Immature developmental pattern of the monosynaptic reflex in isolated spinal cord of glial mutant taiep rats

Fuenzalida, Marco; Roncagliolo, Pablo; Bonansco, Christian; Roncagliolo, Manuel

doi:10.1016/j.devbrainres.2004.08.007

Cited by 8 publications

(4 citation statements)

References 41 publications

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“…Adult taiep rats have a fused MEPs (see Fig 5), which could be due to the demyelination process that impairs the synchronicity of the action potentials. In fact, in the neonatal spinal cord and in the hippocampal in vitro preparations, taiep rats had an asynchronous transmission of the action potentials and in their corresponding postsynaptic currents [35,36]. Importantly, the mean conduction velocity of the pyramidal tract in wildtype rats is 42.9 ± 1.2 m/s, which is similar to previous reports [31,37].…”

Section: Plos Onesupporting

confidence: 86%

4-aminopyridine improves evoked potentials and ambulation in the taiep rat: A model of hypomyelination with atrophy of basal ganglia and cerebellum

Eguibar,

Cortes,

Hernandez

et al. 2024

PLoS ONE

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The taiep rat is a tubulin mutant with an early hypomyelination followed by progressive demyelination of the central nervous system due to a point mutation in the Tubb4a gene. It shows clinical, radiological, and pathological signs like those of the human leukodystrophy hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC). Taiep rats had tremor, ataxia, immobility episodes, epilepsy, and paralysis; the acronym of these signs given the name to this autosomal recessive trait. The aim of this study was to analyze the characteristics of somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) in adult taiep rats and in a patient suffering from H-ABC. Additionally, we evaluated the effects of 4-aminopyridine (4-AP) on sensory responses and locomotion and finally, we compared myelin loss in the spinal cord of adult taiep and wild type (WT) rats using immunostaining. Our results showed delayed SSEPs in the upper and the absence of them in the lower extremities in a human patient. In taiep rats SSEPs had a delayed second negative evoked responses and were more susceptible to delayed responses with iterative stimulation with respect to WT. MEPs were produced by bipolar stimulation of the primary motor cortex generating a direct wave in WT rats followed by several indirect waves, but taiep rats had fused MEPs. Importantly, taiep SSEPs improved after systemic administration of 4-AP, a potassium channel blocker, and this drug induced an increase in the horizontal displacement measured in a novelty-induced locomotor test. In taiep subjects have a significant decrease in the immunostaining of myelin in the anterior and ventral funiculi of the lumbar spinal cord with respect to WT rats. In conclusion, evoked potentials are useful to evaluate myelin alterations in a leukodystrophy, which improved after systemic administration of 4-AP. Our results have a translational value because our findings have implications in future medical trials for H-ABC patients or with other leukodystrophies.

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Section: Plos Onesupporting

confidence: 86%

4-aminopyridine improves evoked potentials and ambulation in the taiep rat: A model of hypomyelination with atrophy of basal ganglia and cerebellum

Eguibar,

Cortes,

Hernandez

et al. 2024

PLoS ONE

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“…These findings, taken together with the sensitivity of these delayed evoked responses to APV and CNQX, in the presence of PTX, suggest that EPSC ASYN are due to the activation of glutamatergic postsynaptic receptors (NMDA and AMPA) by APs‐evoked glutamate release from presynaptic terminals. Second, the EPSC ASYN could originate from asynchronous arrival of APs (Isaacson and Walmsley,1995; Jonas,2000) or an anomalous burst firing discharge of presynaptic fibers (Hu et al,2001), probably resulting from alterations of the conduction properties or abnormal excitability, as described for other CNS fibers of this mutant (Fuenzalida et al,2004; Roncagliolo et al,2006). In either of these alternatives, whenever the number of affected axons is elevated, the fiber volley waveform should display a significant broadening (Andersen et al,1978; Raastad and Shepherd,2003).…”

Section: Discussionmentioning

confidence: 93%

Asynchronic transmission in the CA3–CA1 hippocampal synapses in the neurological mutant taiep rat

Bonansco

Fuenzalida

Olivares

et al. 2006

J of Neuroscience Research

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For the taiep rat, a neurological mutant with severe astrogliosis secondary to demyelination, we have described alterations in spinal cord synaptic transmission. Asynchronous responses result from phasic action potential-derived glutamate release in this mutant. To evaluate whether this anomalous transmission is also produced in other regions of the taiep CNS and whether its nature involves a presynaptic or postsynaptic disruption, we studied the CA3-CA1 hippocampal synapses. Excitatory postsynaptic currents (EPSC) evoked by stimulation of Schaffer collaterals were recorded from CA1 pyramidal cells on picrotoxin-treated slices. Initial fast and time-locked EPSCs were evoked by conventional stimulation in both control and taiep neurons, showing similar latency and amplitude values unimodally distributed. In a high percentage of taiep neurons (47%), the initial EPSC was frequently followed by additional asynchronous synaptic currents (EPSC(ASYN)) with latencies ranging from 10 to 300 msec. As with initial EPSCs, EPSC(ASYN) were action potential dependent, sensitive to tetrodotoxin, and blocked by D-2-amino-5-phosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione. The occurrence probability of these events decayed monoexponentially as a function of poststimulus time. The elevation of extracellular Ca(2+) induced a reduction of amplitudes and a rate increase of EPSC(ASYN), in parallel with a reduction of paired pulse facilitation of initial EPSCs. The presynaptic fiber volley, extracellularly recorded, showed no significant differences between groups, with similar mean values of area and decay time. These findings in hippocampal circuitry suggest that, in taiep, the asynchronous evoked activity represents a rather generalized phenotype of the glutamatergic synapses and that EPSC(ASYN) seems to be determined by presynaptic alterations.

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“…Indeed, patch clamp recordings of auditory afferent axons reveals that the jitter in timing of single action potentials increases in demyelinated Long Evans Shaker rats (Kim, Renden, & von Gersdorff, 2013). Importantly, in vitro spinal cord preparations from neonate taiep rats showed delayed maturation of monosynaptic reflexes, with stronger paired pulse depression and delayed posttetanic recovery supporting that demyelination alters electrophysiological responses in central pathways (Fuenzalida, Roncagliolo, Bonansco, & Roncagliolo, 2004). Similarly, in vitro recordings on CA1 pyramidal cells on neonatal taiep hippocampus showed higher asynchrony of monosynaptic responses induced by electrical stimulation of Schaffer collaterals with respect to those obtained in control Sprague-Dawley rats (Bonansco, Fuenzalida, Olivares, Molina, & Roncagliolo, 2007), supporting early developmental electrophysiological alterations on taiep phenotype.…”

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Juvenile Taiep rats have shorter dendritic trees in the dorsal field of the hippocampus without spatial learning disabilities

Silva-Gómez

Bravo-Duran

Eguibar

et al. 2018

Synapse

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Myelin mutant taiep rats show a progressive demyelination in the central nervous system due to an abnormal accumulation of microtubules in the cytoplasm and the processes on their oligodendrocytes. Demyelination is associated with electrophysiological alterations and the mutant had a progressive astrocytosis. The illness is associated with change in cytokine levels and in the expression of different nitric oxide synthase and concomitantly lipoperoxidation in several areas of the brain. However, until now there has been no detailed anatomical analysis of neurons in this mutant. The aim of this study was to analyze the dendritic morphology in the hippocampus using Golgi-Cox staining and spatial memory through Morris water maze test in young adult (3 months old) taiep rats and compare them with normal Sprague-Dawley. Our results showed that taiep rats have altered dendritic tree morphology in pyramidal neurons in the CA1 field of the hippocampus, but not in the CA3 region. These morphological changes did not produce a concomitant deficit in spatial memory acquisition or recall at this early stage of the disease. Our results suggest that impairment of dendritic morphology in the CA1 field of the hippocampus is a landmark of the pathology of this progressive multiple sclerosis model.

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Immature developmental pattern of the monosynaptic reflex in isolated spinal cord of glial mutant taiep rats

Cited by 8 publications

References 41 publications

4-aminopyridine improves evoked potentials and ambulation in the taiep rat: A model of hypomyelination with atrophy of basal ganglia and cerebellum

4-aminopyridine improves evoked potentials and ambulation in the taiep rat: A model of hypomyelination with atrophy of basal ganglia and cerebellum

Asynchronic transmission in the CA3–CA1 hippocampal synapses in the neurological mutant taiep rat

Juvenile Taiep rats have shorter dendritic trees in the dorsal field of the hippocampus without spatial learning disabilities

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