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brain memory neurotrophins and receptors

Margaret Fahnestock, Arman Shekari
Profound and early basal forebrain cholinergic neuron (BFCN) degeneration is a hallmark of Alzheimer's disease (AD). Loss of synapses between basal forebrain and hippocampal and cortical target tissue correlates highly with the degree of dementia and is thought to be a major contributor to memory loss. BFCNs depend for their survival, connectivity and function on the neurotrophin nerve growth factor (NGF) which is retrogradely transported from its sites of synthesis in the cortex and hippocampus. The form of NGF found in human brain is proNGF...
2019: Frontiers in Neuroscience
Jason Y Tann, Lik-Wei Wong, Sreedharan Sajikumar, Carlos F Ibáñez
Aberrant function of the RNA-binding protein TDP-43 has been causally linked to multiple neurodegenerative diseases. Due to its large number of targets, the mechanisms through which TDP-43 malfunction cause disease are unclear. Here, we report that knockdown, aggregation, or disease-associated mutation of TDP-43 all impair intracellular sorting and activity-dependent secretion of the neurotrophin brain-derived neurotrophic factor (BDNF) through altered splicing of the trafficking receptor Sortilin. Adult mice lacking TDP-43 specifically in hippocampal CA1 show memory impairment and synaptic plasticity defects that can be rescued by restoring Sortilin splicing or extracellular BDNF...
January 28, 2019: EMBO Journal
Mathilde Règue-Guyon, Laurence Lanfumey, Raymond Mongeau
This review examines the epigenetic of neurotrophin signaling in anxiety, affective disorders and related symptoms associated with drug addiction, in particular alcoholism. It is first important to understand the epigenetics of aversion memories, as they are so central to anxiety and affective disorders symptomology. The crucial role of neurotrophins in memory formation, in particular the brain-derived nerve growth factor (BDNF), is explored at the physiological and behavioral levels. Numerous studies describe how various epigenetic phenomena, mainly histone acetylation, histone methylation, DNA methylation, but also other less known epigenetic phenomena such as histone poly[ADP]-ribosylation and 5-HT2C receptor pre-mRNA editing, exert significant regulatory roles in aversion memory and fear extinction memory formation...
2018: Progress in Molecular Biology and Translational Science
Faiza Mumtaz, Muhammad Imran Khan, Muhammad Zubair, Ahmad Reza Dehpour
The brain is a vital organ, susceptible to alterations under genetic influences and environmental experiences. Social isolation (SI) acts as a stressor which results in alterations in reactivity to stress, social behavior, function of neurochemical and neuroendocrine system, physiological, anatomical and behavioral changes in both animal and humans. During early stages of life, acute or chronic SIS has been proposed to show signs and symptoms of psychiatric and neurological disorders such as anxiety, depression, schizophrenia, epilepsy and memory loss...
September 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Giuseppina Talarico, Alessandro Trebbastoni, Giuseppe Bruno, Carlo de Lena
The pathogenesis of Alzheimer's disease (AD) is somewhat complex and has yet to be fully understood. As the effectiveness of the therapy currently available for AD has proved to be limited, the need for new drugs has become increasingly urgent. The modulation of the endogenous cannabinoid system (ECBS) is one of the potential therapeutic approaches that is attracting a growing amount of interest. The ECBS consists of endogenous compounds and receptors. The receptors CB1 and CB2 have already been well characterized: CB1 receptors, which are abundant in the brain, particularly in the hippocampus, basal ganglia and cerebellum, regulate memory function and cognition...
July 2, 2018: Current Neuropharmacology
R Ward, Y Abdul, A Ergul
Diabetes increases the risk and worsens the progression of cognitive impairment. The hippocampus is an important domain for learning and memory. We previously showed that endothelin-1 (ET-1) reduced diabetes-induced inflammation in hippocampal neurons, suggesting a neuroprotective effect. Given that neurons and endothelial cells within the neurovascular unit depend on each other for proper function, we investigated the effect of ET-1 on brain-derived neurotrophic factor (BDNF) synthesis, a key neurotrophin and prosurvival factor, in neuronal (HT22 hippocampal neurons) and brain microvascular endothelial (BMEC-5i) cells under normal and diabetes-mimicking (high glucose plus palmitate) conditions...
June 27, 2018: Physiological Research
Lin-Lin Shen, Noralyn B Mañucat-Tan, Shi-Hao Gao, Wei-Wei Li, Fan Zeng, Chi Zhu, Jun Wang, Xian-Le Bu, Yu-Hui Liu, Chang-Yue Gao, Zhi-Qiang Xu, Larisa Bobrovskaya, Peng Lei, Jin-Tai Yu, Weihong Song, Hua-Dong Zhou, Xiu-Qing Yao, Xin-Fu Zhou, Yan-Jiang Wang
Tau pathology is characterized as a form of frontotemporal lobar degeneration (FTLD) known as FTLD-tau. The underlying pathogenic mechanisms are not known and no therapeutic interventions are currently available. Here, we report that the neurotrophin receptor p75NTR plays a critical role in the pathogenesis of FTLD-tau. The expression of p75NTR and the precursor of nerve growth factor (proNGF) were increased in the brains of FTLD-tau patients and mice (P301L transgenic). ProNGF-induced tau phosphorylation via p75NTR in vitro, which was associated with the AKT/glycogen synthase kinase (GSK)3β pathway...
August 2018: Molecular Psychiatry
Zhijun Lu, Jihui Sun, Yichun Xin, Ken Chen, Wen Ding, Yujia Wang
The aim of the present study was to confirm that sevoflurane induces memory impairment in the postnatal developing mouse brain and determine its mechanism of action. C57BL/6 mice 7 days old were randomly assigned into a 2.6% sevoflurane (n=68), a 1.3% sevoflurane (n=68) and a control (n=38) group. Blood gas analysis was performed to evaluate hypoxia and respiratory depression during anesthesia in 78 mice. Measurements for expression of caspase-3 by immunohistochemistry, cleavage of poly adenosine diphosphate-ribose polymerase (PARP) by western blotting, as well as levels of brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor type 2 (Ntrk2), pro-BDNF, p75 neurotrophin receptor (p75NTR) and protein kinase B (PKB/Akt) by enzyme-linked immunosorbent assay were performed in the hippocampus of 12 mice from each group...
May 2018: Experimental and Therapeutic Medicine
Paul D Loprinzi, Emily Frith
One of the most amazing aspects of the human brain is its ability to learn information and use it to change behaviour. A key neurotrophin that influences memory function is brain-derived neurotrophic factor (BDNF). This review briefly discusses the mechanistic role that BDNF may play in facilitating learning and memory. We also describe the role of exercise on this relationship. As discussed herein, BDNF may influence memory via BDNF-induced alterations in membrane receptor expression and translocation, as well as activating several pathways (PLC-y, PI3K, ERK) that act together to facilitate cellular effects that influence synaptic plasticity...
May 2, 2018: Clinical Physiology and Functional Imaging
Michelle T Tong, Tae-Young P Kim, Thomas A Cleland
Long-term fear memory formation in the hippocampus and neocortex depends upon brain-derived neurotrophic factor (BDNF) signaling after acquisition. Incremental, appetitive odor discrimination learning is thought to depend substantially on the differentiation of adult-born neurons within the olfactory bulb (OB)-a process that is closely associated with BDNF signaling. We sought to elucidate the role of neurotrophin signaling within the OB on odor memory consolidation. Male mice were trained on odor-reward associative discriminations after bilateral infusion of the kinase inhibitor K252a, or vehicle control, into the OB...
May 2018: Learning & Memory
Bianca Pfaffenseller, Flavio Kapczinski, Amelia L Gallitano, Fábio Klamt
Bipolar disorder (BD) is a severe psychiatric illness with a consistent genetic influence, involving complex interactions between numerous genes and environmental factors. Immediate early genes (IEGs) are activated in the brain in response to environmental stimuli, such as stress. The potential to translate environmental stimuli into long-term changes in brain has led to increased interest in a potential role for these genes influencing risk for psychiatric disorders. Our recent finding using network-based approach has shown that the regulatory unit of early growth response gene 3 ( EGR3 ) of IEGs family was robustly repressed in postmortem prefrontal cortex of BD patients...
2018: Frontiers in Behavioral Neuroscience
Oliver von Bohlen Und Halbach, Viola von Bohlen Und Halbach
Neurotrophins, including brain-derived neurotrophic factor (BDNF), are expressed in the hippocampus, as well as their precursors, the pro-neurotrophins. The neurotrophins signal through specific tyrosine kinase receptors and the low affinity receptor p75NTR. Moreover, the pro-neurotrophins are considered to be biologically active by signaling through specific receptors. The neurotrophins, especially BDNF, are involved in processes related to learning and memory. Furthermore, it is thought that BDNF also plays a crucial role in major depression...
September 2018: Cell and Tissue Research
Jamileth Y More, Barbara A Bruna, Pedro E Lobos, José L Galaz, Paula L Figueroa, Silvia Namias, Gina L Sánchez, Genaro C Barrientos, José L Valdés, Andrea C Paula-Lima, Cecilia Hidalgo, Tatiana Adasme
AIMS: Previous studies indicate that hippocampal synaptic plasticity and spatial memory processes entail calcium release from intracellular stores mediated by ryanodine receptor (RyR) channels. In particular, RyR-mediated Ca2+ release is central for the dendritic spine remodeling induced by brain-derived neurotrophic factor (BDNF), a neurotrophin that stimulates complex signaling pathways leading to memory-associated protein synthesis and structural plasticity. To examine if upregulation of ryanodine receptor type-2 (RyR2) channels and the spine remodeling induced by BDNF entail reactive oxygen species (ROS) generation, and to test if RyR2 downregulation affects BDNF-induced spine remodeling and spatial memory...
October 20, 2018: Antioxidants & Redox Signaling
Mikhail Stepanichev, Mikhail Onufriev, Viktor Aniol, Sofia Freiman, Hemma Brandstaetter, Stefan Winter, Natalia Lazareva, Alla Guekht, Natalia Gulyaeva
BACKGROUND: Aging is associated with some cognitive decline and enhanced risk of development of neurodegenerative diseases. It is assumed that altered metabolism and functions of neurotrophin systems may underlie these age-related functional and structural modifications. CerebrolysinTM (CBL) is a neuropeptide mixture with neurotrophic effects, which is widely used for the treatment of stroke and traumatic brain injury patients. It is also evident that CBL has an overall beneficial effect and a favorable benefit-risk ratio in patients with dementia...
2017: Restorative Neurology and Neuroscience
J M Schilling, A Kassan, C Mandyam, M L Pearn, A Voong, G G Grogman, V B Risbrough, I R Niesman, H H Patel, P M Patel, B P Head
Background: Isoflurane is widely used for anaesthesia in humans. Isoflurane exposure of rodents prior to post-natal day 7 (PND7) leads to widespread neurodegeneration in laboratory animals. Previous data from our laboratory suggest an attenuation of apoptosis with the p75 neurotrophin receptor (p75NTR) inhibitor TAT-Pep5. We hypothesized that isoflurane toxicity leads to behavioural and cognitive abnormalities and can be rescued with pre-anaesthesia administration of TAT-Pep5. Methods: Neonatal mouse pups were pretreated with either TAT-Pep5 (25 μl, 10 μM i...
September 1, 2017: British Journal of Anaesthesia
Debmalya Barh, María E García-Solano, Sandeep Tiwari, Antaripa Bhattacharya, Neha Jain, Daniel Torres-Moreno, Belén Ferri, Artur Silva, Vasco Azevedo, Preetam Ghosh, Kenneth Blum, Pablo Conesa-Zamora, George Perry
The Transcription factor BarH like homeobox 1 (BARHL1) is overexpressed in medulloblastoma and plays a role in neurogenesis. However, much about the BARHL1 regulatory networks and their functions in neurodegenerative and neoplastic disorders is not yet known. In this study, using a tissue microarray (TMA), we report for the first time that BARHL1 is downregulated in hormone-negative breast cancers and Alzheimer's disease (AD). Furthermore, using an integrative bioinformatics approach and mining knockout mouse data, we show that: (i) BARHL1 and Estrogen Receptor 1 (ESR1) may constitute a network that regulates Neurotrophin 3 (NTF3)- and Brain Derived Neurotrophic Factor (BDNF)-mediated neurogenesis and neural survival; (ii) this is probably linked to AD pathways affecting aberrant post-translational modifications including SUMOylation and ubiquitination; (iii) the BARHL1-ESR1 network possibly regulates β-amyloid metabolism and memory; and (iv) hsa-mir-18a, having common key targets in the BARHL1-ESR1 network and AD pathway, may modulate neuron death, reduce β-amyloid processing and might also be involved in hearing and cognitive decline associated with AD...
September 28, 2017: Genes
Fiorenza Stagni, Andrea Giacomini, Sandra Guidi, Marco Emili, Beatrice Uguagliati, Maria Elisa Salvalai, Valeria Bortolotto, Mariagrazia Grilli, Roberto Rimondini, Renata Bartesaghi
Intellectual disability is the unavoidable hallmark of Down syndrome (DS), with a heavy impact on public health. Reduced neurogenesis and impaired neuron maturation are considered major determinants of altered brain function in DS. Since the DS brain starts at a disadvantage, attempts to rescue neurogenesis and neuron maturation should take place as soon as possible. The brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a key role in brain development by specifically binding to tropomyosin-related kinase receptor B (TrkB)...
December 2017: Experimental Neurology
Khalil Saadipour, Noralyn B Mañucat-Tan, Yoon Lim, Damien J Keating, Kevin S Smith, Jin-Hua Zhong, Hong Liao, Larisa Bobrovskaya, Yan-Jiang Wang, Moses V Chao, Xin-Fu Zhou
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive deposition of amyloid beta (Aβ) and dysregulation of neurotrophic signaling, causing synaptic dysfunction, loss of memory, and cell death. The expression of p75 neurotrophin receptor is elevated in the brain of AD patients, suggesting its involvement in this disease. However, the exact mechanism of its action is not yet clear. Here, we show that p75 interacts with beta-site amyloid precursor protein cleaving enzyme-1 (BACE1), and this interaction is enhanced in the presence of Aβ...
February 2018: Journal of Neurochemistry
Suzana Ulian-Benitez, Simon Bishop, Istvan Foldi, Jill Wentzell, Chinenye Okenwa, Manuel G Forero, Bangfu Zhu, Marta Moreira, Mark Phizacklea, Graham McIlroy, Guiyi Li, Nicholas J Gay, Alicia Hidalgo
Neurotrophism, structural plasticity, learning and long-term memory in mammals critically depend on neurotrophins binding Trk receptors to activate tyrosine kinase (TyrK) signaling, but Drosophila lacks full-length Trks, raising the question of how these processes occur in the fly. Paradoxically, truncated Trk isoforms lacking the TyrK predominate in the adult human brain, but whether they have neuronal functions independently of full-length Trks is unknown. Drosophila has TyrK-less Trk-family receptors, encoded by the kekkon (kek) genes, suggesting that evolutionarily conserved functions for this receptor class may exist...
August 2017: PLoS Genetics
Przemysław Kowiański, Grażyna Lietzau, Ewelina Czuba, Monika Waśkow, Aleksandra Steliga, Janusz Moryś
Brain-derived neurotrophic factor (BDNF) is one of the most widely distributed and extensively studied neurotrophins in the mammalian brain. Among its prominent functions, one can mention control of neuronal and glial development, neuroprotection, and modulation of both short- and long-lasting synaptic interactions, which are critical for cognition and memory. A wide spectrum of processes are controlled by BDNF, and the sometimes contradictory effects of its action can be explained based on its specific pattern of synthesis, comprising several intermediate biologically active isoforms that bind to different types of receptor, triggering several signaling pathways...
April 2018: Cellular and Molecular Neurobiology
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