Age‐related changes in hippocampal‐dependent synaptic plasticity and memory mediated by p75 neurotrophin receptor

: Neurological diseases bring great mental and physical torture to the patients, and have long-term and sustained negative effects on families and society. The attention to neurological diseases is increasing, and the improvement of the material level is accompanied by an increase in the demand for mental level. The p75 neurotrophin receptor (p75NTR) is a low-affinity neurotrophin receptor and involved in diverse and pleiotropic effects in the developmental and adult central nervous system (CNS). Since neurological diseases are usually accompanied by the regression of memory, the pathogenesis of p75NTR also activates and inhibits other signaling pathways, which has a serious impact on the learning and memory of patients. The results of studies shown that p75NTR is associated with LTP/LTD-induced synaptic enhancement and inhibition, suggest that p75NTR may be involved in the progression of synaptic plasticity. And its pro-apoptotic effect is associated with activation of proBDNF and inhibition of proNGF, and TrkA/p75NTR imbalance leads to pro-survival or pro-apoptotic phenomena. It can be inferred that p75NTR mediates apoptosis in the hippocampus and amygdale, which may affect learning and memory behavior. This article mainly discusses the relationship between p75NTR and learning memory and associated mechanisms, which may provide some new ideas for the treatment of neurological diseases.

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17β-estradiol modifies stress-induced and age-related changes in hippocampal synaptic plasticity.

Behavioral Neuroscience ◽

10.1037/0735-7044.122.2.301 ◽

2008 ◽

Vol 122 (2) ◽

pp. 301-309 ◽

Cited By ~ 30

Author(s):

Michael R. Foy ◽

Michel Baudry ◽

Judith G. Foy ◽

Richard F. Thompson

Keyword(s):

Synaptic Plasticity ◽

Hippocampal Synaptic Plasticity ◽

Age Related ◽

17Β Estradiol ◽

Age Related Changes

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The role of brain-derived neurotrophic factor and the neurotrophin receptor p75NTR in age-related brain atrophy and the transition to Alzheimer’s disease

Reviews in the Neurosciences ◽

10.1515/revneuro-2021-0111 ◽

2022 ◽

Vol 0 (0) ◽

Author(s):

Shaun Cade ◽

Xin-Fu Zhou ◽

Larisa Bobrovskaya

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Synaptic Plasticity ◽

Neurotrophic Factor ◽

Molecular Mechanisms ◽

Brain Derived Neurotrophic Factor ◽

Neurotrophin Receptor ◽

Current Evidence ◽

Synaptic Dysfunction ◽

Age Related

Abstract Alzheimer’s disease is a neurodegenerative condition that is potentially mediated by synaptic dysfunction before the onset of cognitive impairments. The disease mostly affects elderly people and there is currently no therapeutic which halts its progression. One therapeutic strategy for Alzheimer’s disease is to regenerate lost synapses by targeting mechanisms involved in synaptic plasticity. This strategy has led to promising drug candidates in clinical trials, but further progress needs to be made. An unresolved problem of Alzheimer’s disease is to identify the molecular mechanisms that render the aged brain susceptible to synaptic dysfunction. Understanding this susceptibility may identify drug targets which could halt, or even reverse, the disease’s progression. Brain derived neurotrophic factor is a neurotrophin expressed in the brain previously implicated in Alzheimer’s disease due to its involvement in synaptic plasticity. Low levels of the protein increase susceptibility to the disease and post-mortem studies consistently show reductions in its expression. A desirable therapeutic approach for Alzheimer’s disease is to stimulate the expression of brain derived neurotrophic factor and potentially regenerate lost synapses. However, synthesis and secretion of the protein are regulated by complex activity-dependent mechanisms within neurons, which makes this approach challenging. Moreover, the protein is synthesised as a precursor which exerts the opposite effect of its mature form through the neurotrophin receptor p75NTR. This review will evaluate current evidence on how age-related alterations in the synthesis, processing and signalling of brain derived neurotrophic factor may increase the risk of Alzheimer’s disease.

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Age-related changes in the synaptic plasticity of rat superior cervical ganglia

Brain Research ◽

10.1016/0006-8993(91)91586-p ◽

1991 ◽

Vol 542 (2) ◽

pp. 324-329 ◽

Cited By ~ 10

Author(s):

Ruilin Wu ◽

David G. McKenna ◽

Donald A. McAfee

Keyword(s):

Synaptic Plasticity ◽

Superior Cervical Ganglia ◽

Age Related ◽

Cervical Ganglia ◽

Age Related Changes

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Sex- and Age-Related P75 Neurotrophin Receptor Expression in the Human Supraoptic Nucleus

Neuroendocrinology ◽

10.1159/000054542 ◽

2000 ◽

Vol 71 (4) ◽

pp. 243-251 ◽

Cited By ~ 9

Author(s):

Tatjana A. Ishunina ◽

Ahmad Salehi ◽

Dick F. Swaab

Keyword(s):

Supraoptic Nucleus ◽

Receptor Expression ◽

Neurotrophin Receptor ◽

P75 Neurotrophin Receptor ◽

Age Related

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Age-Related Changes in Synaptic Plasticity Associated with Mossy Fiber Terminal Integration during Adult Neurogenesis

eNeuro ◽

10.1523/eneuro.0030-20.2020 ◽

2020 ◽

Vol 7 (3) ◽

pp. ENEURO.0030-20.2020 ◽

Cited By ~ 1

Author(s):

Karl D. Murray ◽

Xiao-Bo Liu ◽

Anna N. King ◽

Julie D. Luu ◽

Hwai-Jong Cheng

Keyword(s):

Synaptic Plasticity ◽

Adult Neurogenesis ◽

Mossy Fiber ◽

Age Related ◽

Age Related Changes

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Long-term depression at hippocampal mossy fiber-CA3 synapses involves BDNF but is not mediated by p75NTR signaling

Scientific Reports ◽

10.1038/s41598-021-87769-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Machhindra Garad ◽

Elke Edelmann ◽

Volkmar Leßmann

Keyword(s):

Synaptic Plasticity ◽

Mossy Fiber ◽

Plasminogen Activator Inhibitor ◽

Long Term Potentiation ◽

Neurotrophin Receptor ◽

P75 Neurotrophin Receptor ◽

Plasminogen Activator Inhibitor 1 ◽

Long Term Depression ◽

Ca3 Neurons

AbstractBDNF plays a crucial role in the regulation of synaptic plasticity. It is synthesized as a precursor (proBDNF) that can be proteolytically cleaved to mature BDNF (mBDNF). Previous studies revealed a bidirectional mode of BDNF actions, where long-term potentiation (LTP) was mediated by mBDNF through tropomyosin related kinase (Trk) B receptors whereas long-term depression (LTD) depended on proBDNF/p75 neurotrophin receptor (p75NTR) signaling. While most experimental evidence for this BDNF dependence of synaptic plasticity in the hippocampus was derived from Schaffer collateral (SC)-CA1 synapses, much less is known about the mechanisms of synaptic plasticity, in particular LTD, at hippocampal mossy fiber (MF) synapses onto CA3 neurons. Since proBDNF and mBDNF are expressed most abundantly at MF-CA3 synapses in the rodent brain and we had shown previously that MF-LTP depends on mBDNF/TrkB signaling, we now explored the role of proBDNF/p75NTR signaling in MF-LTD. Our results show that neither acute nor chronic inhibition of p75NTR signaling impairs MF-LTD, while short-term plasticity, in particular paired-pulse facilitation, at MF-CA3 synapses is affected by a lack of functional p75NTR signaling. Furthermore, MF-CA3 synapses showed normal LTD upon acute inhibition of TrkB receptor signaling. Nonetheless, acute inhibition of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of both intracellular and extracellular proBDNF cleavage, impaired MF-LTD. This seems to indicate that LTD at MF-CA3 synapses involves BDNF, however, MF-LTD does not depend on p75NTRs. Altogether, our experiments demonstrate that p75NTR signaling is not warranted for all glutamatergic synapses but rather needs to be checked separately for every synaptic connection.

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Effects of Gestational Inflammation with Postpartum Enriched Environment on Age-Related Changes in Cognition and Hippocampal Synaptic Plasticity-Related Proteins

Neural Plasticity ◽

10.1155/2020/9082945 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Shi-Yu Sun ◽

Xue-Yan Li ◽

He-Hua Ge ◽

Yu-Xin Zhang ◽

Zhe-Zhe Zhang ◽

...

Keyword(s):

Cognitive Impairment ◽

Synaptic Plasticity ◽

Learning And Memory ◽

Spatial Learning ◽

Enriched Environment ◽

Synaptic Proteins ◽

Spatial Learning And Memory ◽

Age Related ◽

Related Proteins ◽

Age Related Changes

Increasing evidence indicates that exposure to inflammation during pregnancy intensifies the offspring’s cognitive impairment during aging, which might be correlated with changes in some synaptic plasticity-related proteins. In addition, an enriched environment (EE) can significantly exert a beneficial impact on cognition and synaptic plasticity. However, it is unclear whether gestational inflammation combined with postnatal EE affects the changes in cognition and synaptic plasticity-related proteins during aging. In this study, pregnant mice were intraperitoneally injected with lipopolysaccharides (LPS, 50 μg/kg) or normal saline at days 15–17 of pregnancy. At 21 days after delivery, some LPS-treated mice were randomly selected for EE treatment. At the age of 6 and 18 months, Morris water maze (MWM) and western blotting were, respectively, used to evaluate or measure the ability of spatial learning and memory and the levels of postsynaptic plasticity-related proteins in the hippocampus, including postsynaptic density protein 95 (PSD-95), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) GluA1 subunit, and Homer-1b/c. The results showed that 18-month-old control mice had worse spatial learning and memory and lower levels of these synaptic plasticity-related proteins (PSD-95, GluA1, and Homer-1b/c) than the 6-month-old controls. Gestational LPS exposure exacerbated these age-related changes of cognition and synaptic proteins, but EE could alleviate the treatment effect of LPS. In addition, the performance during learning and memory periods in the MWM correlated with the hippocampal levels of PSD-95, GluA1, and Homer-1b/c. Our results suggested that gestational inflammation accelerated age-related cognitive impairment and the decline of PSD-95, GluA1, and Homer-1b/c protein expression, and postpartum EE could alleviate these changes.

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