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Cocaine Pharmacology and Drug Interaction in the Fetal-Maternal Unit
Published in Richard J. Konkol, George D. Olsen, Prenatal Cocaine Exposure, 2020
George D. Olsen, Peter C. Schalock
Several recent papers suggest that the expression of immediate early genes (IEGs) is changed by acute and chronic cocaine exposure. IEGs are a class of genes which respond to environmental signals such as neurotransmitters and growth factors. The products of some of these genes go on to act as transcription factors for the late response genes.76 The IEGs may play a critical role in mediating stimulus-induced neuronal plasticity and have been implicated in behavioral tolerance and sensitization to cocaine.76 In this regard, cocaine is capable of causing a brief rise in mRNA of the effector IEG protein arc (activity-regulated, cytoskeleton-associated) in the striatum.77 This protein is associated with the actin cytoskeleton in the cell body and dendrites of striatal neurons. In another study using in-situ hybridization,78 the cellular phenotype in the striatum which showed increased c-fos activity after acute cocaine administration was neurons containing substance P, but not enkephalin. When IEG expression was studied in the withdrawal period, reductions of zif268 and c-fos were noted.79 This reduction lasted several hours after a single dose. If multiple cocaine doses were given, a reduction of these mRNAs was seen for several days, suggesting chronic cocaine exposure is capable of significantly lowering mRNA levels.
Central Connections of the Nuclei of the Vagus Nerve
Published in Sue Ritter, Robert C. Ritter, Charles D. Barnes, Neuroanatomy and Physiology of Abdominal Vagal Afferents, 2020
R.A. Leslie, D.J.M. Reynolds, I.N.C. Lawes
Identification of neuronal connections using lesioning techniques has been hampered by the lack of selectivity of the physical means employed to produce lesions (usually coagulation or knife cuts). Toxins such as kainic acid can be used to achieve discrete lesions which destroy neuronal cell bodies but leave fibers of passage (relatively) intact.11 Other neurotoxins exert their cytotoxic action on populations of neurons with specific uptake sites (5,7- dihydroxytryptamine for serotonergic neurons or 6-OH-dopamine for catecholaminergic neurons, for example). The use of neurotransmitter-selective lesions may well provide more evidence to unravel the complexity of neurotransmitter interactions within the paraventricular system. Another kind of approach that may be exploited is the use of functional mapping with such brain imaging techniques as radiolabeled 2-deoxyglucose uptake (Andrews et al.3 and Brizzee and Mehler8 for example, have applied this to vagal studies), and cytochrome oxidase histochemistry.68 The most recent development in this field involves the localization of immediate-early gene products using immunohistochemistry or in situ hybridization. For example, many studies have now appeared in the literature which indicate that the immediate-early gene c-fos may be selectively induced in cells of the central nervous system during neuronal activity.40
Proto-Oncogene and Onco-Suppressor Gene Expression
Published in Enrique Pimentel, Handbook of Growth Factors, 2017
Growth factors and other extracellular signaling agents are involved in regulating the expression of cellular genes, including the expression of genes associated with the control mechanisms of cell differentiation and cell proliferation. The levels of expression of certain genes, called “immediate-early” genes or early-response genes, are rapidly altered by the exposure of sensitive cells to the signaling agents. Other genes may be regulated secondarily to the early cellular response and are considered as late-response genes. Frequently, the genes regulated by growth factors and other extracellular signaling molecules are proto-oncogenes or tumor suppressor genes whose products are localized mainly in the nucleus. The nuclear localization of these products may depend on the presence of specific amino acid sequences that are required for their interaction with the nuclear pore complex.12 The proto-oncogene products Myc, Myb, Fos, Jun, Ets, and Rel function as transcription factors and their expression may be regulated at the transcriptional and/or posttranscriptional level by extracellular signaling agents. The regulation may include reversible phosphorylation/dephosphorylation of the protein.13 The p53 and RB tumor suppressor proteins are localized mainly in the nucleus, and their functions are also regulated by phosphorylation at specific amino acid residues. All these proto-oncogene and tumor suppressor gene products have an important role in growth control.
Integrating network pharmacology and in vitro model to investigate hippocampal neurotoxicity induced by atrazine
Published in Toxicology Mechanisms and Methods, 2022
To illuminate the potential biological functions of these targets, GO and KEGG enrichment analyses were performed. Results suggested that BP categories such as response to oxidative stress, and neuron apoptotic process were significantly enriched. Indeed, oxidative stress and apoptosis are widely involved in neural damage (Alhazzani et al. 2018; Liu et al. 2018). In CC categories, mitochondrial envelope and neuronal structures were significantly enriched. This was consistent with our previous study, which found that ATR exposure affected the mitochondria in hippocampal neurons (Li et al. 2019). Once the mitochondrial function dysfunctions, the main structures of neurons such as synapses and dendrites are also influenced (Janickova et al. 2020). We then found that MF categories such as transcription factor binding and RNA polymerase II transcription coactivator binding were significantly enriched. Executive functions of the hippocampus mainly depended on synaptic plasticity, which translocates transcription factors into the nucleus and leads to the transcription of immediate-early genes (Park et al. 2021).
Experience and activity-dependent control of glucocorticoid receptors during the stress response in large-scale brain networks
Published in Stress, 2021
Damien Huzard, Virginie Rappeneau, Onno C. Meijer, Chadi Touma, Margarita Arango-Lievano, Michael J. Garabedian, Freddy Jeanneteau
Mechanisms of adaptive plasticity utilize immediate early genes as first-line responders to glucocorticoid stimulation to prepare cells for a changing environment based on prior experience. For example, the MAPK specific phosphatases (Mitogen-Activated Protein Kinase Phosphatase 1/6 [MKP1/6]) are induced to terminate coincident growth factor signaling pathways converging on the GR phosphorylation code and the epigenome (Deinhardt & Jeanneteau, 2012; Jeanneteau & Deinhardt, 2011). Another example is the stress-induced transcription factors NR4A1/2/3, which shuttle in and out of the nucleus and mitochondria to coordinate metabolism and synapses number (Jeanneteau et al., 2018). Finally, actin binding proteins such as the Ca2+ sensor caldesmon and the cofilin kinase LIM-kinase 1 (LIMK1) are induced to reorganize the cytoskeleton supporting neuronal migration, differentiation, and connectivity (Fukumoto et al., 2009; Mayanagi et al., 2008; Morsink et al., 2006). Altogether, these responses set in motion the adaptive machinery that updates many attributes of neuronal function to its environment based on prior experience.
C-Fos mapping and EEG characteristics of multiple mice brain regions in pentylenetetrazol-induced seizure mice model
Published in Neurological Research, 2019
Huajun Yang, Wei Shan, Fei Zhu, Tingting Yu, Jingjing Fan, Anchen Guo, Fei Li, Xiaofeng Yang, Qun Wang
C-Fos is an immediate early gene (IEG) with activity-dependent protein expression. Expression of c-Fos is an indirect marker of neuronal activity, and as is often expressed when neurons generate the action potentials. It has been extensively used to map stimulus-induced neuronal activation [12,13]. Several studies have reported the expression of c-Fos in different brain regions during the evolution of seizures in PTZ-induced seizure models indicated multiple brain regions activity during seizure response. The subconvulsive dose of PTZ (10–40 mg/kg) induced c-Fos immunoreactivity in thalamus and hypothalamus regions of adult rats [2,14]. Repetitive intraperitoneal injections of subconvulsive doses of PTZ induced seizures including absence-like, clonic, tonic-clonic seizures and status epilepticus, and were accompanied by c-Fos expression in the hippocampal dentate gyrus, and cortex [4]. For temporal profile of c-Fos induction, seizures induced by PTZ led to increased c-Fos expression at immunohistochemical level in rodents at 30 min. Maximum expression levels were observed at 1 h and 2 h after seizure induction, returning to baseline level at 6 h [15]. A second seizure induced in rats was within the absolute or relative refractory period (1–3 h) after the first one, and triggered no change or a partial effect in c-Fos expression, suggesting some inhibitory mechanisms of neuronal activities after epileptic seizures [15].