BDNF mRNA abundance regulated by antidromic action potentials and AP-LTD in hippocampus

Bukalo, Olena; Lee, Philip R.; Fields, R. Douglas

doi:10.1016/j.neulet.2016.10.023

Cited by 8 publications

(12 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Both Egr3 and BDNF play critical roles in hippocampal synaptic plasticity, a process associated with memory formation. Specifically, long-term depression, a form of hippocampal plasticity that is facilitated by novelty and stress exposure, requires Egr3 , and is stimulated by the immature form of BDNF, proBDNF ( Kim et al, 1996 ; Woo et al, 2005 ; Gallitano-Mendel et al, 2007 ; Yang et al, 2014 ; Bukalo et al, 2016 ). The results of these, and many other studies, have led to the hypothesis that BDNF may be a critical molecule in mediating the therapeutic effects of psychiatric therapies, including ECT ( Bocchio-Chiavetto et al, 2006 ; Li et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

“…This finding is of interest as both Egr3 and Bdnf share several common features. These include essential roles in hippocampal long-term depression ( Gallitano-Mendel et al, 2007 ; Novkovic et al, 2015 ; Bukalo et al, 2016 ) calcium-signaling-dependent activation ( Mittelstadt and Ashwell, 1998 ; Shieh et al, 1998 ), and genetic association with schizophrenia ( Gratacos et al, 2007 ; Yamada et al, 2007 ; Kim et al, 2010 ; Ning et al, 2012 ; Zhang et al, 2012 ; Huentelman et al, 2015 ). We have hypothesized that both Bdnf and Egr3 are crucial components of a biological pathway implicated in mental illness risk ( Marballi and Gallitano, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The Immediate Early Gene Egr3 Is Required for Hippocampal Induction of Bdnf by Electroconvulsive Stimulation

Meyers¹,

Marballi²,

Brunwasser³

et al. 2018

Front. Behav. Neurosci.

View full text Add to dashboard Cite

Early growth response 3 (Egr3) is an immediate early gene (IEG) that is regulated downstream of a cascade of genes associated with risk for psychiatric disorders, and dysfunction of Egr3 itself has been implicated in schizophrenia, bipolar disorder, and depression. As an activity-dependent transcription factor, EGR3 is poised to regulate the neuronal expression of target genes in response to environmental events. In the current study, we sought to identify a downstream target of EGR3 with the goal of further elucidating genes in this biological pathway relevant for psychiatric illness risk. We used electroconvulsive stimulation (ECS) to induce high-level expression of IEGs in the brain, and conducted expression microarray to identify genes differentially regulated in the hippocampus of Egr3-deficient (-/-) mice compared to their wildtype (WT) littermates. Our results replicated previous work showing that ECS induces high-level expression of the brain-derived neurotrophic factor (Bdnf) in the hippocampus of WT mice. However, we found that this induction is absent in Egr3-/- mice. Quantitative real-time PCR (qRT-PCR) validated the microarray results (performed in males) and replicated the findings in two separate cohorts of female mice. Follow-up studies of activity-dependent Bdnf exons demonstrated that ECS-induced expression of both exons IV and VI requires Egr3. In situ hybridization demonstrated high-level cellular expression of Bdnf in the hippocampal dentate gyrus following ECS in WT, but not Egr3-/-, mice. Bdnf promoter analysis revealed eight putative EGR3 binding sites in the Bdnf promoter, suggesting a mechanism through which EGR3 may directly regulate Bdnf gene expression. These findings do not appear to result from a defect in the development of hippocampal neurons in Egr3-/- mice, as cell counts in tissue sections stained with anti-NeuN antibodies, a neuron-specific marker, did not differ between Egr3-/- and WT mice. In addition, Sholl analysis and counts of dendritic spines in golgi-stained hippocampal sections revealed no difference in dendritic morphology or synaptic spine density in Egr3-/-, compared to WT, mice. These findings indicate that Egr3 is required for ECS-induced expression of Bdnf in the hippocampus and suggest that Bdnf may be a downstream gene in our previously identified biologically pathway for psychiatric illness susceptibility.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Immediate Early Gene Egr3 Is Required for Hippocampal Induction of Bdnf by Electroconvulsive Stimulation

Meyers¹,

Marballi²,

Brunwasser³

et al. 2018

Front. Behav. Neurosci.

View full text Add to dashboard Cite

show abstract

“…7). Особенностью дендритов пирамидальных нейронов также является то, что они могут выделять сигнальные молекулы (напр., эндоканнабиноиды), которые проходят в обратном направлении через химический синапс к аксону пресинаптического нейрона [161][162][163][164][165][166][167].…”

Section: рис 6 электронотранспортная цепь митохондрийunclassified

Fundamentals of the modern theory of the phenomenon of "pain" from the perspective of a systematic approach. Neurophysiological basis. Part 1: A brief presentation of key subcellular and cellular ctructural elements of the central nervous system.

Poberezhnyi

Марчук

Shvidyuk

et al. 2019

PMJUA

View full text Add to dashboard Cite

The phenomenon of “pain” is a psychophysiological phenomenon that is actualized in the mind of a person as a result of the systemic response of his body to certain external and internal stimuli. The heart of the corresponding mental processes is certain neurophysiological processes, which in turn are caused by a certain form of the systemic structural and functional organization of the central nervous system (CNS). Thus, the systemic structural and functional organization of the central nervous system of a person, determining the corresponding psychophysiological state in a specific time interval, determines its psycho-emotional states or reactions manifested by the pain phenomenon. The nervous system of the human body has a hierarchical structure and is a morphologically and functionally complete set of different, interconnected, nervous and structural formations. The basis of the structural formations of the nervous system is nervous tissue. It is a system of interconnected differentials of nerve cells, neuroglia and glial macrophages, providing specific functions of perception of stimulation, excitation, generation of nerve impulses and its transmission. The neuron and each of its compartments (spines, dendrites, catfish, axon) is an autonomous, plastic, active, structural formation with complex computational properties. One of them – dendrites – plays a key role in the integration and processing of information. Dendrites, due to their morphology, provide neurons with unique electrical and plastic properties and cause variations in their computational properties. The morphology of dendrites: 1) determines – a) the number and type of contacts that a particular neuron can form with other neurons; b) the complexity, diversity of its functions; c) its computational operations; 2) determines – a) variations in the computational properties of a neuron (variations of the discharges between bursts and regular forms of pulsation); b) back distribution of action potentials. Dendritic spines can form synaptic connection – one of the main factors for increasing the diversity of forms of synaptic connections of neurons. Their volume and shape can change over a short period of time, and they can rotate in space, appear and disappear by themselves. Spines play a key role in selectively changing the strength of synaptic connections during the memorization and learning process. Glial cells are active participants in diffuse transmission of nerve impulses in the brain. Astrocytes form a three-dimensional, functionally “syncytia-like” formation, inside of which there are neurons, thus causing their specific microenvironment. They and neurons are structurally and functionally interconnected, based on which their permanent interaction occurs. Oligodendrocytes provide conditions for the generation and transmission of nerve impulses along the processes of neurons and play a significant role in the processes of their excitation and inhibition. Microglial cells play an important role in the formation of the brain, especially in the formation and maintenance of synapses. Thus, the CNS should be considered as a single, functionally “syncytia-like”, structural entity. Because the three-dimensional distribution of dendritic branches in space is important for determining the type of information that goes to a neuron, it is necessary to consider the three-dimensionality of their structure when analyzing the implementation of their functions.

show abstract

“…As described in the sections below, numerous downstream effectors of NMDAR activation have also been shown to be critical for activity dependent LTD. These include CN, EGR3, ARC, serum response factor (SRF) and BDNF (Zeng et al, 2001 ; Etkin et al, 2006 ; Plath et al, 2006 ; Gallitano-Mendel et al, 2007 ; Beazely et al, 2009 ; Mizui et al, 2015 ; Novkovic et al, 2015 ; Bukalo et al, 2016 ; Kojima and Mizui, 2017 ). The roles of several of the proteins that comprise our proposed pathway for schizophrenia risk are not limited to this form of synaptic plasticity.…”

Section: Long-term Depression Stress and Memorymentioning

confidence: 99%

“…It was recently reported that BDNF-deficient mice display defects in hippocampal LTD (Novkovic et al, 2015 ; Bukalo et al, 2016 ). In addition, exogenous application of the precursor (pro) peptide of BDNF facilitates development of LTD, a process that requires function of GLUN2B containing NMDARs (Mizui et al, 2015 ; Kojima and Mizui, 2017 ).…”

Section: Additional Genes That Interact With the Pathwaymentioning

confidence: 99%

Immediate Early Genes Anchor a Biological Pathway of Proteins Required for Memory Formation, Long-Term Depression and Risk for Schizophrenia

Marballi

Gallitano

2018

Front. Behav. Neurosci.

View full text Add to dashboard Cite

While the causes of myriad medical and infectious illnesses have been identified, the etiologies of neuropsychiatric illnesses remain elusive. This is due to two major obstacles. First, the risk for neuropsychiatric disorders, such as schizophrenia, is determined by both genetic and environmental factors. Second, numerous genes influence susceptibility for these illnesses. Genome-wide association studies have identified at least 108 genomic loci for schizophrenia, and more are expected to be published shortly. In addition, numerous biological processes contribute to the neuropathology underlying schizophrenia. These include immune dysfunction, synaptic and myelination deficits, vascular abnormalities, growth factor disruption, and N-methyl-D-aspartate receptor (NMDAR) hypofunction. However, the field of psychiatric genetics lacks a unifying model to explain how environment may interact with numerous genes to influence these various biological processes and cause schizophrenia. Here we describe a biological cascade of proteins that are activated in response to environmental stimuli such as stress, a schizophrenia risk factor. The central proteins in this pathway are critical mediators of memory formation and a particular form of hippocampal synaptic plasticity, long-term depression (LTD). Each of these proteins is also implicated in schizophrenia risk. In fact, the pathway includes four genes that map to the 108 loci associated with schizophrenia: GRIN2A, nuclear factor of activated T-cells (NFATc3), early growth response 1 (EGR1) and NGFI-A Binding Protein 2 (NAB2); each of which contains the “Index single nucleotide polymorphism (SNP)” (most SNP) at its respective locus. Environmental stimuli activate this biological pathway in neurons, resulting in induction of EGR immediate early genes: EGR1, EGR3 and NAB2. We hypothesize that dysfunction in any of the genes in this pathway disrupts the normal activation of Egrs in response to stress. This may result in insufficient electrophysiologic, immunologic, and neuroprotective, processes that these genes normally mediate. Continued adverse environmental experiences, over time, may thereby result in neuropathology that gives rise to the symptoms of schizophrenia. By combining multiple genes associated with schizophrenia susceptibility, in a functional cascade triggered by neuronal activity, the proposed biological pathway provides an explanation for both the polygenic and environmental influences that determine the complex etiology of this mental illness.

show abstract

BDNF mRNA abundance regulated by antidromic action potentials and AP-LTD in hippocampus

Cited by 8 publications

References 41 publications

The Immediate Early Gene Egr3 Is Required for Hippocampal Induction of Bdnf by Electroconvulsive Stimulation

The Immediate Early Gene Egr3 Is Required for Hippocampal Induction of Bdnf by Electroconvulsive Stimulation

Fundamentals of the modern theory of the phenomenon of "pain" from the perspective of a systematic approach. Neurophysiological basis. Part 1: A brief presentation of key subcellular and cellular ctructural elements of the central nervous system.

Immediate Early Genes Anchor a Biological Pathway of Proteins Required for Memory Formation, Long-Term Depression and Risk for Schizophrenia

Contact Info

Product

Resources

About