Ventral Lesions Research Articles

Role of Striatal Cholinergic Interneurons in Set-Shifting in the Rat.

The ability to change strategies in different contexts is a form of behavioral flexibility that is crucial for adaptive behavior. The striatum has been shown to contribute to certain forms of behavioral flexibility such as reversal learning. Here we report on the contribution of striatal cholinergic interneurons-a key element in the striatal neuronal circuit-to strategy set-shifting in which an attentional shift from one stimulus dimension to another is required. We made lesions of rat cholinergic interneurons in dorsomedial or ventral striatum using a specific immunotoxin and investigated the effects on set-shifting paradigms and on reversal learning. In shifting to a set that required attention to a previously irrelevant cue, lesions of dorsomedial striatum significantly increased the number of perseverative errors. In this condition, the number of never-reinforced errors was significantly decreased in both types of lesions. When shifting to a set that required attention to a novel cue, rats with ventral striatum lesions made more perseverative errors. Neither lesion impaired learning of the initial response strategy nor a subsequent switch to a new strategy when response choice was indicated by a previously relevant cue. Reversal learning was not affected. These results suggest that in set-shifting the striatal cholinergic interneurons play a fundamental role, which is dissociable between dorsomedial and ventral striatum depending on behavioral context. We propose a common mechanism in which cholinergic interneurons inhibit neurons representing the old strategy and enhance plasticity underlying exploration of a new rule.

The sigma agonist 1,3-di-o-tolyl-guanidine reduces the morphological and behavioral changes induced by neonatal ventral hippocampus lesion in rats.

Sigma (σ) receptors have generated a great deal of interest due to their possible role in psychosis, neuroprotection, and various other behaviors including addictive processes. Sigma receptors have been located in brain areas involved in motor functions, including the dopaminergic projections from the substantia nigra to the striatum. Evidence suggests that one of their major roles might be to regulate the activity of the glutamatergic system via the N-methyl-D-aspartate receptor. The sigma receptor agonist 1,3-di-o-tolyl-guanidine (DTG) was found to increase dopamine release in the striatum, nucleus accumbens, and prefrontal cortex, in a dose-dependent manner, after central as well as peripheral administration, suggesting a modulatory role of these receptors on the dopaminergic system. The present study examines whether chronic administration of the DTG sigma agonist induces neuromorphological and behavioral changes in neonatal ventral hippocampal lesioned (nVHL) rats as a neurodevelopmental model of schizophrenia. The results show that the DTG administration reduces the hyperlocomotor activity in nVHL rats and reverses the neuronal hypotrophy generated in nVHL rats in the prefrontal cortex, amygdala, and nucleus accumbens. Our results demonstrate that DTG, a sigma-1 receptor agonist, reverses some of the behavioral and neuromorphological effects of nVHL on the rat and supports the possibility that DTG may have beneficial effects in the management of symptoms of schizophrenia.

Posterior Cervical Microscopic Foraminotomy and Discectomy with Laser for Unilateral Radiculopathy.

Surgical decompression for cervical radiculopathy includes anterior cervical discectomy and fusion, anterior or posterior cervical foraminotomy, and cervical arthroplasty after decompression. The aim of this study was to evaluate the usefulness of a CO2 laser in posterior-approach surgery for unilateral cervical radiculopathy. From January 2006 to December 2008, 12 consecutive patients with unilateral cervical radiculopathy from either foraminal stenosis or disc herniation, which was confirmed with imaging studies, underwent posterior foraminotomy and discectomy with the use of a microscope and CO2 laser. For annulotomy and discectomy, we used about 300 joules of CO2 laser energy. Magnetic resonance imaging (MRI) was used to evaluate the extent of disc removal or foraminal decompression. Clinical outcome was evaluated by using visual analogue scale scores for radicular pain and Odom's criteria. For evaluation of spinal stability, cervical flexion and extension radiographs were obtained. Single-level foraminotomy was performed in 10 patients and two-level foraminotomies were performed in 2 patients. Preoperative radicular symptoms were improved immediately after surgery in all patients. No surgery-related complications developed in our cases. Postoperative MRI demonstrated effective decompression of ventral lesions and widened foraminal spaces in all cases. There was no development of cervical instability during the follow-up period. Posterior foraminotomy and discectomy using a microscope and CO2 laser is an effective surgical tool for unilateral cervical radiculopathy caused by lateral or foraminal disc herniations or spondylotic stenosis. Long-term follow-up with radiographs showed no significant kyphotic changes or spinal instability.

The role of the ventral dentate gyrus in anxiety-based behaviors

Dorsoventral lesion studies of the hippocampus (HPP) indicate that the dorsal axis is important for spatial processing and the ventral axis is important in anxiety and olfactory processes. There is some evidence that ventral CA3 and ventral CA1 subregions are important for cued retrieval in fear conditioning, which supports a ventral-anxiety relationship. However, the role of the ventral dentate gyrus (DG) in anxiety-based behaviors is less understood. Therefore, we used elevated plus and open field mazes to investigate the role of the ventral DG in the ability to modify behavior in potentially dangerous conditions and to clarify a few previous reports that ventral HPP lesions may induce hyperactivity. Rats with ventral DG lesions spent significantly more time in the open arms of the elevated plus maze and inner zone of the open field test than did controls and rats with dorsal DG lesions. Locomotor measures indicate that all rats traveled at similar rates in enclosed arms, as well as in open arms of the elevated plus maze and all groups traveled at similar rates in the open field test, which indicates that differences in exploration were not likely due to hyperactivity. The present study findings indicate that the ventral DG plays an important role in anxiety-based behaviors, such as preference for safer environments and the ability to modify exploratory behavior when in potentially dangerous environments and that the dorsal DG is not importantly involved in anxiety.

The monster we don't see: subclinical BRD in beef cattle.

Bovine respiratory disease (BRD) is the most expensive disease affecting United States cattle. Recently weaned calves are the focus of prevention and treatment research. Identifying affected cattle early in the course of BRD is difficult. Intervention during the early stages of BRD improves treatment outcomes; however, cattle as prey animals are excellent at hiding signs of disease, especially if the caregiver has not gained their trust. Depression, appetite loss, and changes in respiratory character are the principal signs used to identify BRD. Rectal temperatures from cattle pulled for treatment are a final measure of evaluation. Cattle suffering from subclinical BRD frequently escape identification and treatment. Observations of lungs at packing plants for anterior ventral (AV) lesions frequently document higher BRD incidence rates than observed pre-harvest, suggesting subclinical BRD is common. Data from numerous studies document lower average daily gains (ADG) from cattle with AV lung lesions at packing plants that were not treated for BRD compared with cattle with normal lungs. Scoring lung lesions at the packing plant can be a useful tool for gaining insight into BRD incidence. Data indicate that BRD lowers ADG by 0.2lbs on average, and lowers the USDA Quality Grade by 50 marbling points.

Please keep calm: investigating hippocampal function without stress.

Please keep calm: investigating hippocampal function without stress.

Haloperidol treatment at pre-exposure phase reduces the disturbance of latent inhibition in rats with neonatal ventral hippocampus lesions

Animals with neonatal ventral hippocampal lesions develop during or after adolescence abnormal behaviors related to schizophrenia such as anxiety and latent inhibition disruption. The aim of this study was to test whether haloperidol injection prior to pre-exposure session in the latent inhibition test would facilitate latent inhibition.Lesioned animals showed a significant decrease in the number and duration of social interactions, a decrease in the marbles buried, a significant increase in locomotor activity, and a disruption of latent inhibition. In the conditioned taste aversion test, injection of haloperidol produced the recovery of latent inhibition. These findings demonstrate that neonatal lidocaine lesion of the ventral hippocampus can induce behavioral changes related to schizophrenia, and injection of haloperidol, when restricted only to a three-day pre-exposure, is sufficient to facilitate latent inhibition.

Cannabinoids reward sensitivity in a neurodevelopmental animal model of schizophrenia: A brain stimulation reward study

The comorbidity schizophrenia and cannabis has a high prevalence. The consumption of cannabis is ten times higher among schizophrenia patients, suggesting that these patients could be differentially sensitive to its motivational effects. To study this question, we investigated the motivational effects of cannabinoid agonists using the brain stimulation reward paradigm and a neurodevelopmental model of schizophrenia: neonatal ventral hippocampus lesions (NVHL). Using the curve-shift paradigm, we first compared the effect single dose (0.75mg/kg) of amphetamine in sham and NVHL rats on reward and operant responding. Then, in different groups of NVHL and sham rats, we studied the effect of delta-9-tetrahydrocannabinnol (THC, 0.5mg/kg, i.p.) and WIN55,212-2 (WIN, 1 and 3mg/kg, i.p.) Rats were initially trained to self-administer an electrical stimulation to the posterio-medial mesencephalon. Once responding was stable, reward threshold defined as the frequency required to induce a half maximum response rate was measured before and after injection of the drug or the vehicle. Results show that amphetamine enhanced reward in sham and NVHL rats, an effect that was shorter in duration in NVHL rats. THC produced a weak attenuation of reward in sham rats while WIN produced a dose-dependent attenuation in NVHL; the attenuation effect of WIN was blocked by the cannabinoid antagonist, AM251. WIN also produced an attenuation of performance in sham and NVHL rats, and this effect was partially prevented by AM251. These results provide the additional evidence that the motivational effect of cannabinoids is altered in animals with a schizophrenia-like phenotype.

Transcondylar Fossa Approach for Cerebellopontine Angle and Ventral Brainstem Lesions: Microsurgical Experiences and Avoidance of Complications

To treat the large tumors located in cerebellopontine angle (CPA) and vascular pathologies including aneurysms and dissection located around the ventral brainstem, transcondylar fossa approach (TCFA) has been regarded as less invasive one. Overall 10 patients had large tumors (D> 3 cm) including schwannomas (n = 8) and meningiomas (n = 2) located in the CPA and 17 patients had vascular pathologies including vertebra-basilar artery aneurysms (n = 14) and dissection (n = 3). Anatomical aspects of the condylar fossa, occipital condyle, and adjacent neurovascular structures were evaluated preoperatively and postoperatively using a three-dimensional computed tomography and magnetic resonance imaging. Gross-total removals in tumor patients achieved without resection of the occipital condyle. In 10 patients with saccular aneurysms, the aneurysms were clipped without resection of the occipital condyle and in 4 patients, partial resection of the condyle and jugular tubercle was necessary to obtain proximal control of the vertebral artery. We met two cases with vertebral artery injury and one case with postoperative cerebrospinal fluid. Transcondylar fossa approach was less invasive technique with minimal or no resection of the occipital condyle comparing with other approaches to ventral brainstem. To avoid complications, anatomical knowledge on the joint and the condylar veins should be reviewed.

Converging on a core cognitive deficit: the impact of various neurodevelopmental insults on cognitive control.

Despite substantial effort and immense need, the treatment options for major neuropsychiatric illnesses like schizophrenia are limited and largely ineffective at improving the most debilitating cognitive symptoms that are central to mental illness. These symptoms include cognitive control deficits, the inability to selectively use information that is currently relevant and ignore what is currently irrelevant. Contemporary attempts to accelerate progress are in part founded on an effort to reconceptualize neuropsychiatric illness as a disorder of neural development. This neuro-developmental framework emphasizes abnormal neural circuits on the one hand, and on the other, it suggests there are therapeutic opportunities to exploit the developmental processes of excitatory neuron pruning, inhibitory neuron proliferation, elaboration of myelination, and other circuit refinements that extend through adolescence and into early adulthood. We have crafted a preclinical research program aimed at cognition failures that may be relevant to mental illness. By working with a variety of neurodevelopmental rodent models, we strive to identify a common pathophysiology that underlies cognitive control failure as well as a common strategy for improving cognition in the face of neural circuit abnormalities. Here we review our work to characterize cognitive control deficits in rats with a neonatal ventral hippocampus lesion and rats that were exposed to Methylazoxymethanol acetate (MAM) in utero. We review our findings as they pertain to early developmental processes, including neurogenesis, as well as the power of cognitive experience to refine neural circuit function within the mature and maturing brain's cognitive circuitry.

Cervical perimedullary arteriovenous shunts: a study of 22 consecutive cases with a focus on angioarchitecture and surgical approaches.

Reports of cervical perimedullary arteriovenous shunt (PMAVS) are limited, and treatment strategies have not been established. To describe angioarchitecture and optimal treatment strategies for cervical PMAVS. We treated 22 patients with cervical PMAVS between 2000 and 2012 (8 women and 14 men; age, 9-80 years). According to the classification, our patients included type IVa (4 patients), type IVb (16 patients), and type IVc (2 patients). Seventeen patients presented with subarachnoid hemorrhage. A total of 41 shunting points were localized in 22 patients, of which 34 points were located ventral or ventrolateral to the spinal cord. The anterior spinal artery (ASA) contributed to the shunts in 16 patients. Aneurysm formation was identified in 8 patients. Endovascular treatment was attempted in 3 patients, resulting in complete obliteration in 1 patient (type IVc). Overall, 21 patients underwent open surgery. An anterior approach with corpectomy was elected for 2 patients; the other 19 patients underwent the posterior approaches using indocyanine green videoangiography, intraoperative angiography, endoscopy (8 patients), and neuromonitoring. Twenty patients were rated as having a good recovery at 6 months after surgery. No recurrence was observed in any patients during the follow-up (mean, 59.7 months). Shunting points of the cervical PMAVS were predominantly located ventral or ventrolateral to the spinal cord and were often fed by the ASA. Even for ventral lesions, posterior exposure assisted with neuromonitoring and endoscopy, and intraoperative angiography provided a view sufficient to understand the relationships between the shunts and the ASA and contributed to good surgical outcomes.

Animals with a schizophrenia-like phenotype are differentially sensitive to the motivational effects of cannabinoid agonists in conditioned place preference

Cannabis is the most consumed illicit drug worldwide, but among patients with a diagnosis of schizophrenia, this consumption is higher suggesting that they are differentially sensitive to cannabis. We chose to study this problematic using a neurodevelopmental model of schizophrenia: neonatal ventral hippocampus lesions (NVHL). In a first study, we compared the locomotor response to novelty, a mild stress and two doses of amphetamine (0.75 and 1.5 mg/kg) in sham and NVHL rats at post-natal day 35 (PD35) or 56 (PD56). In a second study, we investigated the valence of the motivational effect of Delta-9-tetrahydrocannabinnol (THC, 0.5 mg/kg, i.p.) and the cannabinoid receptor agonist, WIN55,212-2 (WIN, 1 mg/kg, i.p.), using the conditioned place preference paradigm; we used a biased procedure that comprised 12 days of testing with 3 paired-conditioning. The effects of this dose of WIN were also measured on locomotor activity. Results confirmed that the adult NVHL animals displayed a stronger locomotor response to the two doses of amphetamine, but not to novelty and a mild stress. In adult NVHL, but not sham animals, WIN stimulated locomotor activity and produced a conditioned place aversion. At the dose tested, THC tended to produce an aversion in adult sham but not NVHL animals. Taken together these findings show that adult animals with a schizophrenia-like phenotype are differentially sensitive to the motivational effect of cannabinoids.

The role of the ventral dentate gyrus in olfactory pattern separation

Dorsoventral lesion studies of the hippocampus have indicated that the dorsal axis of the hippocampus is important for spatial processing and the ventral axis of the hippocampus is important for olfactory learning and memory and anxiety. There is some evidence to suggest that the ventral CA3 and ventral CA1 conduct parallel processes for pattern completion and temporal processing, respectively. Studies have indicated that the dorsal dentate gyrus (DG) is importantly involved in processes reflecting underlying pattern separation activity for spatial information. However, the ventral DG is less understood. The current study investigated the less-understood role of the ventral DG in olfactory pattern separation. A series of odor stimuli that varied on only one level, number of carbon chains (methyl groups), was used in a matching-to-sample paradigm in order to investigate ventral DG involvement in working memory for similar and less similar odors. Rats with ventral DG lesions were impaired at delays of 60 sec, but not at delays of 15 sec. A memory-based pattern separation effect was observed performance was poorest with only one carbon chain separation between trial odors and was highest for trials with four separations. The present study indicates that the ventral DG plays an important role in olfactory learning and memory processes for highly similar odors. The results also indicate a role for the ventral DG in pattern separation for odor information, which may have further implications for parallel processing across the dorsoventral axis for the DG in spatial (dorsal) and olfactory (ventral) pattern separation.

Targeting Neural Synchrony Deficits is Sufficient to Improve Cognition in a Schizophrenia-Related Neurodevelopmental Model

Cognitive symptoms are core features of mental disorders but procognitive treatments are limited. We have proposed a “discoordination” hypothesis that cognitive impairment results from aberrant coordination of neural activity. We reported that neonatal ventral hippocampus lesion (NVHL) rats, an established neurodevelopmental model of schizophrenia, have abnormal neural synchrony and cognitive deficits in the active place avoidance task. During stillness, we observed that cortical local field potentials sometimes resembled epileptiform spike-wave discharges with higher prevalence in NVHL rats, indicating abnormal neural synchrony due perhaps to imbalanced excitation–inhibition coupling. Here, within the context of the hypothesis, we investigated whether attenuating abnormal neural synchrony will improve cognition in NVHL rats. We report that: (1) inter-hippocampal synchrony in the theta and beta bands is correlated with active place avoidance performance; (2) the anticonvulsant ethosuximide attenuated the abnormal spike-wave activity, improved cognitive control, and reduced hyperlocomotion; (3) ethosuximide not only normalized the task-associated theta and beta synchrony between the two hippocampi but also increased synchrony between the medial prefrontal cortex and hippocampus above control levels; (4) the antipsychotic olanzapine was less effective at improving cognitive control and normalizing place avoidance-related inter-hippocampal neural synchrony, although it reduced hyperactivity; and (5) olanzapine caused an abnormal pattern of frequency-independent increases in neural synchrony, in both NVHL and control rats. These data suggest that normalizing aberrant neural synchrony can be beneficial and that drugs targeting the pathophysiology of abnormally coordinated neural activities may be a promising theoretical framework and strategy for developing treatments that improve cognition in neurodevelopmental disorders such as schizophrenia.

Evaluating negative-symptom-like behavioural changes in developmental models of schizophrenia

Many lines of evidence suggest that schizophrenia has a major developmental component and that environmental factors that disrupt key stages of development, such as maternal stress during pregnancy as a result of infection or malnutrition, can increase the risk of developing schizophrenia in later life. This review examines how non-clinical neurodevelopmental models pertinent to schizophrenia have been evaluated for their ability to reproduce behavioural deficits related to the negative symptoms of schizophrenia. The more frequently used are the prenatal application of the mitotoxic agent methylazoxymethanol, prenatal immune challenge and the neonatal ventral hippocampus lesion model. In general they have been extensively evaluated in models considered relevant to positive symptoms of schizophrenia. In contrast, very few studies have examined tests related to negative symptoms and, when they have, it has almost exclusively been a social interaction model. Other aspects related to negative symptoms such as anhedonia, affective flattening and avolition have almost never been studied. Further studies examining other components of negative symptomatology are needed to more clearly associate these deficits with a schizophrenia-like profile as social withdrawal is a hallmark of many disorders. Although there are no truly effective treatments for negative symptoms, better characterisation with a broader range of drugs used in schizophrenia will be necessary to better evaluate the utility of these models. In summary, developmental models of schizophrenia have been extensively studied as models of positive symptoms but, given the unmet need in the clinic, the same effort now needs to be made with regard to negative symptoms.

Chronic cerebrolysin administration attenuates neuronal abnormalities in the basolateral amygdala induced by neonatal ventral hippocampus lesion in the rat

The neonatal ventral hippocampal lesion (nVHL) has emerged as a model of schizophrenia-related behavior in the rat. Our previous report demonstrated that cerebrolysin (Cbl), a neuropeptide preparation which mimics the action of endogenous neurotrophic factors on brain protection and repair, promoted recovery of dendritic and neuronal damage of the prefrontal cortex and nucleus accumbens and behavioral improvements in postpubertal nVHL rats. We recently demonstrated that nVHL animals exhibit dendritic atrophy and spine loss in the basolateral amygdala (BLA). This study aimed to determine whether Cbl treatment was capable of reducing BLA neuronal alterations observed in nVHL rats. The morphological evaluation included examination of dendrites using the Golgi-Cox procedure and stereology to quantify the total cell number in BLA. Golgi-Cox staining revealed that nVHL induced dendritic retraction and spine loss in BLA pyramidal neurons. Stereological analysis demonstrated nVHL also produced a reduction in cells in BLA. Interestingly, repeated Cbl treatment ameliorated dendritic pathology and neuronal loss in the BLA of the nVHL rats. Our data show that Cbl may foster recovery of BLA damage in postpubertal nVHL rats and suggests that the use of neurotrophic agents for the management of some schizophrenia-related symptoms may present an alternative therapeutic pathway in these disorders.

The influence of cervical spine position on the three anterior endoscopic approaches to the craniovertebral junction: an imaging study

Background contextThree endoscopic anterior approaches, the transnasal, transoral, and transcervical approaches, are used for ventral lesions of the craniovertebral junction and have been compared regarding surgical working distances and approach angles. However, how the position of the cervical spine influences the depths of surgical corridors and approach angles for the three approaches has not been evaluated. PurposeTo evaluate the depths of surgical corridors and the approach angles for the three endoscopic approaches, taking the influence of cervical spine position into account. Study designA radiographic study comparing three anterior endoscopic approaches to the craniovertebral junction. Patient sampleCervical extension and flexion radiographs for 34 patients and cross-sectional computed tomography scans for 30 additional patients were assessed. Outcome measuresThe depths of the surgical corridors and the approach angles for the three endoscopic approaches in the midsagittal planes. MethodsWe determined the mean angles of the surgical trajectories for the endoscopic transoral and transcervical approaches on cervical extension and flexion radiographs. In addition, we measured the depths of the surgical corridors and the approach angles for the three approaches in the midsagittal plane. ResultsThe average depths of surgical corridors were as follows: endonasal, 93.65 mm; transoral, 85.27 mm; transcervical, 62.97 mm (in extension). The average approach angles were as follows: endonasal, 31.22°; transoral, 30.87°; transcervical, 36.58° (in extension). ConclusionsThe position of the cervical spine does not influence the surgical convenience of the endoscopic transnasal approach, but it can influence the endoscopic transoral and transcervical approaches, especially the latter. The endoscopic transcervical approach offers several advantages over the endoscopic transoral and endonasal approaches.

Chronic dermatitis caused by Lactobacillus jensenii infection in a blue and gold macaw (Ara ararauna)

A 5-year-old sexually intact female blue and gold macaw (Ara ararauna) was evaluated because of a swelling on the right side of the face and irritated area on the ventral aspect of the keel. Clinical findings were consistent with dermatitis (right facial lesion) and a coalescing subdermal granuloma (ventral keel lesion). Hematologic analysis revealed monocytosis and mild anemia. Histologic evaluation of the ventral keel lesion revealed evidence of chronic heterophilic dermatitis with multinucleated giant cells and bacterial rods and cocci. An unspeciated gram-positive rod-shaped bacterium was isolated via aerobic bacterial culture. Results of bacterial biochemical tests suggested the organism was a type of Actinomyces. A 16S rRNA gene sequence analysis was performed; results indicated the organism was Lactobacillus jensenii. Extensive surgical debridement of the branching granuloma, which extended throughout the length of the keel, followed by long-term treatment with ciprofloxacin and clindamycin provided full resolution of clinical signs. No recrudescence of clinical signs was evident for up to 18 months after the initial evaluation. To the authors' knowledge, this is the first report of Lactobacillus-associated dermatitis or subdermal granuloma in the scientific literature and the second report of L jensenii in avian species. Use of 16S rRNA gene sequence analysis was instrumental in the identification of this fastidious organism, indicating the method's usefulness as a diagnostic tool.

The role of human ventral visual cortex in motion perception

Visual motion perception is fundamental to many aspects of visual perception. Visual motion perception has long been associated with the dorsal (parietal) pathway and the involvement of the ventral ‘form’ (temporal) visual pathway has not been considered critical for normal motion perception. Here, we evaluated this view by examining whether circumscribed damage to ventral visual cortex impaired motion perception. The perception of motion in basic, non-form tasks (motion coherence and motion detection) and complex structure-from-motion, for a wide range of motion speeds, all centrally displayed, was assessed in five patients with a circumscribed lesion to either the right or left ventral visual pathway. Patients with a right, but not with a left, ventral visual lesion displayed widespread impairments in central motion perception even for non-form motion, for both slow and for fast speeds, and this held true independent of the integrity of areas MT/V5, V3A or parietal regions. In contrast with the traditional view in which only the dorsal visual stream is critical for motion perception, these novel findings implicate a more distributed circuit in which the integrity of the right ventral visual pathway is also necessary even for the perception of non-form motion.

Neuronal Loss and Decreased GLT-1 Expression Observed in the Spinal Cord of Pembroke Welsh Corgi Dogs With Canine Degenerative Myelopathy

Canine degenerative myelopathy (DM) is a progressive neurodegenerative disease that is frequently found in Pembroke Welsh Corgi (PWC) dogs. Canine DM is potentially a spontaneous animal model for human amyotrophic lateral sclerosis (ALS) because of similar lesions and the involvement of superoxide dismutase 1 (SOD1) mutation. However, the ventral horn lesion in DM has not been characterized in detail. Glutamate excitotoxicity due to deficiency of the glutamine-glutamate cycle has been implicated in neuron death in ALS. Thus, we examined 5 PWC dogs with an SOD1 mutation that were affected by DM, 5 non-DM PWC dogs, and 5 Beagle dogs without neurologic signs to assess the neuronal changes and the expression levels of 2 glial excitatory amino acid transporters (glutamate transporter 1 [GLT-1] and glutamate/aspartate transporter [GLAST]). The number of neurons in the spinal ventral horns of the DM dogs was significantly decreased, whereas no change was found in the cell size. Chromatolysis, lipofuscin-laden neurons, and marked synapse loss were also observed. GLT-1 expression was strikingly decreased in DM dogs, whereas GLAST expression showed no significant change. The results indicate that excitotoxicity related to the reduced expression of GLT-1, but not GLAST, may be involved in neuron loss in DM, as in human ALS, whereas intraneuronal events may differ between the 2 diseases.