Increased long-term potentiation in the CA1 region of rat hippocampus via modulation of GTPase signalling or inhibition of Rho kinase

O’Kane, E.M.; Stone, T.W.; Morris, Brian J.

doi:10.1016/j.neuropharm.2003.11.020

Cited by 42 publications

(22 citation statements)

References 40 publications

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“…Therefore, these results suggested that ROCKs are also directly involved in the formation of spines as well as the maintenance of their morphology. In accordance with these morphological studies, the administration of Y-27632 was also shown to enhance the magnitude of LTP in acute hippocampal slices [73], suggesting that ROCK may play an inhibitory role in LTP. However, a recent study using the more specific ROCK inhibitor H-1152 revealed that the presence of this drug reduced the amplitude of potentiation [74].…”

Section: Rocks (Rho-kinases)supporting

confidence: 77%

“…In the search for important administrators of the cytoskeleton, RhoGTPases and their associated protein kinases have emerged as crucial players in spine actin regulation. These GTPases, Manipulations in the Rho-GTPase signaling pathways can lead to a large number of deficits in spine morphology [6][7][8][9], the structural remodeling of neurons [10][11][12], synaptic plasticity [13][14][15], as well as changes in response to specific learning tasks [16][17][18]. Additionally, Rho-associated kinases are involved in both syndromic and non-syndromic mental retardation [19].…”

Section: Introductionmentioning

confidence: 99%

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Distinct Roles of the Rho-GTPase Associated Kinases PAK and ROCK in the Regulation of Dendritic Spines and Synaptic Plasticity

Asrar¹,

Jia²

2014

TONEURJ

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Dendritic spines are highly specialized neuronal structures that are the major postsynaptic sites for excitatory input. These actin-rich expansions are highly versatile in adapting their morphology and density towards the support of synaptic transmission and plasticity. Among the chief factors known to be crucial in the modulation of the actin cytoskeleton, the Rho-GTPases and their associated signaling effectors are particularly important. This signaling system is involved in numerous regulatory processes, including cell morphology, structural dynamics and cell motility. Accordingly, the disruption of Rho-related signaling has a profound effect on the integrity of neurons, resulting in abnormalities with neurite outgrowth, dendritic arborization, spine properties and plasticity. These perturbations can dramatically alter normal synaptic function, including hippocampal long-term potentiation (LTP), resulting in cognitive defects. Additionally, RhoGTPase-associated signaling disorders have also been implicated in numerous forms of mental retardation. Therefore, the elucidation of the underlying mechanisms involved in this pathway and their critical association with dendritic spines remains a major focus of research concerning the cellular basis of cognitive function. Here we will discuss our recent data obtained utilizing knockout animals deficient in the expression of PAKs (p21-activated kinases) and ROCKs (Rhokinases), predominant protein kinases known to be directly activated by the Rho-GTPases. A downstream target for both PAKs and ROCKs, LIMKs (Lin-11, Isl-1, and Mec-3 kinase), will also be discussed. While it is evident that these kinase families all serve towards spine and synaptic regulation, their individual roles in the achievement of this goal may be quite different.

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Section: Rocks (Rho-kinases)supporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Distinct Roles of the Rho-GTPase Associated Kinases PAK and ROCK in the Regulation of Dendritic Spines and Synaptic Plasticity

Asrar¹,

Jia²

2014

TONEURJ

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“…Significant RhoA upregulation (Brabeck et al, 2004) and activation has been reported in both the cortex and hippocampus following traumatic brain injury (Dubreuil et al, 2006). The activation of Rho GTPases occurs during synaptic remodeling, neuronal activity and synaptic plasticity in the central nervous system (Luo, 2002;O'Kane et al, 2004O'Kane et al, , 2003. Since it is widely established that Lingo-1 mediates axonal outgrowth, oligodendrocyte differentiation and axon myelination largely due to its interaction with, and activation of RhoA, it has been hypothesized that Lingo-1 plays a significant inhibitory role in this debilitating neurological disorder.…”

Section: Spinal Cord Injury Traumatic Brain Injury and Multiple Sclementioning

confidence: 99%

A decade from discovery to therapy: Lingo-1, the dark horse in neurological and psychiatric disorders

Andrews

Fernandez

2015

Neuroscience & Biobehavioral Reviews

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Leucine-rich repeat and immunoglobulin domain-containing protein (Lingo-1) is a potent negative regulator of neuron and oligodendrocyte survival, neurite extension, axon regeneration, oligodendrocyte differentiation, axonal myelination and functional recovery; all processes highly implicated in numerous brain-related functions. Although playing a major role in developmental brain functions, the potential application of Lingo-1 as a therapeutic target for the treatment of neurological disorders has so far been underestimated. A number of preclinical studies have shown that various methods of antagonizing Lingo-1 results in neuronal and oligodendroglial survival, axonal growth and remyelination; however to date literature has only detailed applications of Lingo-1 targeted therapeutics with a focus primarily on myelination disorders such as multiple sclerosis and spinal cord injury; omitting important information regarding Lingo-1 signaling cofactors. Here, we provide for the first time a complete and thorough review of the implications of Lingo-1 signaling in a wide range of neurological and psychiatric disorders, and critically examine its potential as a novel therapeutic target for these disorders. Disciplines Medicine and Health Sciences | Social and Behavioral Sciences AbstractLeucine-rich repeat and immunoglobulin domain-containing protein (Lingo-1) is a potent negative regulator of neuron and oligodendrocyte survival, neurite extension, axon regeneration, oligodendrocyte differentiation, axonal myelination and functional recovery; all processes highly implicated in numerous brain-related functions. Although playing a major role in developmental brain functions, the potential application of Lingo-1 as a therapeutic target for the treatment of neurological disorders has so far been under-estimated. A number of preclinical studies have shown that various methods of antagonizing Lingo-1 results in neuronal and oligodendroglial survival, axonal growth and remyelination; however to date literature has only detailed applications of Lingo-1 targeted therapeutics with a focus primarily on myelination disorders such as multiple sclerosis and spinal cord injury; omitting important information regarding Lingo-1 signaling co-factors. Here, we provide for the first time a complete and thorough review of the implications of Lingo-1 signaling in a wide range of neurological and psychiatric disorders, and critically examine its potential as a novel therapeutic target for these disorders.

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“…ROCK, which is involved in some functions of the central nervous system, regulates axon outgrowth and growth cone dynamics (Arimura et al, 2000;Bito et al, 2000). It is involved in ischemic brain damage (Toshima et al, 2000), and it plays a role in long-term potentiation in CA1 region of hippocampus (ÓKane et al, 2004), and long-term spatial memory (Dash et al, 2004).…”

Section: Consequently Sh-sy5y Cells May Fulfill the Definitions Of Nmentioning

confidence: 99%

ROCK2 regulates bFGF-induced proliferation of SH-SY5Y cells through GSK-3β and β-catenin pathway

Boku¹,

Nakagawa²,

Toda³

et al. 2013

Brain Research

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Increased neurogenesis by promoting proliferation of neural precursor cells in the adult dentate gyrus might be beneficial for the treatment of psychiatric disorders. Results demonstrate that bFGF is necessary for the proliferation of neural precursor cells and that the glycogen synthase kinase-3β (GSK-3β) and β-catenin pathway plays a role in it. However, the detailed mechanism of proliferation of neural precursor cells remains unclear. To elucidate that mechanism, we investigated the role of Rho-associated coiled-coil kinase (ROCK) in bFGF-induced proliferation using SH-SY5Y cells as a model of neural precursor-like cells. Y27632, a specific inhibitor of ROCK, decreased bFGF-induced proliferation. Lithium (Li), an inhibitor of GSK-3β, recovered Y27632-decreased proliferation and quercetin (Que), an inhibitor of β-catenin pathway, reversed the recovery effect of Li. Both nuclear β-catenin and cyclin D1 expression were altered by bFGF, Y27632, Li, and Que in parallel with the case of proliferation. Furthermore, bFGF inactivated GSK-3β through increasing the phosphorylation of Ser 9 on GSK-3β, which is reversed by Y27632 through increased phosphorylation of Tyr 216 on GSK-3β. ROCK has two subtypes: ROCK1 and ROCK2. Investigation with siRNA for ROCKs showed that ROCK2 is involved in bFGF-induced proliferation, but not ROCK1. These results suggest that ROCK2 might mediate bFGF-induced proliferation of SH-SY5Y cells through GSK-3β and β-catenin pathway. Further investigation of detailed mechanisms regulating the ROCK2/GSK-3β/β-catenin pathway might engender the development of new therapeutic targets of psychiatric disorders.

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Increased long-term potentiation in the CA1 region of rat hippocampus via modulation of GTPase signalling or inhibition of Rho kinase

Cited by 42 publications

References 40 publications

Distinct Roles of the Rho-GTPase Associated Kinases PAK and ROCK in the Regulation of Dendritic Spines and Synaptic Plasticity

Distinct Roles of the Rho-GTPase Associated Kinases PAK and ROCK in the Regulation of Dendritic Spines and Synaptic Plasticity

A decade from discovery to therapy: Lingo-1, the dark horse in neurological and psychiatric disorders

ROCK2 regulates bFGF-induced proliferation of SH-SY5Y cells through GSK-3β and β-catenin pathway

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