Microtubule-associated protein 2 (MAP2) associates with the NMDA receptor and is spatially redistributed within rat hippocampal neurons after oxygen-glucose deprivation

Buddle, Michele; Eberhardt, Eric S.; Ciminello, Lauren H.; Levin, Tal; Wing, Richard A.; DiPasquale, Kathleen; Raley‐Susman, Kathleen M.

doi:10.1016/s0006-8993(03)02758-6

Cited by 62 publications

(42 citation statements)

References 58 publications

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“…Interestingly, we had reported previously that implanted MDMs alone resulted in transient deficits in LTP maintenance at day 7, implying that transient MDM secretions occur after the xenograft (Zink et al, 2002;Anderson et al, 2003). MAP-2 is associated closely with the NMDA receptor and normally is highly localized in the pyramidal cell dendrites comprising the CA1 region of the hippocampus (Buddle et al, 2003). Hence staining of normal CA1 dendritic neuropil for MAP-2 exhibits significant protein expression.…”

Section: Discussionmentioning

confidence: 94%

Memantine Protects Hippocampal Neuronal Function in Murine Human Immunodeficiency Virus Type 1 Encephalitis

Anderson¹,

Gendelman²,

Xiong³

2004

J. Neurosci.

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Memantine, a low-to-moderate-affinity NMDA receptor antagonist, can be used to treat cognitive impairment associated with Alzheimer's disease. However, its potential neuroprotective effects for human immunodeficiency virus type 1-associated (HIV-1-associated) dementia are less well appreciated. To this end we studied hippocampal synaptic function in a severe combined immunodeficient (SCID) mouse model of HIV-1 encephalitis (HIVE). Human monocyte-derived macrophages (MDMs) infected with HIV-1 ADA were injected stereotactically into the caudate and putamen of SCID mice, generating HIVE. These brain subregions are among those most affected in humans. Impaired synaptic transmission and long-term potentiation (LTP) were detected in the CA1 region of hippocampal brain slices of HIVE mice. Memantine-treated HIVE mice showed significant improvements in synaptic function during frequency facilitation tests and LTP induced by high-frequency stimulation when compared with untreated animals. Immunocytochemical measures of neuronal antigens mirrored the neuronal physiological tests. These results demonstrate that memantine attenuates hippocampal synaptic impairment in murine HIVE and provide a rationale for its use in infected humans who experience cognitive decline.

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Section: Discussionmentioning

confidence: 94%

Memantine Protects Hippocampal Neuronal Function in Murine Human Immunodeficiency Virus Type 1 Encephalitis

Anderson¹,

Gendelman²,

Xiong³

2004

J. Neurosci.

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“…Mtap2 has a recognized role of scaffolding for the localization of signal transduction apparatus in dendrites, particularly near spines. It binds the actin skeleton and is found in close association with key dendritic proteins, including PKA, tyrosine kinases Src, Grb2, and Fyn (Dehmelt and Halpain, 2005), voltage-dependent calcium channel Cav1.2 (Davare et al, 1999), and NMDA receptors (Husi et al, 2000;Buddle et al, 2003). Mtap2 places TREK-1 at the center of dynamic postsynaptic protein complexes that comprises cytoskeleton elements, ion channels, neurotransmitters receptors, and regulatory proteins.…”

Section: Discussionmentioning

confidence: 99%

“…Neurotrophins such as BDNF prevent destabilization of the microtubule network and favor the microtubule-based transport of NMDA receptors to dendritic membrane (Yuen et al, 2005). It is also known that expression levels and distributions of Mtap2 can be affected by oxygen-glucose deprivation in adult hippocampal slices (Buddle et al, 2003). Therefore, regulation of NMDA receptors and TREK-1 background channels via Mtap2 phosphorylation states or expression levels potentially provides important mechanisms for regulating synaptic plasticity and associated learning and memory.…”

Section: Discussionmentioning

confidence: 99%

Mtap2 Is a Constituent of the Protein Network That Regulates Twik-Related K⁺Channel Expression and Trafficking

Sandoz¹,

Tardy²,

Thümmler³

et al. 2008

J. Neurosci.

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Twik-related Kϩ (TREK) channels produce background currents that regulate cell excitability. In vivo, TREK-1 is involved in neuronal processes including neuroprotection against ischemia, general anesthesia, pain perception, and mood. Recently, we demonstrated that A-kinase anchoring protein AKAP150 binds to a major regulatory domain of TREK-1, promoting drastic changes in channel regulation by polyunsaturated fatty acids, pH, and stretch, and by G-protein-coupled receptors to neurotransmitters and hormones. Here, we show that the microtubule-associated protein Mtap2 is another constituent of native TREK channels in the brain. Mtap2 binding to TREK-1 and TREK-2 does not affect directly channel properties but enhances channel surface expression and current density. This effect relies on Mtap2 binding to microtubules. Mtap2 and AKAP150 interacting sites in TREK-1 are distinct and both proteins can dock simultaneously. Their effects on TREK-1 surface expression and activation are cumulative. In neurons, the three proteins are simultaneously detected in postsynaptic dense bodies. AKAP150 and Mtap2 put TREK channels at the center of a complex protein network that finely tunes channel trafficking, addressing, and regulation.

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“…Calpain-mediated truncation of the L-type calcium channel occurs both in vitro Pettigrew et al (1996), Buddle et al (2003), and Ziemka-Na"ecz et al (2003) Abbreviations: AMPA, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; MAP, microtubule-associated protein; NMDA, N-methyl-D-aspartic acid; PSD, postsynaptic density protein; SAP-97, synapse associated protein-97. (De Jongh et al, 1994) and in hippocampal neurons exposed to NMDA (Hell et al, 1996).…”

Section: Plasma Membrane and Synapsementioning

confidence: 99%

“…Microtubule-associated protein II is susceptible to calpain-mediated cleavage, as in vivo excitotoxicity leads to calpainmediated loss of MAP2 immunoreactivity (Siman and Noszek, 1988). Similar degradation of MAP2 occurs after oxygen-glucose deprivation in hippocampal slice culture (Buddle et al, 2003) and in in vivo focal (Pettigrew et al, 1996) and global ischemia (Ziemka-Na"ecz et al, 2003). This degradation of MAP2 is preceded by calpain activation, and is prevented by calpain inhibition (Inuzuka et al, 1990).…”

Section: Plasma Membrane and Synapsementioning

confidence: 99%

Mechanistic Role of Calpains in Postischemic Neurodegeneration

Bevers

Neumar

2007

J Cereb Blood Flow Metab

137

132

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The calpain family of proteases is causally linked to postischemic neurodegeneration. However, the precise mechanisms by which calpains contribute to postischemic neuronal death have not been fully elucidated. This review outlines the key features of the calpain system, and the evidence for its causal role in postischemic neuronal pathology. Furthermore, the consequences of specific calpain substrate cleavage at various subcellular locations are explored. Calpain substrates within synapses, plasma membrane, endoplasmic reticulum, lysosomes, mitochondria, and the nucleus, as well as the overall effect of postischemic calpain activity on calcium regulation and cell death signaling are considered. Finally, potential pathways for calpain-mediated neurodegeneration are outlined in an effort to guide future studies aimed at understanding the downstream pathology of postischemic calpain activity and identifying optimal therapeutic strategies.

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Microtubule-associated protein 2 (MAP2) associates with the NMDA receptor and is spatially redistributed within rat hippocampal neurons after oxygen-glucose deprivation

Cited by 62 publications

References 58 publications

Memantine Protects Hippocampal Neuronal Function in Murine Human Immunodeficiency Virus Type 1 Encephalitis

Memantine Protects Hippocampal Neuronal Function in Murine Human Immunodeficiency Virus Type 1 Encephalitis

Mtap2 Is a Constituent of the Protein Network That Regulates Twik-Related K⁺Channel Expression and Trafficking

Mechanistic Role of Calpains in Postischemic Neurodegeneration

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Microtubule-associated protein 2 (MAP2) associates with the NMDA receptor and is spatially redistributed within rat hippocampal neurons after oxygen-glucose deprivation

Cited by 62 publications

References 58 publications

Memantine Protects Hippocampal Neuronal Function in Murine Human Immunodeficiency Virus Type 1 Encephalitis

Memantine Protects Hippocampal Neuronal Function in Murine Human Immunodeficiency Virus Type 1 Encephalitis

Mtap2 Is a Constituent of the Protein Network That Regulates Twik-Related K+Channel Expression and Trafficking

Mechanistic Role of Calpains in Postischemic Neurodegeneration

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Product

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Mtap2 Is a Constituent of the Protein Network That Regulates Twik-Related K⁺Channel Expression and Trafficking