The cannabinoid CB1 receptor biphasically modulates motor activity and regulates dopamine and glutamate release region dependently

2012 ◽  
Vol 16 (2) ◽  
pp. 393-403 ◽  
Author(s):  
Alexia Polissidis ◽  
Andreas Galanopoulos ◽  
George Naxakis ◽  
Demetris Papahatjis ◽  
Zeta Papadopoulou-Daifoti ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Glutamate Release ◽  
Brain Regions ◽  
Cb1 Receptor ◽  
Glutamatergic Neurotransmission ◽  
Extracellular Dopamine ◽  
Cb1 Antagonist ◽  
Subcortical Regions ◽  
Underlying Mechanisms

Abstract Cannabinoid administration modulates both dopaminergic and glutamatergic neurotransmission. The present study examines the effects of high and low dose WIN55,212-2, a CB1 receptor agonist, on extracellular dopamine and glutamate release in vivo via brain microdialysis in the nucleus accumbens (NAc), striatum and prefrontal cortex (PFC) in parallel to its effects on locomotor activity. WIN55,212-2 increased extracellular dopamine in the NAc (1 mg/kg i.p.), striatum (0.1 and 1 mg/kg i.p.) and PFC (1 mg/kg i.p.). Glutamate release was also elevated by WIN55,212-2 in the PFC (1 mg/kg i.p.) whereas in the NAc (0.1 and 1 mg/kg i.p.) and striatum, it was reduced (1 mg/kg i.p.). WIN55,212-2 administration produced hyperlocomotion at the lower dose (0.1 mg/kg i.p.) and hypolocomotion at the higher dose (1 mg/kg i.p.). Co-administration with the CB1 antagonist, SR-141716A (0.03 mg/kg i.p.), prevented the above effects. According to the present results, WIN55,212-2 affected locomotor activity biphasically while exerting converging effects on dopamine activity but diverging effects on glutamate release between cortical and subcortical regions, especially at the higher dose. These findings emphasize the involvement of the CB1 receptor in the simultaneous modulation of dopaminergic and glutamatergic neurotransmission in brain regions involved in reward and locomotion and suggest possible underlying mechanisms of acute cannabinoid exposure and its psychoactive and behavioural manifestations.

scholarly journals Wireless, battery-free optoelectronic systems as subdermal implants for local tissue oximetry

2019 ◽  
Vol 5 (3) ◽  
pp. eaaw0873 ◽  
Author(s):  
Hao Zhang ◽  
Philipp Gutruf ◽  
Kathleen Meacham ◽  
Michael C. Montana ◽  
Xingyue Zhao ◽  
...  
Keyword(s):  
Animal Models ◽  
Tissue Oxygenation ◽  
Human Subjects ◽  
Brain Regions ◽  
Disease States ◽  
Data Output ◽  
Subdermal Implants ◽  
Underlying Mechanisms ◽  
Tissue Oximetry

Monitoring regional tissue oxygenation in animal models and potentially in human subjects can yield insights into the underlying mechanisms of local O2-mediated physiological processes and provide diagnostic and therapeutic guidance for relevant disease states. Existing technologies for tissue oxygenation assessments involve some combination of disadvantages in requirements for physical tethers, anesthetics, and special apparatus, often with confounding effects on the natural behaviors of test subjects. This work introduces an entirely wireless and fully implantable platform incorporating (i) microscale optoelectronics for continuous sensing of local hemoglobin dynamics and (ii) advanced designs in continuous, wireless power delivery and data output for tether-free operation. These features support in vivo, highly localized tissue oximetry at sites of interest, including deep brain regions of mice, on untethered, awake animal models. The results create many opportunities for studying various O2-mediated processes in naturally behaving subjects, with implications in biomedical research and clinical practice.

scholarly journals P62 accumulates through neuroanatomical circuits in response to tauopathy propagation

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
François-Xavier Blaudin de Thé ◽  
Benjamin Lassus ◽  
Ari W. Schaler ◽  
Stephanie L. Fowler ◽  
Chris N. Goulbourne ◽  
...  
Keyword(s):  
Disease Progression ◽  
Brain Regions ◽  
In Vitro Models ◽  
Tau Pathology ◽  
Neuron Models ◽  
Protein Clearance ◽  
Underlying Mechanisms ◽  
Tau Aggregation

AbstractIn Alzheimer’s disease and related tauopathies, trans-synaptic transfer and accumulation of pathological tau from donor to recipient neurons is thought to contribute to disease progression, but the underlying mechanisms are poorly understood. Using complementary in vivo and in vitro models, we examined the relationship between these two processes and neuronal clearance. Accumulation of p62 (a marker of defective protein clearance) correlated with pathological tau accumulation in two mouse models of tauopathy spread; Entorhinal Cortex-tau (EC-Tau) mice where tau pathology progresses in time from EC to other brain regions, and PS19 mice injected with tau seeds. In both models and in several brain regions, p62 colocalized with human tau in a pathological conformation (MC1 antibody). In EC-Tau mice, p62 accumulated before overt tau pathology had developed and was associated with the presence of aggregation-competent tau seeds identified using a FRET-based assay. Furthermore, p62 accumulated in the cytoplasm of neurons in the dentate gyrus of EC-Tau mice prior to the appearance of MC1 positive tauopathy. However, MC1 positive tau was shown to be present at the synapse and to colocalize with p62 as shown by immuno electron microscopy. In vitro, p62 colocalized with tau inclusions in two primary cortical neuron models of tau pathology. In a three-chamber microfluidic device containing neurons overexpressing fluorescent tau, seeding of tau in the donor chamber led to tau pathology spread and p62 accumulation in both the donor and the recipient chamber. Overall, these data are in accordance with the hypothesis that the accumulation and trans-synaptic spread of pathological tau disrupts clearance mechanisms, preceding the appearance of obvious tau aggregation. A vicious cycle of tau accumulation and clearance deficit would be expected to feed-forward and exacerbate disease progression across neuronal circuits in human tauopathies.

scholarly journals Normative brain size variation and brain shape diversity in humans

Science ◽  
2018 ◽  
Vol 360 (6394) ◽  
pp. 1222-1227 ◽  
Author(s):  
P. K. Reardon ◽  
Jakob Seidlitz ◽  
Simon Vandekar ◽  
Siyuan Liu ◽  
Raihaan Patel ◽  
...  
Keyword(s):  
Brain Size ◽  
Size Variation ◽  
Metabolic Cost ◽  
Brain Regions ◽  
Brain Organization ◽  
Neuroimaging Data ◽  
Subcortical Regions ◽  
Human Brains ◽  
Brain Shape

Brain size variation over primate evolution and human development is associated with shifts in the proportions of different brain regions. Individual brain size can vary almost twofold among typically developing humans, but the consequences of this for brain organization remain poorly understood. Using in vivo neuroimaging data from more than 3000 individuals, we find that larger human brains show greater areal expansion in distributed frontoparietal cortical networks and related subcortical regions than in limbic, sensory, and motor systems. This areal redistribution recapitulates cortical remodeling across evolution, manifests by early childhood in humans, and is linked to multiple markers of heightened metabolic cost and neuronal connectivity. Thus, human brain shape is systematically coupled to naturally occurring variations in brain size through a scaling map that integrates spatiotemporally diverse aspects of neurobiology.

Abnormalities in extracellular glycine and glutamate levels in the striatum of sandy mice

2013 ◽  
Vol 25 (4) ◽  
pp. 215-220
Author(s):  
Yuji Kitaichi ◽  
Ryota Hashimoto ◽  
Takeshi Inoue ◽  
Tomohiro Abekawa ◽  
Aya Kakuta ◽  
...  
Keyword(s):  
Amino Acids ◽  
Candidate Gene ◽  
Glutamate Release ◽  
Glutamatergic Neurotransmission ◽  
Wild Type ◽  
Extracellular Glutamate ◽  
Strong Candidate ◽  
The Relationship ◽  
Strong Candidate Gene

ObjectiveGlycine regulates glutamatergic neurotransmission, and several papers have reported the relationship between glycine and schizophrenia. The dysbindin-1 (DTNBP1: dystrobrevin-binding protein 1) gene is related to glutamatergic neurotransmission and has been found to be a strong candidate gene for schizophrenia. In this study, we clarified the relationship between dysbindin, glutamate, and glycine with in vivo microdialysis methods.MethodsWe measured extracellular glycine and glutamate levels in the striatum of sandy (sdy) mice using in vivo microdialysis methods. Sdy mice express no dysbindin protein owing to a deletion in the dysbindin-1 gene. In addition, we measured changes in those amino acids after methamphetamine (METH) administration.ResultsThe basal levels of extracellular glycine and glutamate in the striatum of sdy mice were elevated. These extracellular glutamate levels decreased gradually after METH administration and were not subsequently different from those of wild-type mice.ConclusionsThese results suggest that dysbindin might modulate glycine and glutamate release in vivo.

Hyperlocomotion during Recovery from Isoflurane Anesthesia Is Associated with Increased Dopamine Turnover in the Nucleus Accumbens and Striatum in Mice

1997 ◽  
Vol 86 (2) ◽  
pp. 464-475 ◽  
Author(s):  
Masahiro Irifune ◽  
Tomoaki Sato ◽  
Takashige Nishikawa ◽  
Takashi Masuyama ◽  
Masahiro Nomoto ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Nucleus Accumbens ◽  
High Performance ◽  
Gas Flow ◽  
Brain Regions ◽  
Dopamine Neurons ◽  
Dopamine Turnover

Background It was recently reported that isoflurane increases dopamine release in the striatum in rats both in vivo and in vitro, and that isoflurane inhibits uptake of dopamine in the rat brain synaptosomes. However, the functional role of these effects of isoflurane on dopamine neurons is uncertain. Dopaminergic mechanisms within the nucleus accumbens and striatum play an important role in the control of locomotor activity, and a change in dopamine turnover depends essentially on a change in impulse flow in the dopamine neurons. In this study, the effects of isoflurane on locomotor activity and on dopamine turnover were investigated in discrete brain regions in mice. Methods Mice were placed in individual airtight clear plastic chambers and spontaneously breathed isoflurane in 25% oxygen and 75% nitrogen (fresh gas flow, 4 l/min). Locomotor activity was measured with an Animex activity meter. Animals were decapitated after treatments with or without isoflurane, and the concentrations of monoamines and their metabolites in different brain areas were measured by high-performance liquid chromatography. Results During the 10 min after the cessation of the 20-min exposure to isoflurane, there was a significant increase in locomotor activity in animals breathing 1.5% isoflurane but not 0.7% isoflurane. This increase in locomotor activity produced by 1.5% isoflurane was abolished by a low dose of haloperidol (0.1 mg/kg), a dopamine receptor antagonist. Regional brain monoamine assays revealed that 1.5% isoflurane significantly increased the 3,4-dihydroxyphenylacetic acid:dopamine ratio (one indicator of transmitter turnover) in the nucleus accumbens and striatum, but a concentration of 0.7% did not. This significant increase in dopamine turnover in these regions continued during 20 min after the cessation of the administration of 1.5% isoflurane. Conclusions These results suggest that isoflurane-induced hyperlocomotion during emergence may be associated with increased dopamine turnover in the nucleus accumbens and striatum.

scholarly journals The Cerebral Metabolic Consequences of Nitric Oxide Synthase Deficiency: Glucose Utilization in Endothelial and Neuronal Nitric Oxide Synthase Null Mice

1999 ◽  
Vol 19 (2) ◽  
pp. 144-148 ◽  
Author(s):  
Susan E. Browne ◽  
Cenk Ayata ◽  
Paul L. Huang ◽  
Michael A. Moskowitz ◽  
M. Flint Beal
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Knockout Mice ◽  
Glucose Utilization ◽  
Brain Regions ◽  
In Vivo Autoradiography ◽  
Subcortical Regions ◽  
Oxide Synthase ◽  
The Brain

Nitric oxide has multiple physiologic roles in the CNS. Inhibiting nitric oxide synthesis might therefore alter functional activity within the brain. We used [14C]-2-deoxyglucose in vivo autoradiography to measure local CMRglc in “knockout” mice lacking the genes for either the endothelial (eNOS) or neuronal (nNOS) isoforms of nitric oxide synthase, and in the progenitor strains (SV129, CS7B1/6). Glucose utilization levels did not significantly differ between nNOS and eNOS knockout mice and C57B1/6 mice in any of the 48 brain regions examined, but were relatively lower in some subcortical regions in SV129 mice.

scholarly journals In Vivo Structural and Functional Abnormalities of the Striatums Is Related to Decreased Astrocytic BDNF in Itpr2-/- Mice Exhibiting Depressive-Like Behavior

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Shanmei Zeng ◽  
Kai Liu ◽  
Jingyu Zhang ◽  
Chunhui Chen ◽  
Yihua Xu ◽  
...  
Keyword(s):  
Gray Matter ◽  
Gray Matter Volume ◽  
Brain Regions ◽  
Specific Pattern ◽  
Brain Abnormalities ◽  
Matter Volume ◽  
Secondary Somatosensory Cortex ◽  
Underlying Mechanisms ◽  
The Right

Background. Previous researches indicate that Itpr2-/- mice (inositol 1,4,5-trisphosphate receptor type 2 knockout mice) show depressive-like symptoms; however, little is known regarding the in vivo neurobiological effect of Itpr2 as well as the specific pattern of brain abnormalities in Itpr2-/- mice. Methods/Materials. First, behavioral tests, structural magnetic resonance imaging (MRI), and resting-state functional MRI were performed on Itpr2-/- mice and matched healthy controls. Voxel-based morphometry and seed-based voxel-wise functional connectivity (FC) were, respectively, calculated to assess the gray matter volume and the functional activities of the brain in vivo. Second, the sample of relevant changed brain regions was extracted to detect the expression of BDNF. Finally, to further validate the relationship between Itpr2 deficiency and the observed brain abnormalities, we performed Western blotting to detect the expression of pro-BDNF and mBDNF in Itpr2-/- C8-D1A (a type of astrocyte). Results. Compared with controls, Itpr2-/- mice showed depressive-like behaviors as well as significantly lower gray matter volume in striatums mainly, periaqueductal GM, and the right frontoparietal cortices as well as lower striatal-hippocampal and striatal-right parietal cortex (mainly for the primary and secondary somatosensory cortex) FC. Moreover, decreased expression of mBDNF was found in both sample tissues of the striatum in Itpr2-/- mice and Itpr2-/- C8-D1A. Conclusion. By combining biochemistry and MR analyses, this study provides evidences to support that the Itpr2-related neuropathological effect is possibly mediated by the striatal abnormality associated with dysfunctional astrocytes in Itpr2-/- mice in vivo, thus may help us better understand underlying mechanisms of Itpr2 deficiency as well as its relation to depressive-like behavior.

scholarly journals Quantification of the Cannabinoid Type 1 Receptor Availability in the Mouse Brain

2020 ◽  
Vol 14 ◽  
Author(s):  
Isabelle Miederer ◽  
Viktoria Wiegand ◽  
Nicole Bausbacher ◽  
Petra Leukel ◽  
Stephan Maus ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Mouse Brain ◽  
Brain Regions ◽  
Cb1 Receptor ◽  
Receptor Ligand ◽  
Addictive Disorders ◽  
Cannabinoid Type 1 Receptor ◽  
Slow Kinetics

Introduction: The endocannabinoid system is involved in several diseases such as addictive disorders, schizophrenia, post-traumatic stress disorder, and eating disorders. As often mice are used as the preferred animal model in translational research, in particular when using genetically modified mice, this study aimed to provide a systematic analysis of in vivo cannabinoid type 1 (CB1) receptor ligand-binding capacity using positron emission tomography (PET) using the ligand [18F]MK-9470. We then compared the PET results with literature data from immunohistochemistry (IHC) to review the consistency between ex vivo protein expression and in vivo ligand binding.Methods: Six male C57BL/6J (6–9 weeks) mice were examined with the CB1 receptor ligand [18F]MK-9470 and small animal PET. Different brain regions were evaluated using the parameter %ID/ml. The PET results of the [18F]MK-9470 accumulation in the mouse brain were compared with immunohistochemical literature data.Results: The ligand [18F]MK-9470 was taken up into the mouse brain within 5 min after injection and exhibited slow kinetics. It accumulated highly in most parts of the brain. PET and IHC classifications were consistent for most parts of the telencephalon, while brain regions of the diencephalon, mesencephalon, and rhombencephalon were rated higher with PET than IHC.Conclusions: This preclinical [18F]MK-9470 study demonstrated the radioligand’s applicability for imaging the region-specific CB1 receptor availability in the healthy adult mouse brain and thus offers the potential to study CB1 receptor availability in pathological conditions.

scholarly journals What Do Language Disorders Reveal about Brain–Language Relationships? From Classic Models to Network Approaches

2017 ◽  
Vol 23 (9-10) ◽  
pp. 741-754 ◽  
Author(s):  
Nina F. Dronkers ◽  
Maria V. Ivanova ◽  
Juliana V. Baldo
Keyword(s):  
Language Processing ◽  
Brain Injuries ◽  
Brain Activity ◽  
Language Disorders ◽  
Brain Regions ◽  
Language Functions ◽  
Subcortical Regions ◽  
Communication Impairments ◽  
The Brain

AbstractStudies of language disorders have shaped our understanding of brain–language relationships over the last two centuries. This article provides a review of this research and how our thinking has changed over the years regarding how the brain processes language. In the 19th century, a series of famous case studies linked distinct speech and language functions to specific portions of the left hemisphere of the brain, regions that later came to be known as Broca’s and Wernicke’s areas. One hundred years later, the emergence of new brain imaging tools allowed for the visualization of brain injuriesin vivothat ushered in a new era of brain-behavior research and greatly expanded our understanding of the neural processes of language. Toward the end of the 20th century, sophisticated neuroimaging approaches allowed for the visualization of both structural and functional brain activity associated with language processing in both healthy individuals and in those with language disturbance. More recently, language is thought to be mediated by a much broader expanse of neural networks that covers a large number of cortical and subcortical regions and their interconnecting fiber pathways. Injury to both grey and white matter has been seen to affect the complexities of language in unique ways that have altered how we think about brain–language relationships. The findings that support this paradigm shift are described here along with the methodologies that helped to discover them, with some final thoughts on future directions, techniques, and treatment interventions for those with communication impairments. (JINS, 2017,23, 741–754)

scholarly journals Neurochemical and Behavioral Effects of a New Hallucinogenic Compound 25B-NBOMe in Rats

2020 ◽  
Author(s):  
Adam Wojtas ◽  
Monika Herian ◽  
Mateusz Skawski ◽  
Małgorzata Sobocińska ◽  
Alejandro González-Marín ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Comet Assay ◽  
Short Term Memory ◽  
Glutamate Release ◽  
Anxiolytic Effect ◽  
Brain Regions ◽  
The Novel ◽  
Object Recognition Test ◽  
Wide Range ◽  
Dose Dependent

Abstract4-Bromo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25B-NBOMe) is a hallucinogen exhibiting high binding affinity for 5-HT2A/C serotonin receptors. In the present work, we investigated its effect on dopamine (DA), serotonin (5-HT), acetylcholine (ACh), and glutamate release in the rat frontal cortex, striatum, and nucleus accumbens. Hallucinogenic activity, impact on cognitive and motor functions, and anxiogenic/anxiolytic properties of this compound were also tested. The release of DA, 5-HT, ACh, and glutamate was studied using microdialysis in freely moving animals. Hallucinogenic activity was investigated using head and body twitch response (WDS), cognitive functions were examined with the novel object recognition test (NOR), locomotor activity was studied in the open field (OF), while anxiogenic/anxiolytic effect was tested using the light/dark box (LDB). Neurotoxicity was evaluated with the comet assay. 25B-NBOMe increased DA, 5-HT, and glutamate release in all studied brain regions, induced hallucinogenic activity, and lowered the recognition index (Ri) vs. control in the NOR test. It also decreased locomotor activity of rats in the OF test. The effect of 25B-NBOMe in the NOR test was inhibited by scopolamine. In the LDB test, the time spent in the dark zone was longer in comparison to control and was dose-dependent. In contrast to MDMA, 25B-NBOMe showed subtle genotoxic effect observed in the comet assay.Our findings indicate that 25B-NBOMe shows hallucinogenic activity in the wide range of doses. The changes in neurotransmitter levels may be related to 25B-NBOMe affinity for 5-HT2A receptor. Alterations in the NOR, OF, and LDB indicate that 25B-NBOMe impacts short-term memory, locomotion, and may be anxiogenic.

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