Involvement of ryanodine receptors in neurotrophin-induced hippocampal synaptic plasticity and spatial memory formation

Adasme, Tatiana; Haeger, Paola; Paula-Lima, Andrea; Espinoza, Italo; Casas-Alarcón, M. Mercedes; Carrasco, M. Angélica; Hidalgo, Cecilia

doi:10.1073/pnas.1013580108

Cited by 119 publications

(167 citation statements)

References 45 publications

(65 reference statements)

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“…For example, among the cargos that we characterized, the Kif5C cargos PURα (38) and spectrin (39) have essential roles in synapse development; Kif3A cargos SAP97 (40) and RyR2 (41), and Kif5C cargos JIP-3 (42) from the hippocampus and gephyrin (43) from the PFC, are involved in Alzheimer's disease; and abnormal expression of GAP-43 (Kif5C cargo in PFC) is implicated in schizophrenia (44), suggesting the importance of kinesin cargos in psychiatric disorders.…”

Section: Discussionmentioning

confidence: 99%

New approach to capture and characterize synaptic proteome

Liu¹,

Kadakkuzha²,

Pascal³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Little is known regarding the identity of the population of proteins that are transported and localized to synapses. Here we describe a new approach that involves the isolation and systematic proteomic characterization of molecular motor kinesins to identify the populations of proteins transported to synapses. We used this approach to identify and compare proteins transported to synapses by kinesin (Kif) complexes Kif5C and Kif3A in the mouse hippocampus and prefrontal cortex. Approximately 40-50% of the protein cargos identified in our proteomics analysis of kinesin complexes are known synaptic proteins. We also found that the identity of kinesins and where they are expressed determine what proteins they transport. Our results reveal a previously unappreciated role of kinesins in regulating the composition of synaptic proteome.kinesin | protein transport | synapse | proteome | hippocampus

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Section: Discussionmentioning

confidence: 99%

New approach to capture and characterize synaptic proteome

Liu¹,

Kadakkuzha²,

Pascal³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Intracellular Ca 2+ release by RyRs contributes to NMDAR-dependent long-term postsynaptic potentiation (43,44). Importantly, the postsynaptic Ca 2+ release by RyRs was seen only during early development (<P20), and the leaky RyR2 may contribute to establishment of abnormal synaptic strength during this critical period.…”

Section: Rq Mutation Selectively Enhances Excitatory Synaptic Transmimentioning

confidence: 99%

Leaky RyR2 channels unleash a brainstem spreading depolarization mechanism of sudden cardiac death

Aiba

Wehrens

Noebels

2016

Proc. Natl. Acad. Sci. U.S.A.

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Cardiorespiratory failure is the most common cause of sudden unexplained death in epilepsy (SUDEP). Genetic autopsies have detected "leaky" gain-of-function mutations in the ryanodine receptor-2 (RyR2) gene in both SUDEP and sudden cardiac death cases linked to catecholaminergic polymorphic ventricular tachycardia that feature lethal cardiac arrhythmias without structural abnormality. Here we find that a human leaky RyR2 mutation, R176Q (RQ), alters neurotransmitter release probability in mice and significantly lowers the threshold for spreading depolarization (SD) in dorsal medulla, leading to cardiorespiratory collapse. Rare episodes of sinus bradycardia, spontaneous seizure, and sudden death were detected in RQ/+ mutant mice in vivo; however, when provoked, cortical seizures frequently led to apneas, brainstem SD, cardiorespiratory failure, and death. In vitro studies revealed that the RQ mutation selectively strengthened excitatory, but not inhibitory, synapses and facilitated SD in both the neocortex as well as brainstem dorsal medulla autonomic microcircuits. These data link defects in neuronal intracellular calcium homeostasis to the vulnerability of central autonomic brainstem pathways to hypoxic stress and implicate brainstem SD as a previously unrecognized site and mechanism contributing to premature death in individuals with leaky RYR2 mutations.sudden unexpected death in epilepsy | SUDEP | catecholaminergic polymorphic ventricular tachycardia | CPVT | ryanodine receptor U p to 10% of individuals with seizures of unknown cause and without known structural cardiac pathology die of sudden unexpected death in epilepsy (SUDEP), and this morbidity is second only to stroke in the number of life-years lost (1). Despite the high mortality rate, comparable to that of sudden infant death syndrome (SIDS), the exact causes are unclear, and there is no effective prediction or intervention. Cardiorespiratory dysfunction and collapse have been observed following generalized tonicclonic seizures in a small number of monitored cases (2), "near SUDEP" cases (3), and mouse SUDEP models (4-6). Genes linked with the most common cardiac LQT syndromes including LQT1 (KCNQ1), LQT2 (KCNH2/HERG), and LQT3 (SCN5A) are expressed in both the human heart and brain, where mutations in the kinetics of these membrane ion channels prolong depolarization and produce combined seizure, cardiac arrhythmia, and sudden death phenotypes (7,8). Because mutations in these ion channel genes currently explain only a small fraction of SUDEP cases (7), the search for additional genes and mechanisms is a high priority to understand and treat sudden death risk.Along with cardiac arrhythmia, recent findings in voltage-gated ion channelopathy models point to an extracardiac, central autonomic involvement of these genes in the events leading to sudden cardiac death. Spreading depolarization (SD) is a slow propagating wave of cellular depolarization that occurs in human brain and is known to contribute to transient neurological deficits during migraine ...

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“…Modulation of synaptic plasticity is highly controlled by brain-derived neurotropic factor (BDNF) protein binding to specific tropomyosin receptor kinase B (TrkB) Electro-acupuncture ameliorates cognitive impairment via improvement of brain-derived neurotropic factor-mediated hippocampal synaptic plasticity in cerebral ischemia-reperfusion injured rats receptors (11,12). BDNF is a member of the neurotrophin family (13,14), which is known to not only promote the activity of nerve growth, but also to modulate synaptic plasticity (15).…”

Section: Introductionmentioning

confidence: 99%

Electro-acupuncture ameliorates cognitive impairment via improvement of brain-derived neurotropic factor-mediated hippocampal synaptic plasticity in cerebral ischemia-reperfusion injured rats

Lin

et al. 2017

Experimental and Therapeutic Medicine

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Abstract.A previous study by our group found that electro-acupuncture (EA) at the Shenting (DU24) and Baihui (DU20) acupoints ameliorates cognitive impairment in rats with cerebral ischemia-reperfusion (I/R) injury. However, the precise mechanism of action has remained largely unknown. The present study investigated whether brain-derived neurotropic factor (BDNF) mediates hippocampal synaptic plasticity as the underlying mechanism. Rats were randomly divided into three groups: The sham operation control (Sham) group, the focal cerebral ischemia-reperfusion (I/R) group, and the I/R with EA treatment (I/R+EA) group. The I/R+EA group received EA treatment at the Shenting (DU24) and Baihui (DU20) acupoints after the operation. EA treatment was found to ameliorate neurological deficits (P<0.05) and reduce the cerebral infarct volume (P<0.01). In addition, EA improved cognitive function in cerebral I/R-injured rats (P<0.05). Furthermore, EA treatment promoted synaptic plasticity. Simultaneously, EA increased the hippocampal expression of BDNF, its high-affinity tropomyosin receptor kinase B (TrkB) and post-synaptic density protein-95 (PSD-95) in the rats with cerebral I/R injury. Collectively, the findings suggested that BDNF-mediated hippocampal synaptic plasticity may be one mechanism via which EA treatment at the Shenting (DU24) and Baihui (DU20) acupoints improves cognitive function in cerebral I/R injured rats. IntroductionIn 2011, an estimated 795,000 individuals experienced a stroke event in the United States of America (1). Stroke is one of the most common causes of cognitive impairment (2-4). According to different subtypes and diagnostic criteria of stroke, 17-92% of patients present with cognitive impairment 3 months after a stroke (5). Cognitive impairment can cause a variety of symptoms, such as a decline in attention, memory and problem-solving capability (6); therefore, prevention and treatment of stroke with cognitive impairment has become a priority in the global health sector.Acupuncture at the Shenting (DU24) and Baihui (DU20) acupoints has been used in China to treat cognitive impairment for thousands of years. They are located on a branch of the Du Meridian that runs over the head, which are associated with cognitive function in Traditional Chinese Medicine. Previous studies by our group have confirmed the efficacy of electro-acupuncture (EA) on the Shenting (DU24) and Baihui (DU20) acupoints in the rehabilitation of cognitive impairment in experimental settings (7,8).Although the pathogenic mechanisms of post-stoke cognitive impairment are complex, decreased hippocampal synaptic plasticity has been suggested to be one of the key elements (9,10). Modulation of synaptic plasticity is highly controlled by brain-derived neurotropic factor (BDNF) protein binding to specific tropomyosin receptor kinase B (TrkB) Electro-acupuncture ameliorates cognitive impairment via improvement of brain-derived neurotropic factor-mediated hippocampal synaptic plasticity in cerebral ischemia-reperfusion injured rats

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Involvement of ryanodine receptors in neurotrophin-induced hippocampal synaptic plasticity and spatial memory formation

Cited by 119 publications

References 45 publications

New approach to capture and characterize synaptic proteome

New approach to capture and characterize synaptic proteome

Leaky RyR2 channels unleash a brainstem spreading depolarization mechanism of sudden cardiac death

Electro-acupuncture ameliorates cognitive impairment via improvement of brain-derived neurotropic factor-mediated hippocampal synaptic plasticity in cerebral ischemia-reperfusion injured rats

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