Microtubule disruption, not calpain-dependent loss of MAP2, contributes to enduring NMDA-induced dendritic dysfunction in acute hippocampal slices

Hoskison, M.M.; Shuttleworth, C. William

doi:10.1016/j.expneurol.2006.06.010

Cited by 36 publications

(38 citation statements)

References 46 publications

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“…Excessive glutamate receptor stimulation induced by physiological stimulation or exposure of glutamate or agonists of its receptors causes dendritic injury and/or MAP2 loss (Siman and Noszek, 1988;Bigot et al, 1991;Felipo et al, 1993;Arias et al, 1997;Faddis et al, 1997;Steward and Halpain, 1999;Swann et al, 2000;Vaillant et al, 2002). Recent studies in hippocampal slices further demonstrated that these changes are calcium-dependent (Hoskison and Shuttleworth, 2006;Hoskison et al, 2007). Here we demonstrated that loss of excitatory synaptic input, which might be assumed to cause a decrease in [Ca 2+ ] i , also produces MAP2 loss or alternation.…”

Section: Discussionsupporting

confidence: 55%

“…and adult brain. This idea is supported by dynamic regulation of MAP2 expression and its involvement in dynamic changes in neuronal morphology caused by excitotoxins (Siman and Noszek, 1988;Bigot et al, 1991;Felipo et al, 1993;Arias et al, 1997;Faddis et al, 1997;Hoskison and Shuttleworth, 2006;Hoskison et al, 2007), traumatic brain injury (Taft et al, 1992;Folkerts et al, 1998), or focal ischemia (Pettigrew et al, 1996;Schwab et al, 1998). In addition, manipulations of synaptic activity alter the immunoreactivity for MAP2 in dendrites (Hendry and Bhandari, 1992;Steward and Halpain, 1999;Vaillant et al, 2002), further suggesting that synaptic activity either directly or indirectly regulates MAP2 expression.…”

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confidence: 94%

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Rapid regulation of microtubule-associated protein 2 in dendrites of nucleus laminaris of the chick following deprivation of afferent activity

Wang

Rubel

2008

Neuroscience

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Differential innervation of segregated dendritic domains in the chick nucleus laminaris (NL), composed of third-order auditory neurons, provides a unique model to study synaptic regulation of dendritic structure. Altering the synaptic input to one dendritic domain affects the structure and length of the manipulated dendrites while leaving the other set of unmanipulated dendrites largely unchanged. Little is known about the effects of neuronal input on the cytoskeletal structure of NL dendrites and whether changes in the cytoskeleton are responsible for dendritic remodeling following manipulations of synaptic inputs. In this study, we investigate changes in the immunoreactivity of high-molecular weight microtubule associated protein 2 (MAP2) in NL dendrites following two different manipulations of their afferent input. Unilateral cochlea removal eliminates excitatory synaptic input to the ventral dendrites of the contralateral NL and the dorsal dendrites of the ipsilateral NL. This manipulation produced a dramatic decrease in MAP2 immunoreactivity in the deafferented dendrites. This decrease was detected as early as three hours following the surgery, well before any degeneration of afferent axons. A similar decrease in MAP2 immunoreactivity in deafferented NL dendrites was detected following a midline transection that silences the excitatory synaptic input to the ventral dendrites on both sides of the brain. These changes were most distinct in the caudal portion of the nucleus where individual deafferented dendritic branches contained less immunoreactivity than intact dendrites. Our results suggest that the cytoskeletal protein MAP2, which is distributed in dendrites, perikarya, and postsynaptic densities, may play a role in deafferentation-induced dendritic remodeling. Keywordsdeafferentation; dendritic plasticity; afferent regulation; cytoskeleton Microtubules are a major cytoskeletal component of neuronal dendritic structure. It is well established that microtubule associated protein 2 (MAP2) binding increases the stability of the microtubule network and dendritic structure (Serrano et al., 1984;Kowalski and Williams, 1993;Yamauchi et al., 1993;Sánchez et al., 2000;Harada et al., 2002). MAP2 has been proposed to play a fundamental role as a regulator of dendritic morphology in the developing Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. and adult brain. This idea is supported by dynamic regulation of MAP2 expression and its involvement in dynamic changes in neuronal morphology caused by excitotoxins (Siman and Noszek, 1988;Bigot et al., 1991;Felipo et al., 199...

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Section: Discussionsupporting

confidence: 55%

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confidence: 94%

Rapid regulation of microtubule-associated protein 2 in dendrites of nucleus laminaris of the chick following deprivation of afferent activity

Wang

Rubel

2008

Neuroscience

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“…In addition, we have shown recently that treatment of human T cells with the microtubule stabilizer taxol rescues GRK2 ϩ/Ϫ cells from deficient agonist-induced internalization of the ␤-adrenergic receptor . Interestingly, there is evidence that microtubule dissociation precedes MAP2 loss and that the microtubule stabilizer taxol can reduce neuronal damage in a hippocampal slice model of excitotoxic neuronal injury (Hoskison and Shuttleworth, 2006). The consequences of reduced GRK2 for cytoskeletal changes and neuronal damage remain to be determined, but it is conceivable that the earlier loss of the neuronal microtubule-associated protein MAP2 in animals with low GRK2 is caused by direct interactions of GRK2 with cytoskeletal elements.…”

Section: Discussionmentioning

confidence: 99%

Low Endogenous G-Protein-Coupled Receptor Kinase 2 Sensitizes the Immature Brain to Hypoxia–Ischemia-Induced Gray and White Matter Damage

Nijboer¹,

Kavelaars²,

Vroon³

et al. 2008

J. Neurosci.

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Hypoxic-ischemic brain injury is regulated in part by neurotransmitter and chemokine signaling via G-protein-coupled receptors (GPCRs). GPCR-kinase 2 (GRK2) protects these receptors against overstimulation by inducing desensitization. Neonatal hypoxic-ischemic brain damage is preceded by a reduction in cerebral GRK2 expression. We determined the functional importance of GRK2 in hypoxic-ischemic brain damage.Nine-day-old wild-type and GRK2 ϩ/Ϫ mice with a ϳ50% reduction in GRK2 protein were exposed to unilateral carotid artery occlusion and hypoxia. In GRK2 ϩ/Ϫ animals, gray and white matter damage was aggravated at 3 weeks after hypoxia-ischemia. In addition, cerebral neutrophil infiltration was increased in GRK2 ϩ/Ϫ animals. Neutrophil depletion reduced brain damage, but neuronal loss was still more pronounced in GRK2 ϩ/Ϫ animals. Onset of neuronal loss was advanced in GRK2 ϩ/Ϫ animals regardless of neutrophil depletion. White matter injury was advanced in GRK2 ϩ/Ϫ animals and was not affected by neutrophil depletion. Activation/infiltration of microglia/macrophages was stronger in GRK2 ϩ/Ϫ brains but only occurred 24 h after hypoxia-ischemia and is therefore not the primary cause of increased damage. During hypoxia, cerebral blood flow was reduced to the same extent in both genotypes. In vitro, GRK2 ϩ/Ϫ hippocampal slices and cerebellar granular neurons were more sensitive to glutamate-induced death.We propose the novel concept that the kinase GRK2 regulates onset and magnitude of hypoxic-ischemic brain damage. Increased gray and white matter damage in GRK2 ϩ/Ϫ animals was not dependent on infiltrating neutrophils and occurred before microglia/macrophage activation was detected. Collectively, our data suggest that cerebral GRK2 has an important endogenous neuroprotective role in ischemic cerebral damage.

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“…It is not clear how the high dose of manganese (400 mM, 25 mM vitreal concentration) blocks enhancement of the SC, but the following could be conjectured: this dose may be sufficiently toxic to directly reduce the uptake of manganese into the retinal ganglion cell; the influx of manganese may be pharmacologically blocked [in a similar manner to the blockade of the NMDA channels (38)]; or microtubule axonal transport is disrupted by excessive intracellular loading of manganese and subsequent sustained release of intracellular stores of calcium or as a consequence of adverse changes in vitreous pH (pH ¼ 4.75 in the 400 mM solution). Such excessive intracellular calcium loading can lead to breakdown of the microtubule-associated protein, MAP2, by the calcium-dependent protease calpain (39).…”

Section: Discussionmentioning

confidence: 99%

Quantitative manganese tract tracing: dose‐dependent and activity‐independent terminal labelling in the mouse visual system

Lowe¹,

Thompson

Sibson³

2008

NMR in Biomedicine

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At concentrations sufficient for visualisation using MRI, manganese (Mn) is believed to behave as a calcium analogue. This study examines different concentrations of Mn for enhanced MR tract tracing. The premise of activity-dependent axonal transport was also examined by partial or complete blockade of retinal ganglion cell activity. Quantitative T(1) maps and semi-quantitative normalised signal intensities in the superior colliculi facilitated assessment of applied intraocular concentrations and activity dependence, respectively. Varying the concentration of applied Mn revealed a non-monotonic profile, with optimal, unfavourable and undesirable effects noted: 25 mM proved optimal, showing a maximal decrease in T(1), whereas 400 mM was associated with no terminal-field enhancement. The estimated vitreal concentration for optimal transport of Mn (2 mM) is substantially lower than that used in previous studies of the mouse. Both the partial blockade of inputs to 50% of retinal ganglion cells by a mGluR6 glutamate agonist and the complete blockade of all retinal ganglion cell activity with tetrodotoxin failed to decrease the relative enhancement in the superior colliculus. The failure to prevent axonal transport of Mn by blocking activity (and therefore theoretically the intracellular influx) appeared to be paradoxical. The optimal vitreal concentration of Mn has previously been shown to facilitate massive intracellular uptake of Mn, competitively blocking calcium, and 1 mM Mn blocks neurotransmission pre-synaptically. These results suggest that, at concentrations required for optimal Mn-enhanced MRI tract tracing in the visual system of the mouse, the uptake and transport of Mn may be dominated by passive mechanisms, which may also block neurotransmission.

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Microtubule disruption, not calpain-dependent loss of MAP2, contributes to enduring NMDA-induced dendritic dysfunction in acute hippocampal slices

Cited by 36 publications

References 46 publications

Rapid regulation of microtubule-associated protein 2 in dendrites of nucleus laminaris of the chick following deprivation of afferent activity

Rapid regulation of microtubule-associated protein 2 in dendrites of nucleus laminaris of the chick following deprivation of afferent activity

Low Endogenous G-Protein-Coupled Receptor Kinase 2 Sensitizes the Immature Brain to Hypoxia–Ischemia-Induced Gray and White Matter Damage

Quantitative manganese tract tracing: dose‐dependent and activity‐independent terminal labelling in the mouse visual system

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