrate specificity of nonribosomal peptide synthetase modules responsible for the biosynthesis of the oligopeptide moiety of cephabacin in Lysobacter lactamgenus.

Lysobacter lactamgenus produces cephabacins, a class of beta-lactam antibiotics which have an oligopeptide moiety attached to the cephem ring at the C-3 position. The nonribosomal peptide synthetase (NRPS) system, which comprises four distinct modules, is required for the biosynthesis of this short oligopeptide, when one takes the chemical structure of these antibiotics into consideration. The cpbI gene, which has been identified in a region upstream of the pcbAB gene, encodes the NRPS - polyketide synthase hybrid complex, where NRPS is composed of three modules, while the cpbK gene -- which has been reported as being upstream of cpbI-- comprises a single NRPS module. An in silico protein analysis was able to partially reveal the specificity of each module. The four recombinant adenylation (A) domains from each NRPS module were heterologously expressed in Escherichia coli and purified. Biochemical data from ATP-PPi exchange assays indicated that L-arginine was an effective substrate for the A1 domain, while the A2, A3 and A4 domains activated L-alanine. These findings are in an agreement with the known chemical structure of cephabacins, as well as with the anticipated substrate specificity of the NRPS modules in CpbI and CpbK, which are involved in the assembly of the tetrapeptide at the C-3 position.

Adverse reactions during stem cell infusion in children treated with autologous and allogeneic stem cell transplantation.

Adverse reactions (ARs) during the infusion of cellular therapy products (CTPs) are common in patients undergoing hematopoietic stem cell transplantation (HSCT). We retrospectively studied pediatric patients undergoing autologous and allogeneic HSCT to determine the incidence and grade of ARs during stem cell infusion and their predictors. We analyzed data from 213 patients (120 allogeneic and 93 autologous) who received at least 1 CTP, totaling 361 infusion episodes. Serious ARs, defined as grade 2 and 3, occurred in 25 and 11% of infusions, respectively. No grade 4 or 5 ARs were noted. Independent risk factors for developing a serious AR included stem cell source (PBSC vs marrow (odds ratio (OR) 1.8, 95% confidence interval (CI): 0.4-9); cord vs marrow (OR 7.3, 95% CI: 1.3-40), overall P=0.0001) but manipulated CTPs were protective (OR 0.4, 95% CI: 0.2-0.7, P=0.004). Unlike previous adult studies, WBC and granulocyte content were not found to be risk factors in this pediatric population. These data suggest that children tolerate higher WBC content during infusion of CTPs and support the use of manipulated CTP, as indicated, to reduce the risk of adverse infusion reactions.

Antidepressants in 'depressed' schizophrenic inpatients. A controlled trial.

Fifty-eight actively psychotic inpatients who initially met criteria for long-standing schizophrenia and subsequently met Research Diagnostic Criteria for a current episode of schizoaffective disorder (mainly schizophrenic) with a depressive syndrome, and who scored at least 30 (mean = 55, SEM = 1.6) on the Brief Psychiatric Rating Scale and 17 (mean = 23, SEM = 0.7) on the Hamilton Rating Scale for Depression, were treated for 5 weeks with haloperidol hydrochloride and benztropine. Haloperidol and benztropine treatment was continued, while those patients who consistently scored greater than 17 on the Hamilton Rating Scale for Depression were randomly assigned to the following double-blind treatment groups for 4 weeks: adjunctive amitriptyline hydrochloride, desipramine hydrochloride, or placebo. Adjunctive desipramine or amitriptyline showed no significant therapeutic advantage, when compared with haloperidol and placebo, on the Brief Psychiatric Rating Scale or the Hamilton Rating Scale for Depression. After 4 weeks of combine therapy, patients receiving adjunctive amitriptyline or desipramine, as compared with those receiving adjunctive placebo, tended to score higher on the Brief Psychiatric Rating Scale hallucinatory behavior item and on the thinking disturbance factor than patients receiving placebo. These results suggest that adjunctive antidepressants are not indicated for the treatment of depressive symptoms in actively psychotic schizophrenic inpatients. Adjunctive antidepressants may retard the rate of resolution of psychosis in this population.

Cell-type specific organization of glycine receptor clusters in the mammalian spinal cord.

Glycinergic synapses play a major role in shaping the activity of spinal cord neurons. The spatial organization of postsynaptic receptors is likely to determine many functional parameters at these synapses and is probably related to the integrative capabilities of different neurons. In the present study, we have investigated the organization of gephyrin expression along the dendritic membranes of alpha- and gamma-motoneurons, Ia inhibitory interneurons, and Renshaw cells. Gephyrin is a protein responsible for the postsynaptic clustering of glycine receptors, and the features of gephyrin and glycine receptor alpha(1)-subunit immunofluorescent clusters displayed similar characteristics on ventral horn spinal neurons. However, the density of clusters and their topographical organization and architecture varied widely in different neurons and in different dendritic regions. For motoneurons and Ia inhibitory interneurons, cluster size and complexity increased with distance from the soma, perhaps as a mechanism to enhance the influence of distal synapses. Renshaw cells were special in that they displayed an abundant complement of large and morphologically complex clusters concentrated in their somas and proximal dendrites. Serial electron microscopy confirmed that the various immunoreactivity patterns observed with immunofluorescence accurately parallel the variable organization of pre- and postsynaptic active zones of glycinergic synapses. Finally, synaptic boutons from single-labeled axons of glycinergic neurons (Ia inhibitory interneurons) were also associated with postsynaptic receptor clusters of variable shapes and configurations. Our results indicate that mechanisms regulating receptor clustering do so primarily in the context of the postsynaptic neuron identity and localization in the dendritic arbor.

Factors regulating AMPA-type glutamate receptor subunit changes induced by sciatic nerve injury in rats.

Excitatory glutamatergic neurotransmission at Ia afferent-motoneuron synapses is enhanced shortly after physically severing or blocking impulse propagation of the afferent and/or motoneuron axons. We considered the possibility that these synaptic changes occur because of alterations in the number or properties of motoneuron alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors. Therefore, we quantitatively analyzed glutamate receptor (GluR)1, GluR2/3, and GluR4 AMPA subunit immunoreactivity (ir) in motoneurons 3, 7, or 14 days after axotomy or continuous tetrodotoxin (TTX) block of the sciatic nerve. GluR1-ir remained low in experimental and control motoneurons with either treatment and at any date. However, there was a large reduction of GluR2/3-ir (peak at 7 days >60% reduced) and a smaller, but statistically significant, reduction of GluR4-ir (around 10% reduction at days 3, 7, and 14) in axotomized motoneurons. TTX sciatic blockade did not affect AMPA subunit immunostainings. Axonal injury or interruption of the trophic interaction between muscle and spinal cord, but not activity disruption, appears therefore more likely responsible for altering AMPA subunit immunoreactivity in motoneurons. These findings also suggest that synaptic plasticity induced by axotomy or TTX block, although similar in the first week, could be related to different mechanisms. The effects of axotomy or TTX block on motoneuron expression of the metabotropic glutamate receptor mGluR1a were also studied. mGluR1a-ir was also strongly decreased after axotomy but not after TTX treatment. The time course of the known stripping of synapses from the cell somas of axotomized motoneurons was studied by using synaptophysin antibodies and compared with AMPA and mGluR1a receptor changes. Coverage by synaptophysin-ir boutons was only clearly decreased 14 days post axotomy and not at shorter intervals or after TTX block.

Distribution of 5-hydroxytryptamine-immunoreactive boutons on alpha-motoneurons in the lumbar spinal cord of adult cats.

Recent studies have shown that at least some of the functional effects of serotonin (5-HT) on motoneuron excitability are direct and are mediated via postsynaptic 5-HT receptors on motoneurons. To determine the spatial distribution of direct inputs from the serotonin system on the proximal and distal dendrites of individual motoneurons, we examined identified motoneurons in vivo with a combination of immunohistochemical localization of 5-HT-immunoreactive boutons and intracellular staining with horseradish peroxidase. Seventeen intracellularly stained motoneurons from 12 adult cats were analyzed with light microscopy. Quantitative analysis of 5-HT boutons apposed to dendrites of five representative motoneurons that were entirely reconstructed in three dimensions (each from the lumbosacral spinal cord of a different animal) revealed a total of 7,848 contacts (1,570+/-487 contacts/postsynaptic neuron; mean +/- SD) over the dendrites of these cells. Analysis of contacts on the soma of two of these cells, and on the somas of an additional 12 intracellularly stained motoneurons, revealed a wide range of somatic contacts (11-211 contacts/cell) on motoneuron cell bodies, with an average of 52 contacts/cell. These results indicate that the vast majority of 5-HT-immunoreactive boutons are apposed to dendritic branches rather than to the somatic surface of motoneurons. The spatial distribution of contacts essentially matched the distribution of surface membrane area of the postsynaptic neuron, resulting in a relatively uniform density of contacts (<1/100 microm2) on proximal and distal dendrites. Consequently, the frequency of contacts was higher on the proximal dendritic compartments where available membrane area is greater. There was no preferential distribution of contacts to particular dendrites. Light/electron microscopic correlations were performed on 21 boutons that contacted dendrites (n = 7) of three motoneurons from different animals. At the electron microscope level, most appositions (18/21; 85.7%) selected by our light microscopic criteria were confirmed as direct contacts when the 5-HT boutons were examined through serial sections. Synaptic junctions, generally small and symmetric, were positively identified in only a subset of these cases (n = 6; 28.6%), in part due to the obscuring effects of the peroxidase histochemical precipitate present in both pre- and postsynaptic profiles. A few 5-HT boutons (3/21; 14.3%) selected as contacts by our light microscopic criteria were in fact separated from the adjacent labeled dendrites; in two of these three cases, the separation was due to intrusion of very thin glial lamellae (<0.3 microm in cross section). These results indicate that the bulbospinal serotonergic system(s) provide a significant, direct synaptic input to spinal motoneurons that innervate hindlimb muscles. The nature of the modulatory actions exerted by such widespread synaptic inputs will affect all regions of the somatodendritic membrane and will ultimately depend on the nature of the 5-HT receptors present over different parts of the postsynaptic neuron's dendritic tree.

Methyl glyoxal bis guanylhydrazone abolition of the toxic action of spermidine on cells in culture.

Spermidine inhibits many cells in culture because amine oxidase in the serum converts spermidine to toxic products. Methyl glyoxal bis guanylhydrazone (Methyl GAG) inhibits cells in culture because it is a specific inhibitor of S-adenosylmethionine decarboxylase, preventing the conversion of putrescine to spermidine. When both spermidine and methyl GAG were added together, no inhibition was observed. The effect could be explained by the finding that methyl GAG was a powerful non-competitive inhibitor of the enzymatic oxidation of spermidine to acrolein.

The identification of a cell culture inhibitor in a tumour extract.

An extract of Harding-Passey mouse melanoma was found to inhibit the proliferation of the same cell line grown in culture when measured by both thymidine incorporation and by the increase in cell number. The active ingredient was purified by ultrafiltration, column chromatography and preparative electrophoresis. The purified material was identified by mass spectrometry and by gas chromatography as spermidine. The partially purified material reversed the methylglyoxal Bis-guanyl hydrazone (Methyl-GAG) inhibition of cultured cells to the same extent as spermidine. Very low concentrations of Methyl-GAG were found to suppress the spermidine inhibition of thymidine incorporation into cells. The inhibitor extracted from melanoma tumours behaved in the same way as spermidine at all Methyl-GAG concentrations. Thus, it is unlikely that the active ingredient in the biological extract is anything other than spermidine.

Inhibition of proliferation of cultured cells by polyamine and cysteine interaction.

Both L-cysteine and spermidine oxidation inhibited the proliferation of cultured cells when these reagents were added in low concentrations. Higher concentrations (above 1 mM) of cysteine were not cytotoxic. Furthermore, high concentrations of L-cysteine partially protected against spermidine oxidation toxicity. D-cysteine on its own behaved exactly the same as an equimolar concentration of L-cysteine, but instead of protecting against the effects of spermidine oxidation, the inhibition was enhanced. A possible mechanism for the interaction is discussed.

The effect of oxygen on the delay in the initiation of DNA synthesis after irradiation.

The effect of oxygen on cell cycle delay by low doses of radiation on synchronized Harding Passey melanoma cells has been studied. Cells were irradiated 5 h after subculturing into fresh medium, and the delay before the start of S was measured. DNA synthesis was measured by frequent pulse labeling of the cells with radioactive thymidine to obtain the S-phase profile. The amount by which the irradiated cells S-phase profile had to be moved in time so that both the ascending and descending portions of the first S phase overlayed that of the controls was used as a measure of the delay. The magnitude of the delay was exponentially related to radiation dose and the effect of irradiating in the absence of oxygen was a dose multiplying factor of 2.5. This was similar to the oxygen effect on survival for cells irradiated under the same conditions.

Downregulation of metabotropic glutamate receptor 1a in motoneurons after axotomy.

Axotomized motoneurons display drastic modifications in synaptic structure and function related to their disconnection from the periphery and establishment of a regenerative metabolic functional mode. The molecular basis of these modifications is not fully understood. Here we describe changes in metabotropic glutamate receptor 1a (mGluR1a)-immunoreactivity 3, 7 or 14 days after unilateral aciatic transection. mGluR1a-immunoreactivity was distributed throughout the somatic cytoplasm and somatodendritic membrane of uninjured motoneurons and was significantly reduced in axotomized motoneurons. This reduction was observed at 3 days and grew progressively over 2 weeks. These findings suggest that downregulation of mGluR1a could contribute to reduced excitatory neurotransmission in axotomized motoneurons.