scholarly journals Neonatal Clonazepam Administration Induced Long-Lasting Changes in GABAA and GABAB Receptors

2020 ◽  
Vol 21 (9) ◽  
pp. 3184
Author(s):  
Hana Kubová ◽  
Zdeňka Bendová ◽  
Simona Moravcová ◽  
Dominika Pačesová ◽  
Luisa Rocha ◽  
...  

Benzodiazepines (BZDs) are widely used in patients of all ages. Unlike adults, neonatal animals treated with BZDs exhibit a variety of behavioral deficits later in life; however, the mechanisms underlying these deficits are poorly understood. This study aims to examine whether administration of clonazepam (CZP; 1 mg/kg/day) in 7–11-day-old rats affects Gama aminobutyric acid (GABA)ergic receptors in both the short and long terms. Using RT-PCR and quantitative autoradiography, we examined the expression of the selected GABAA receptor subunits (α1, α2, α4, γ2, and δ) and the GABAB B2 subunit, and GABAA, benzodiazepine, and GABAB receptor binding 48 h, 1 week, and 2 months after treatment discontinuation. Within one week after CZP cessation, the expression of the α2 subunit was upregulated, whereas that of the δ subunit was downregulated in both the hippocampus and cortex. In the hippocampus, the α4 subunit was downregulated after the 2-month interval. Changes in receptor binding were highly dependent on the receptor type, the interval after treatment cessation, and the brain structure. GABAA receptor binding was increased in almost all of the brain structures after the 48-h interval. BZD-binding was decreased in many brain structures involved in the neuronal networks associated with emotional behavior, anxiety, and cognitive functions after the 2-month interval. Binding of the GABAB receptors changed depending on the interval and brain structure. Overall, the described changes may affect both synaptic development and functioning and may potentially cause behavioral impairment.

Insects ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 886
Author(s):  
Silvana Piersanti ◽  
Manuela Rebora ◽  
Gianandrea Salerno ◽  
Sylvia Anton

Dragonflies are hemimetabolous insects, switching from an aquatic life style as nymphs to aerial life as adults, confronted to different environmental cues. How sensory structures on the antennae and the brain regions processing the incoming information are adapted to the reception of fundamentally different sensory cues has not been investigated in hemimetabolous insects. Here we describe the antennal sensilla, the general brain structure, and the antennal sensory pathways in the last six nymphal instars of Libellula depressa, in comparison with earlier published data from adults, using scanning electron microscopy, and antennal receptor neuron and antennal lobe output neuron mass-tracing with tetramethylrhodamin. Brain structure was visualized with an anti-synapsin antibody. Differently from adults, the nymphal antennal flagellum harbors many mechanoreceptive sensilla, one olfactory, and two thermo-hygroreceptive sensilla at all investigated instars. The nymphal brain is very similar to the adult brain throughout development, despite the considerable differences in antennal sensilla and habitat. Like in adults, nymphal brains contain mushroom bodies lacking calyces and small aglomerular antennal lobes. Antennal fibers innervate the antennal lobe similar to adult brains and the gnathal ganglion more prominently than in adults. Similar brain structures are thus used in L. depressa nymphs and adults to process diverging sensory information.


2020 ◽  
Vol 10 (2) ◽  
Author(s):  
Nenad Stojiljković ◽  
Petar Mitić ◽  
Goran Sporiš

Purpose. The aim of this study is to reveal the effects of exercise on the brain structure and function in children, and to analyze methodological approach applied in the researches of this topic. Methods. This literature review provides an overview of important findings in this fast growing research domain. Results from cross-sectional, longitudinal, and interventional studies of the influence of exercise on the brain structure and function of healthy children are reviewed and discussed. Results. The majority of researches are done as cross sectional studies based on the exploring correlation between the level of physical activity and characteristics of brain structure and function. Results of the studies indicate that exercise has positive correlation with improved cognition and beneficial changes to brain function in children. Physically active children have greater white matter integrity in several white matter tracts (corpus callosum, corona radiata, and superior longitudinal fasciculus), have greater volume of gray matter in the hippocampus and basal ganglia than their physically inactive counterparts. The longitudinal/interventional studies also showed that exercise (mainly aerobic) improve cognitive performance of children and causes changes observed on functional magnetic resonance imaging scans (fMRI) located in prefrontal and parietal regions. Conclusion. Previous researches undoubtable proved that exercise can make positive changes of the brain structures in children, specifically the volume of the hippocampus which is the center of learning and memory. Finally the researchers agree that the most influential type of exercise on changes of brain structure and functions are the aerobic exercises. 


2013 ◽  
Vol 24 (7) ◽  
pp. 1349-1358 ◽  
Author(s):  
Yinghua Yu ◽  
Yizhen Wu ◽  
Craig Patch ◽  
Zhixiang Wu ◽  
Alexander Szabo ◽  
...  

2018 ◽  
Vol 16 (4) ◽  
pp. 45-48
Author(s):  
Platon P. Khokhlov ◽  
Ilia Yu. Tissen ◽  
Andrei A. Lebedev ◽  
Eugenii R. Bychkov ◽  
Petr D. Shabanov

The aim of this investigation was to reveal correlations between some behavioral patterns and orexin concentrations in the brain structures in rats after an acute psychoemotional stress. A group of rats was placed into a chamber with a tiger python for 25 mi nutes and then as a treatment these rats received orexin A or its antagonist SB-408124 administered intranasally for 7 days. Then the quantitive indexes of behavioral patterns in open field and elevated plus maze were registered. The orexin A level was investigated in the brain structures (amygdala, hippocampus, hypothalamus) of such rats by means of high-sensitive ELISA. The correlations were assessed with Spearman’s rank correlation test. As a result, a correlation between orexin A content in the amygdala and hypothalamus and a number of ambulations (line crossings) characterizing motor activity in open field test has been revealed. Therefore, the level of orexin A in the amygdala and hypothalamus demonstrates a direct and reverse link with locomotor activity of rats respectively. Also a correlation between orexin A level in the hippocampus and amygdala and the time of staying in the dark alleys of the elevated plus maze has been revealed. So, the content of orexin A in the hippocampus and amygdala reflects anxiety level of a rat. It is concluded there is a positive correlation between the orexin A content in the limbic structures of the brain and emotional behavior of rats.


Diversity ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 34 ◽  
Author(s):  
Catherine M. Early ◽  
Ryan C. Ridgely ◽  
Lawrence M. Witmer

The shape of the brain influences skull morphology in birds, and both traits are driven by phylogenetic and functional constraints. Studies on avian cranial and neuroanatomical evolution are strengthened by data on extinct birds, but complete, 3D-preserved vertebrate brains are not known from the fossil record, so brain endocasts often serve as proxies. Recent work on extant birds shows that the Wulst and optic lobe faithfully represent the size of their underlying brain structures, both of which are involved in avian visual pathways. The endocasts of seven extinct birds were generated from microCT scans of their skulls to add to an existing sample of endocasts of extant birds, and the surface areas of their Wulsts and optic lobes were measured. A phylogenetic prediction method based on Bayesian inference was used to calculate the volumes of the brain structures of these extinct birds based on the surface areas of their overlying endocast structures. This analysis resulted in hyperpallium volumes of five of these extinct birds and optic tectum volumes of all seven extinct birds. Phylogenetic ANCOVA (phyANCOVA) were performed on regressions of the brain-structure volumes and endocast structure surface areas on various brain size metrics to determine if the relative sizes of these structures in any extinct birds were significantly different from those of the extant birds in the sample. Phylogenetic ANCOVA indicated that no extinct birds studied had relative hyperpallial volumes that were significantly different from the extant sample, nor were any of their optic tecta relatively hypertrophied. The optic tectum of Dinornis robustus was significantly smaller relative to brain size than any of the extant birds in our sample. This study provides an analytical framework for testing the hypotheses of potential functional behavioral capabilities of other extinct birds based on their endocasts.


1993 ◽  
Vol 69 (2) ◽  
pp. 630-635 ◽  
Author(s):  
N. A. Lambert ◽  
W. A. Wilson

1. The effects of the K+ channel blocker 9-amino-1,2,3,4-tetrahydroacridine (THA) on the actions of baclofen and gamma-aminobutyric acid (GABA) at post- and presynaptic GABAB receptors were studied with whole-cell voltage-clamp recording in area CA3 of rat hippocampal slices. 2. The effect of THA on postsynaptic GABAB receptor-mediated responses was studied in neurons perfused internally with potassium gluconate and guanosine triphosphate (GTP). At a holding potential of -70 mV, the GABAB receptor agonist (+/-)-baclofen (30 microM) induced an outward current and increased membrane conductance. In the presence of the excitatory amino acid receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and (+/-)-2-amino-5-phosphonovalerate (APV), stimulation in stratum pyramidale or proximal stratum radiatum evoked GABAA receptor-mediated, fast monosynaptic inhibitory postsynaptic currents (IPSCs) and GABAB receptor-mediated, late monosynaptic IPSCs. THA (0.3 mM) blocked the baclofen-induced current and conductance increase and GABAB receptor-mediated IPSCs. 3. The effect of THA on presynaptic GABAB receptor-mediated responses was studied in neurons perfused internally with Cs+ and lidocaine N-ethyl bromide (QX-314), which blocked post-synaptic GABAB receptor-mediated responses. Stimulation in the presence of DNQX and APV evoked GABAA receptor-mediated IPSCs; when pairs of stimuli were delivered 200 ms apart the second IPSC was depressed. Baclofen reversibly depressed IPSCs, and partially occluded paired-pulse depression of IPSCs. The GABAB receptor antagonist CGP 35348 (0.5-1.0 mM) reversed baclofen-induced depression of IPSCs and partially blocked paired-pulse depression. Baclofen-induced and paired-pulse depression of IPSCs were not by affected by THA (0.3 mM). 4. Baclofen reversibly decreased the amplitude and frequency of spontaneous monosynaptic IPSCs (sIPSCs). Depression of sIPSCs by baclofen was unchanged by THA. 5. These results indicate that THA blocks the actions of baclofen and GABA at post- but not presynaptic GABAB receptors. We conclude that post- and presynaptic GABAB receptors in area CA3 of the rat hippocampus couple to different effector mechanisms; postsynaptic GABAB receptors activate THA-sensitive K+ channels, and presynaptic GABAB receptors decrease neurotransmitter release through a THA-insensitive mechanism.


2014 ◽  
pp. 529-534 ◽  
Author(s):  
P. FÁBERA ◽  
P. MAREŠ

Activation of GABAB receptors leads to longer inhibitory postsynaptic potentials than activation of GABAA receptors. Therefore GABAB receptors may be a target for anticonvulsant therapy. The present study examined possible effects of GABAB receptor agonist SKF97541 on cortical and hippocampal epileptic afterdischarges (ADs). Epileptic ADs elicited by electrical stimulation of sensorimotor cortex or dorsal hippocampus were studied in adult male Wistar rats. Stimulation series were applied 6 times with 10- or 20-min interval. Either interval was efficient for reliable elicitation of cortical ADs but stimulation at 10-min intervals did not reliably elicit hippocampal ADs, many stimulations were without effect. SKF97541 in dose 1 mg/kg significantly prolonged cortical ADs. Duration of hippocampal ADs was not significantly changed by either dose of SKF97541 in spite of a marked myorelaxant effect of the higher dose. Our present data demonstrated that neither cortical nor hippocampal ADs in adult rats were suppressed by GABAB receptor agonist SKF97541. Proconvulsant effect on cortical ADs indicates a different role in these two brain structures. In addition, duration of refractory period for electrically-induced ADs in these two structures in adult rats is different.


1995 ◽  
Vol 73 (3) ◽  
pp. 1135-1144 ◽  
Author(s):  
S. J. Zhang ◽  
M. B. Jackson

1. We investigated gamma-aminobutyric acid (GABA) receptors using thin slice patch-clamp techniques in the swellings along axons of posterior pituitary nerve terminals. 2. Activation of the nerve terminal GABAA receptor induced a mean conductance change of 1.5 nS. Normalizing to area gave a mean conductance density of 0.38 mS/cm2. 3. Whereas GABAA receptor-mediated responses could be seen in 91% of the nerve terminals tested, GABAB receptor-mediated responses could not be detected. The GABAB receptor agonist baclofen had no effect on holding current or on voltage-activated K+ and Ca2+ channels. It is unlikely that nerve terminals of the posterior pituitary contain GABAB receptors. 4. The channel gated by the nerve terminal GABAA receptor exhibited only a single open conductance level. Only fully open and fully closed states were observed. Subconductance states typical of other GABAA receptor channels were not seen in the GABA-gated channels of posterior pituitary nerve terminals. 5. Both open time and closed time distributions were biexponential, indicating at least two open and two closed conformations of the channel. At a higher GABA concentration, long-duration openings predominated, suggesting that long-duration openings were distinguished from short-duration openings by the occupation of a greater number of agonist binding sites. 6. Sustained application of GABA desensitized the receptor with simple exponential kinetics. The time constant for desensitization was approximately 9 s for both GABA and muscimol. 7. Zinc ions at concentrations of 100 microM reduced GABA responses by only 22%. This weak sensitivity to zinc, together with a previous observation of benzodiazepine sensitivity, suggested that the nerve terminal GABAA receptor possesses a gamma-subunit. 8. Responses mediated by the GABAA receptor persist in whole terminal recordings without Mg-ATP in the pipette solution. Thus, in contrast to many other GABAA receptors, this receptor showed no rundown in the absence of ATP. 9. The GABAA receptor channel of posterior pituitary nerve terminals has many properties in common with GABAA receptors of other preparations. A number of subtle differences between the nerve terminal receptor described here and cell body receptors described elsewhere may reflect the presence of receptor protein subunits unique to nerve terminals.


1984 ◽  
Vol 112 (1) ◽  
pp. 65-93 ◽  
Author(s):  
K. F. FISCHBACH ◽  
M. HEISENBERG

The importance of the genome for behaviour has been amply demonstrated by the tools of population genetics. A deeper understanding of the relationship between genes and behaviour requires an investigation of how they influence brain development and neuronal function. This is the objective of neurogenetics. Rigid genetic control of brain structure in insects is indicated by bilateral symmetry and by the similarity of isogenic brains (in locust). In large parts of the brain (e.g. optic lobes) the role of developmental variability seems to be as limited as in nematodes, but at closer inspection, the growth of at least some brain structures (e.g. mushroom bodies) is influenced by experience, similar to the growth of some vertebrate systems. The role of individual genes for brain development and brain function is being studied in Drosophila melanogaster. Here, many single gene mutations affecting the brain and behaviour have been isolated. They either alter the development of neural circuits or modify cellular functions of neurones. Mutations of both categories are often remarkably specific (i.e. they influence only certain functional subsystems, leaving others unaffected). Therefore, functional subsystems are to some degree ontogenetic units under independent genetic control. Telling examples are sexual dimorphisms of behaviour and brain structure. The already peripheral separation of functional pathways in the brain seems to be partially due to the selective advantage of independent genetic modifiability of functions.


2007 ◽  
Vol 177 (4S) ◽  
pp. 86-87
Author(s):  
Yosuke Matsuta ◽  
Aniwar Yusup ◽  
Masaharu Nakai ◽  
Kazuya Tanase ◽  
Yoshitaka Aoki ◽  
...  
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