Role of NMDA receptor activation in serotonin agonist-induced air-stepping in paraplegic mice

Guertin, Pierre A.

doi:10.1038/sj.sc.3101580

Cited by 34 publications

(51 citation statements)

References 28 publications

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“…Previous studies have shown that quipazine improves treadmill locomotion in adult chronic spinal cats (Barbeau and Rossignol, 1990;Brustein and Rossignol, 1999) and rats (FeraboliLohnherr et al, 1999;Antri et al, 2002), and recently, similar findings were reported for spinal mice (Guertin, 2004). We hypothesized that quipazine acutely elevates the sensitivity of the spinal locomotor circuits to proprioceptive inputs, thereby facilitating locomotor drive patterning when the spinal cord is presented with appropriate sensory cues.…”

Section: Introductionmentioning

confidence: 68%

“…Data to date suggest, however, that, in the absence of any pharmacological intervention, the level of recovery is lower in smaller species such as rats (de Leon et al, 2002) and mice (Guertin, 2004) compared with cats. Although there is one report of significant spontaneous recovery in complete spinal mice without any pharmacological intervention (Leblond et al, 2003), we have been unable to duplicate these observations.…”

Section: Introductionmentioning

confidence: 99%

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Spinal Cord-Transected Mice Learn to Step in Response to Quipazine Treatment and Robotic Training

Fong¹,

Cai²,

Otoshi³

et al. 2005

J. Neurosci.

131

126

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In the present study, concurrent treatment with robotic step training and a serotonin agonist, quipazine, generated significant recovery of locomotor function in complete spinal cord-transected mice (T7-T9) that otherwise could not step. The extent of recovery achieved when these treatments were combined exceeded that obtained when either treatment was applied independently. We quantitatively analyzed the stepping characteristics of spinal mice after alternatively administering no training, manual training, robotic training, quipazine treatment, or a combination of robotic training with quipazine treatment, to examine the mechanisms by which training and quipazine treatment promote functional recovery. Using fast Fourier transform and principal components analysis, significant improvements in the step rhythm, step shape consistency, and number of weight-bearing steps were observed in robotically trained compared with manually trained or nontrained mice. In contrast, manual training had no effect on stepping performance, yielding no improvement compared with nontrained mice. Daily bolus quipazine treatment acutely improved the step shape consistency and number of steps executed by both robotically trained and nontrained mice, but these improvements did not persist after quipazine was withdrawn. At the dosage used (0.5 mg/kg body weight), quipazine appeared to facilitate, rather than directly generate, stepping, by enabling the spinal cord neural circuitry to process specific patterns of sensory information associated with weight-bearing stepping. Via this mechanism, quipazine treatment enhanced kinematically appropriate robotic training. When administered intermittently during an extended period of robotic training, quipazine revealed training-induced stepping improvements that were masked in the absence of the pharmacological treatment.

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Section: Introductionmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Spinal Cord-Transected Mice Learn to Step in Response to Quipazine Treatment and Robotic Training

Fong¹,

Cai²,

Otoshi³

et al. 2005

J. Neurosci.

131

126

View full text Add to dashboard Cite

show abstract

“…All mice were spinal cord Tx at the low-thoracic level. [16][17][18] In brief, preoperative care included subcutaneous injection of 1 ml lactate-Ringer's solution, an analgesic (0.1 mg/kg buprenorphine) and an antibiotic (5 mg/kg Baytril). A complete transection of the spinal cord was performed intervertebrally using microscissors inserted between the 9th and 10th thoracic vertebrae in mice under complete anesthesia with 2.5% isoflurane.…”

Section: Methodsmentioning

confidence: 99%

Spontaneous recovery of hindlimb movement in completely spinal cord transected mice: a comparison of assessment methods and conditions

et al. 2006

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Study design: To compare results obtained with a variety of locomotor rating scales in Th9/10 spinal cord transected (Tx) mice. Objectives: To assess spontaneous recovery with a variety of rating scales to find the most sensitive methods for assessing recovery levels in Tx mice and differences associated with gender and condition. Setting: Laval University Medical Center, Neuroscience Unit & Laval University, Department of Anatomy and Physiology, Quebec City, Quebec, Canada. Methods: Scales including the Basso, Beattie and Bresnahan (BBB), the Basso Mouse Score (BMS), the Antri, Orsal and Barthe (AOB), the Motor Function Score (MFS) and the Averaged Combined Score (ACOS) were used to assess, in open-field and treadmill conditions, spontaneous locomotor recovery in male and female Tx mice. Results: The ACOS scale revealed a progressive increase of spontaneous recovery during 5-weeks post-Tx. The other methods detected a progressive increase for the first 2-3 weeks postTx without any significant progress in weeks 4 and 5. Generally, scores obtained with each method were nonsignificantly different between males and females or between open-field and treadmill conditions. Conclusion: These results further confirm the existence of a limited but significant increase of locomotor function recovery, occurring without intervention, in Tx animals. Although each method could detect small levels of recovery, the ACOS method was discriminative enough to detect progressive changes up to 5 weeks post-Tx. In conclusion, the ACOS rating scale was the most discriminative method for assessing the spontaneous return of hindlimb movements found in Tx mice, both in open-field and treadmill conditions.

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“…Indeed, administration of agonists selectively binding serotonergic receptors 2A/2C (5-HTR 2A/2C ) was found to acutely induce locomotor-like movements in hindlimbs of adult mice completely transected at the low-thoracic level. 11 This effect was shown to be blocked by selective 5-HT 2 or N-methyl-d-aspartate receptor antagonists suggesting a combined role for these subtypes of serotonergic and glutamatergic receptors in CPG activation. Using other 5-HT receptor agonists, additional experiments have provided evidence of a more specific role for the 5-HTR 2A rather than for the 5-HTR 2C receptors in spinal stepping generation.…”

mentioning

confidence: 99%

“…14,15 In brief, the use of wild-type and mutant paraplegic mouse models may assist scientists in understanding further the complex pathology of SCI. Recent development of less invasive approaches for surgery on mice (ie, with no laminectomy) [11][12][13][14][15][16] and of functional assessment methods adapted for small-size animals 17,18 will undoubtedly further facilitate the use of murine models in SCI research. This relatively new direction in SCI research will hopefully increase the number of significant findings in supporting the development of more effective therapies for SCI patients.…”

mentioning

confidence: 99%

Paraplegic mice are leading to new advances in spinal cord injury research

Guertin

2005

Spinal Cord

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Study design: Experimental laboratory investigations with paraplegic mouse models. Objectives: To review the most recent advances in the field of spinal cord injury research; immune system response, regeneration, and functional recovery. Settings: Laval University and Laval University Medical Center, Quebec, Canada. Methods: Assessment of regenerative processes and locomotor function recovery induced by a variety of treatments and approaches in wild-type and genetically engineered mice with complete or incomplete lesions of the spinal cord. Results: Recent studies have reported a number of significant observations providing additional insight into the role and mechanism of regeneration, immune system response, and functional recovery after spinal cord injury (SCI) using incomplete paraplegic mice with Nogo-A, NgR, EphA4, GFAP/vimentime, LIF, or Fas gene knock-out. A novel antibody called CXCL10 was also recently found to increase tissue sparing and angiogenesis after SCI. In an attempt to explore the possibilities of reactivating spared neurons below the injury level, researchers have found that pharmacological activation of specific subtypes of serotonin receptors (eg, 5-HT1A/2A/7) can sustain the production of basic locomotor-like movements in complete paraplegic mice. Conclusion: The growing availability of genetically engineered and mutant mouse strains along with molecular biology tools has led scientists to increasingly use murine models in SCI research. These new tools and models may assist scientists in understanding further the complex pathological consequences of SCI.

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Role of NMDA receptor activation in serotonin agonist-induced air-stepping in paraplegic mice

Cited by 34 publications

References 28 publications

Spinal Cord-Transected Mice Learn to Step in Response to Quipazine Treatment and Robotic Training

Spinal Cord-Transected Mice Learn to Step in Response to Quipazine Treatment and Robotic Training

Spontaneous recovery of hindlimb movement in completely spinal cord transected mice: a comparison of assessment methods and conditions

Paraplegic mice are leading to new advances in spinal cord injury research

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