immediate early genes
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2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Emmanuel S. Ojo ◽  
Ismail O. Ishola ◽  
Olasunmbo Afolayan ◽  
Ayorinde B. James ◽  
Benneth Ben-Azu ◽  
...  

Abstract Objectives This study investigates the influence of Cnestis ferruginea (CF) on kainic acid (KA)-induced immediate early genes (IEGs) associated with hippocampal sclerosis in temporal lobe epilepsy (TLE) in mice. Methods Animals were randomly divided into preventive treatment; vehicle (10 mL/kg, p.o.) or CF (400 mg/kg, p.o.) for three consecutive days before KA (5 mg/kg, i.p.) on days 4 and 5. In the reversal model, KA (5 mg/kg, i.p.) was administered on days 1 and 2 before CF (400 mg/kg) administration on days 3–5. Animals were euthanized on day 5, 6 h after KA exposure in preventive model and 1 h after CF administration in reversal model to estimate markers of IEGs. Results KA upregulated the expression of c-Fos protein by 3.32-, 9.45-, 8.13-, and 8.66-fold in the hippocampal CA1, CA2, CA3, and DG regions, respectively. Also, KA elevated inducible nitric oxide synthase protein expression by 10.9-, 10.6-, 9.78-, and 9.51-fold. Besides, mRNA expression of brain-derived neurotrophic factors and heat shock protein was increased by 2.38- and 1.39-fold, respectively, after exposure to KA which were attenuated by CF. Conclusions CF attenuated KA-induced IEGs and could be used as an adjunct in TLE.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Edyta Balcerek ◽  
Urszula Włodkowska ◽  
Rafał Czajkowski

AbstractThe ability to form, retrieve and update autobiographical memories is one of the most fascinating features of human behavior. Spatial memory, the ability to remember the layout of the external environment and to navigate within its boundaries, is closely related to the autobiographical memory domain. It is served by an overlapping brain circuit, centered around the hippocampus (HPC) where the cognitive map index is stored. Apart from the hippocampus, several cortical structures participate in this process. Their relative contribution is a subject of intense research in both humans and animal models. One of the most widely studied regions is the retrosplenial cortex (RSC), an area in the parietal lobe densely interconnected with the hippocampal formation. Several methodological approaches have been established over decades in order to investigate the cortical aspects of memory. One of the most successful techniques is based on the analysis of brain expression patterns of the immediate early genes (IEGs). The common feature of this diverse group of genes is fast upregulation of their mRNA translation upon physiologically relevant stimulus. In the central nervous system they are rapidly triggered by neuronal activity and plasticity during learning. There is a widely accepted consensus that their expression level corresponds to the engagement of individual neurons in the formation of memory trace. Imaging of the IEGs might therefore provide a picture of an emerging memory engram. In this review we present the overview of IEG mapping studies of retrosplenial cortex in rodent models. We begin with classical techniques, immunohistochemical detection of protein and fluorescent in situ hybridization of mRNA. We then proceed to advanced methods where fluorescent genetically encoded IEG reporters are chronically followed in vivo during memory formation. We end with a combination of genetic IEG labelling and optogenetic approach, where the activity of the entire engram is manipulated. We finally present a hypothesis that attempts to unify our current state of knowledge about the function of RSC.


2021 ◽  
Vol 12 ◽  
Author(s):  
Nuria Nadal-Gratacós ◽  
Ana Sofia Alberto-Silva ◽  
Míriam Rodríguez-Soler ◽  
Edurne Urquizu ◽  
Maria Espinosa-Velasco ◽  
...  

Several new synthetic cathinones, which mimic the effect of classical psychostimulants such as cocaine or MDMA, have appeared in the global illicit drug market in the last decades. In fact, the illicit drug market is continually evolving by constantly adding small modifications to the common chemical structure of synthetic cathinones. Thus, the aim of this study was to investigate the in vitro and in vivo structure–activity relationship (SAR) of six novel synthetic cathinones currently popular as recreational drugs, pentedrone, pentylone, N-ethyl-pentedrone (NEPD), N-ethyl-pentylone (NEP), 4-methyl-pentedrone (4-MPD), and 4-methyl-ethylaminopentedrone (4-MeAP), which structurally differ in the absence or presence of different aromatic substituents and in their amino terminal group. Human embryonic kidney (HEK293) cells expressing the human isoforms of SERT and DAT were used for the uptake inhibition and release assays. Moreover, Swiss CD-1 mice were used to investigate the psychostimulant effect, rewarding properties (3, 10, and 30 mg/kg, i.p.), and the induction of immediate-early genes (IEGs), such as Arc and c-fos in the dorsal striatum (DS) and ventral striatum (VS) as well as bdnf in the medial prefrontal cortex (mPFC), of the test compounds. Our results demonstrated that all tested synthetic cathinones are potent dopamine (DA) uptake inhibitors, especially the N-ethyl analogs, while the ring-substituted cathinones tested showed higher potency as SERT inhibitors than their no ring-substituted analogs. Moreover, unlike NEP, the remaining test compounds showed clear “hybrid” properties, acting as DAT blockers but SERT substrates. Regarding the locomotion, NEP and NEPD were more efficacious (10 mg/kg) than their N-methyl analogs, which correlates with their higher potency inhibiting the DAT and an overexpression of Arc levels in the DS and VS. Furthermore, all compounds tested induced an increase in c-fos expression in the DS, except for 4-MPD, the least effective compound in inducing hyperlocomotion. Moreover, NEP induced an up-regulation of bdnf in the mPFC that correlates with its 5-HTergic properties. Finally, the present study demonstrated for the first time that NEP, 4-MPD, and 4-MeAP induce reward in mice. Altogether, this study provides valuable information about the mechanism of action and psychostimulant and rewarding properties as well as changes in the expression of IEGs related to addiction induced by novel second-generation synthetic cathinones.


2021 ◽  
Vol 15 ◽  
Author(s):  
Shuiyu Li ◽  
Songping Yao ◽  
Qiuying Zhou ◽  
Toru Takahata

Because at least some squirrel monkeys lack ocular dominance columns (ODCs) in the striate cortex (V1) that are detectable by cytochrome oxidase (CO) histochemistry, the functional importance of ODCs on stereoscopic 3-D vision has been questioned. However, conventional CO histochemistry or trans-synaptic tracer study has limited capacity to reveal cortical functional architecture, whereas the expression of immediate-early genes (IEGs), c-FOS and ZIF268, is more directly responsive to neuronal activity of cortical neurons to demonstrate ocular dominance (OD)-related domains in V1 following monocular inactivation. Thus, we wondered whether IEG expression would reveal ODCs in the squirrel monkey V1. In this study, we first examined CO histochemistry in V1 of five squirrel monkeys that were subjected to monocular enucleation or tetrodotoxin (TTX) treatment to address whether there is substantial cross-individual variation as reported previously. Then, we examined the IEG expression of the same V1 tissue to address whether OD-related domains are revealed. As a result, staining patterns of CO histochemistry were relatively homogeneous throughout layer 4 of V1. IEG expression was also moderate and homogeneous throughout layer 4 of V1 in all cases. On the other hand, the IEG expression was patchy in accordance with CO blobs outside layer 4, particularly in infragranular layers, although they may not directly represent OD clusters. Squirrel monkeys remain an exceptional species among anthropoid primates with regard to OD organization, and thus are potentially good subjects to study the development and function of ODCs.


2021 ◽  
Vol 81 (19) ◽  
pp. 4041-4058.e15
Author(s):  
Hongshan Guo ◽  
Gabriel Golczer ◽  
Ben S. Wittner ◽  
Adam Langenbucher ◽  
Marcus Zachariah ◽  
...  

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