Is Purkinje cell loss in Leigh's disease an excitotoxic event secondary to damage to inferior olivary nuclei?*

Jb, Cavanagh

doi:10.1111/j.1365-2990.1994.tb01014.x

Cited by 11 publications

(5 citation statements)

References 30 publications

(10 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The excitatory inputs to the Purkinje cells are provided by the climbing fibers and parallel fibers through excitatory amino acid receptors (Ross et al, 1990). The neurotransmitters are thought to be aspartate for climbing fibers (Cavanagh, 1994) and glutamate for parallel fibers (Olson et al, 1987). The climbing fibers originate from the contralateral inferior olivary nuclear complex.…”

Section: Purkinje Cell Death: Putative Mechanisms Of Injurymentioning

confidence: 99%

“…Each Purkinje cell throughout the cerebellar cortex directly receives the input from only one climbing fiber (Burt, 1993). Since each climbing fiber may have up to 500 individual synapses on the Purkinje cell, excitation of the climbing fiber may result in a massive, synchronous release of an excitotoxin, such as aspartate (Burt, 1993;Cavanagh, 1994) leading to cell death. A precise topographic relation exists between parts of the inferior olivary nuclear complex and the cerebellar cortical area of termination of these olivocerebellar climbing fibers.…”

Section: Purkinje Cell Death: Putative Mechanisms Of Injurymentioning

confidence: 99%

See 1 more Smart Citation

Purkinje Cell Vulnerability to Mild Traumatic Brain Injury

Fukuda

Aihara

Sagar

et al. 1996

Journal of Neurotrauma

View full text Add to dashboard Cite

In this study we examined the cerebellar response to mild traumatic brain injury by assessing microglial activation and Purkinje cell loss. Activated microglia were identified using the antibodies OX-42 and ED-1 as well as isolectin B4. The anti-Purkinje cell antibody PEP-19 was used to evaluate Purkinje cell loss after injury. The mechanism of cell injury was examined using a monoclonal antibody to the inducible 72-kDa heat shock protein. A monoclonal antibody to the N-terminal sequence of Fos was used as a marker for neuronal activation. There was progressive activation of microglia in the cerebellar vermis within a few days after forebrain injury. In coronal sections the processes of activated microglia were oriented in "stripes" perpendicular to the cortical surface. In sagittal sections the activated microglia were in irregularly shaped clusters or in a fan-like distribution that radiated from the Purkinje cell layer toward the cortical surface. There was a significant loss of Purkinje cells 7 days postinjury as compared to the control group. There was no evidence of induction of heat shock protein in the cerebellum. In addition, there was no evidence of induction of c-Fos protein in either the cerebellar cortex or inferior olivary nuclei within the first 3 h after injury. These studies demonstrate that a fluid percussive impact to the forebrain results in cerebellar damage. The close anatomical association between activated microglia and Purkinje cells suggests that Purkinje cell injury is the cause of the microglial activation. The mechanism of Purkinje cell death, however, remains unclear.

show abstract

Section: Purkinje Cell Death: Putative Mechanisms Of Injurymentioning

confidence: 99%

Section: Purkinje Cell Death: Putative Mechanisms Of Injurymentioning

confidence: 99%

Purkinje Cell Vulnerability to Mild Traumatic Brain Injury

Fukuda

Aihara

Sagar

et al. 1996

Journal of Neurotrauma

View full text Add to dashboard Cite

show abstract

“…In SCA-6, degeneration in precerebellar regions occurs (the vestibular complex, motor cortex, and inferior olive; Ishikawa and others 1999). Detailed analysis of cerebellar disease may implicate the inferior olive in other cases, such as in Leigh’s disease (Cavanagh 1994) or in other forms of SCA (Koeppen 2005). …”

Section: Physiology Of Uvula-nodulusmentioning

confidence: 99%

Topsy Turvy: Functions of Climbing and Mossy Fibers in the Vestibulo-Cerebellum

Barmack

Yakhnitsa

2011

Neuroscientist

View full text Add to dashboard Cite

The cerebellum’s role in sensory-motor control and adaptation is undisputed. However, a key hypothesis pertaining to the function of cerebellar circuitry lacks experimental support. It is universally assumed that the discharge of mossy fibers accounts for modulation of Purkinje cell “simple spikes” (SSs). This assumption acts as a prism through which all other functions of cerebellar circuitry are viewed. The vestibulo-cerebellum (nodulus and uvula) receives a large, unilateral, vestibular primary afferent mossy fiber projection. We can test its role in modulating Purkinje cell SSs by recording the modulated activity of both mossy fiber terminals and Purkinje cell SSs evoked by identical natural vestibular stimulation. Sinusoidal rotation about the longitudinal axis (roll) modulates the activity of vestibular primary afferent mossy and climbing fibers as well as Purkinje cell SSs and complex spikes (CSs). Remarkably, vestibular primary afferent mossy fibers discharge 180 degrees out of phase with SSs. This indicates that mossy fibers cannot account for SS modulation unless an inhibitory synapse is interposed between mossy fibers or vestibular climbing fibers and Purkinje cells. The authors review several experiments that address the relative contributions of mossy and climbing fiber afferents to the modulation of SSs. They conclude that climbing fibers, not mossy fibers, are primarily responsible for the modulation of SSs as well as CSs and they propose revised functions for these two afferent systems.

show abstract

“…In SCA-6, degeneration in pre-cerebellar regions also occurs (the vestibular complex, motor cortex, and inferior olive) (Ishikawa et al 1999;Watase et al 2008). Detailed analysis of cerebellar disease may implicate the inferior olive in other cases, such as in Leigh's disease (Cavanagh 1994) or in other forms of SCA (Koeppen 2005).…”

Section: Abnormal Cerebellar Functionmentioning

confidence: 99%

Vestibulocerebellar Functional Connections

Barmack

Yakhnitsa

2021

Handbook of the Cerebellum and Cerebellar Disorders

View full text Add to dashboard Cite

β-nucleus • CAG repeat disease • Cerebellum • Climbing fiber • Complex spike (CS) • Dorsomedial cell column (DMCC) • Descending vestibular nucleus (DVN) • Lateral reticular nucleus (LRN) • Lateral vestibular nucleus (LVN) • Mossy fiber • Medial vestibular nucleus (MVN) • Nodulus • Optokinetic • Otoliths • Parallel fiber • Parasolitary nucleus (Psol) • semicircular canals • Serotonin 5-HT1A receptor • Simple spike (SS) • Spinocerebellar ataxia (SCA) • Purkinje cells • Superior vestibular nucleus • (SVN) • Vestibular nucleus • Primary afferent • Vestibular system • Y-Group

show abstract

Is Purkinje cell loss in Leigh's disease an excitotoxic event secondary to damage to inferior olivary nuclei?*

Cited by 11 publications

References 30 publications

Purkinje Cell Vulnerability to Mild Traumatic Brain Injury

Purkinje Cell Vulnerability to Mild Traumatic Brain Injury

Topsy Turvy: Functions of Climbing and Mossy Fibers in the Vestibulo-Cerebellum

Vestibulocerebellar Functional Connections

Contact Info

Product

Resources

About