NGF Is Essential for Hippocampal Plasticity and Learning

Conner, J. M.; Franks, Kevin M.; Titterness, Andrea K.; Russell, Kyle; Merrill, David A.; Christie, Brian R.; Sejnowski, Terrence J.; Tuszynski, Mark H.

doi:10.1523/jneurosci.2594-09.2009

Cited by 175 publications

(129 citation statements)

References 59 publications

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“…These are new and compelling data, because learning and memory had not been studied previously. However, endogenous wild-type NGF is known to be essential for the maintenance of adult cholinergic neuronal phenotype (Debeir et al, 1999;Capsoni et al, 2010) and for hippocampal plasticity (Conner et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Ligand-Dependent TrkA Activity in Brain Differentially Affects Spatial Learning and Long-Term Memory

Aboulkassim

Tong²,

Tse³

et al. 2011

Mol Pharmacol

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In the central nervous system, the nerve growth factor (NGF) receptor TrkA is expressed primarily in cholinergic neurons that are implicated in spatial learning and memory, whereas the NGF receptor p75NTR is expressed in many neuronal populations and glia. We asked whether selective TrkA activation may have a different impact on learning, short-term memory, and long-term memory. We also asked whether TrkA activation might affect cognition differently in wild-type mice versus mice with cognitive deficits due to transgenic overexpression of mutant amyloid-precursor protein (APP mice). Mice were treated with wild-type NGF (a ligand of TrkA and p75 NTR ) or with selective pharmacological agonists of TrkA that do not bind to p75NTR . In APP mice, the selective TrkA agonists significantly improved learning and short-term memory. These improvements are associated with a reduction of soluble A␤ levels in the cortex and AKT activation in the cortex and hippocampus. However, this improved phenotype did not translate into improved long-term memory. In normal wild-type mice, none of the treatments affected learning or short-term memory, but a TrkA-selective agonist caused persistent deficits in long-term memory. The deficit in wild-type mice was associated temporally, in the hippocampus, with increased AKT activity, increased brain-derived neurotrophic factor precursor, increased neurotrophin receptor homolog-2 (p75-related protein), and long-term depression. Together, these data indicate that selective TrkA activation affects cognition but does so differently in impaired APP mice versus normal wild-type mice. Understanding mechanisms that govern learning and memory is important for better treatment of cognitive disorders.

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Section: Discussionmentioning

confidence: 99%

Ligand-Dependent TrkA Activity in Brain Differentially Affects Spatial Learning and Long-Term Memory

Aboulkassim

Tong²,

Tse³

et al. 2011

Mol Pharmacol

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“…In addition, the blockage of endogenous NGF also interferes with the rat visual system maturation by influencing the critical period Domenici et al, 1994) and exogenous NGF supply favors longterm depression (LTD) over LTP in visual cortical layer II-III of 16 to 18-day-old rats (Pesavento et al, 2000;Brancucci et al, 2004). NGF has been also reported to play a physiological role in synaptic plasticity in neocortical and hippocampal learning/memory processes (Bonhoeffer et al, 1996;Conner et al, 2009). Degeneration of NGF-dependent basal forebrain cholinergic neurons (BFCNs) characterizes the AD pathology.…”

Section: Ngf Bdnf and Synaptic Plasticitymentioning

confidence: 99%

“…A synaptic-failure is presently considered at the origin of this disorder since the synaptic dysfunction/loss in selected brain area, devoted to memory and learning, appears as the earliest sign of cognitive impairment (Coleman and Yao, 2003;Jacobsen et al, 2006;Pomponi et al, 2008). Recently, an essential role of NGF in intact adult brain has been elegantly proven (Conner et al, 2009). NGF augmentation or blockage in rat cholinergic septo-hippocampal system respectively facilitates or inhibits the electrophysiological LTP induction and the spatial Morris water maze behavioral performance in infused animals.…”

Section: Ngf Bdnf and Synaptic Plasticitymentioning

confidence: 99%

“…NGF augmentation or blockage in rat cholinergic septo-hippocampal system respectively facilitates or inhibits the electrophysiological LTP induction and the spatial Morris water maze behavioral performance in infused animals. In contrast to acute, direct and local BDNF action, the NGF retrograde transport, from the sites of synthesis in hippocampus to projecting cholinergic neurons of the basal forebrain, can modulate cholinergic tone, probably by gene expression stimulation, within its innervation targets and thereby indirectly control neuronal plasticity, learning and memory retention (Conner et al, 2009).…”

Section: Ngf Bdnf and Synaptic Plasticitymentioning

confidence: 99%

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Nerve growth factor as a paradigm of neurotrophins related to Alzheimer's disease

Calissano

Matrone

Amadoro

2010

Developmental Neurobiology

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Converging lines of evidence on the possible connection between NGF signaling and Alzheimer's diseases (AD) are unraveling new facets which could depict this neurotrophin (NTF) in a more central role. AD animal models have provided evidence that a shortage of NGF supply may induce an AD-like syndrome. In vitro experiments, moreover, are delineating a possible temporal and causal link between APP amiloydogenic processing and altered post-translational tau modifications. After NGF signaling interruption, the pivotal upstream players of the amyloid cascade (APP, b-secretase, and active form of c-secretase) are up-regulated, leading to an increased production of amyloid b peptide (Ab) and to its intracellular aggregation in molecular species of different sizes. Contextually, the Ab released pool generates an autocrine toxic loop in the same healthy neurons. At the same time tau protein undergoes anomalous, GSKb-mediated, phosphorylation at specific pathogenetic sites (Ser262 and Thr 231), caspase(s) and calpain-I-mediated truncation, detachment from microtubules with consequent cytoskeleton collapse and axonal transport impairment. All these events are inhibited when the amyloidogenic processing is reduced by b and c secretase inhibitors or anti-Ab antibodies and appear to be causally correlated to TrkA, p75CTF, Ab, and PS1 molecular association in an Ab-mediated fashion. In this scenario, the so-called trophic action exerted by NGF (and possibly also by other neurotrophins) in these targets neurons is actually the result of an anti-amyloidogenic activity. '

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“…NGF can stimulate the differentiation, maintenance, survival and plasticity of neurons, and deficiency of NGF induces apoptosis of neurons 34 . In addition, augmentation of NGF enhances cholinergic neuronal markers and blockade of endogenous NGF impairs the retention of the spatial memory 35 . Administration of NGF is a significant determinant for the recovery of neural behavior 36 .…”

Section: ■ Discussionmentioning

confidence: 99%

Effects of hyperbaric oxygen and nerve growth factor on the long-term neural behavior of neonatal rats with hypoxic ischemic brain damage

et al. 2017

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Effects of hyperbaric oxygen and nerve growth factor on the long-term neural behavior of neonatal rats with hypoxic ischemic brain damage 1Acta Cir. Bras. 2017;32(4):270-279 Abstract Purpose: To evaluate the effects of HBO (Hyperbaric oxygen) and NGF (Nerve growth factor) on the long-term neural behavior of neonatal rats with HIBD (Neonatal hypoxic ischemic brain damage). Methods:The HIBD model was produced by ligating the right common carotid artery of 7 days old SD (Sprague-Dawley) rats followed by 8% O2 + 92% N2 for 2h. Totally 40 rats were randomly divided into 5 groups including sham-operated group, HIBD control group, HBO treated group, NGF treated group and NGF + HBO treated group. The learning and memory ability of these rats was evaluated by Morris water maze at 30 days after birth, and sensory motor function was assessed by experiments of foot error and limb placement at 42 days after birth. Results:The escape latency of HBO treated group, NGF treated group and NGF + HBO treated group was shorter than that of HIBD control group (p<0.01) and longer than that of shamoperated group. The piercing indexes of 3 treated groups were higher than that of HIBD control group (p<0.01). Conclusion: Hyperbaric oxygen and nerve growth factor treatments may improve learning and memory ability and sensory motor function in neonatal rats after hypoxic ischemic brain damage. Key words: Hyperbaric Oxygenation. Nerve Growth Factor. Hypoxia-Ischemia, Brain. Rats. 2-Experimental Surgery 270Effects of hyperbaric oxygen and nerve growth factor on the long-term neural behavior of neonatal rats with hypoxic ischemic brain damage Wei L et. al. Acta Cir Bras. 2017;32(4):270-279 271 researchers have been performed about the roles of HBO and NGF in several aspects, but the effects of HBO and NGF on long-term neural behavior of neonatal rats have not been clearly explained.In the present study, we used SD (Sprague-Dawley) newborn rats to construct HIBD models. Furthermore, the experiments of place navigation, space search, feet errors and limb placement were made to explore learning and memory ability, and sensory motor function in neonatal rats after HIBD. We aimed to study the effects of HBO and NGF on the long-term neural behavior of neonatal rats with HIBD. ■ Methods Preparation of HIBD modelsAll procedures conform to the Principles of Laboratory Animal Care issued by the National Institues of Health, with local laws and regulations, and were approved by the local Animal Care and Use Committee.A total of 40 SD newborn rats of both sexes, weighing 14.5 ± 3.2g, aged 7 days old were selected and purchased from Medical Experimental Animal Center of Guangdong Province. The preparation process of HIBD models was followed as previously described 21 . SD rats were fixed in supine position, and routine disinfection of neck was performed. Subsequently, a 3 mm longitudinal incision was made, and the right common carotid artery was isolated by vessel forceps. The carotid artery was ligated by 0 sterile line, and then the incision was ...

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NGF Is Essential for Hippocampal Plasticity and Learning

Cited by 175 publications

References 59 publications

Ligand-Dependent TrkA Activity in Brain Differentially Affects Spatial Learning and Long-Term Memory

Ligand-Dependent TrkA Activity in Brain Differentially Affects Spatial Learning and Long-Term Memory

Nerve growth factor as a paradigm of neurotrophins related to Alzheimer's disease

Effects of hyperbaric oxygen and nerve growth factor on the long-term neural behavior of neonatal rats with hypoxic ischemic brain damage

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