| 1. |
- Atis, Muge, et al.
(författare)
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Targeting the blood-brain barrier disruption in hypertension by ALK5/ TGF-? : type I receptor inhibitor SB-431542 and dynamin inhibitor dynasore
- 2022
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Ingår i: Brain Research. - : Elsevier. - 0006-8993 .- 1872-6240. ; 1794
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: In this study, we aimed to target two molecules, transforming growth factor-beta (TGF-beta) and dynamin to explore their roles in blood-brain barrier (BBB) disruption in hypertension. Methods: For this purpose, angiotensin (ANG) II-induced hypertensive mice were treated with SB-431542, an inhibitor of the ALK5/TGF-beta type I receptor, and dynasore, an inhibitor of dynamin. Albumin-Alexa fluor 594 was used to assess BBB permeability. The alterations in the expression of claudin-5, caveolin (Cav)-1, glucose transporter (Glut)-1, and SMAD4 in the cerebral cortex and the hippocampus were evaluated by quantification of immunofluorescence staining intensity.Results: ANG II infusion increased BBB permeability to albumin-Alexa fluor 594 which was reduced by SB431542 (P < 0.01), but not by dynasore. In hypertensive animals treated with dynasore, claudin-5 immunofluorescence intensity increased in the cerebral cortex and hippocampus while it decreased in the cerebral cortex of SB-431542 treated hypertensive mice (P < 0.01). Both dynasore and SB-431542 prevented the increased Cav-1 immunofluorescence intensity in the cerebral cortex and hippocampus of hypertensive animals (P < 0.01). SB431542 and dynasore decreased Glut-1 immunofluorescence intensity in the cerebral cortex and hippocampus of mice receiving ANG II (P < 0.01). SB-431542 increased SMAD4 immunofluorescence intensity in the cerebral cortex of hypertensive animals, while in the hippocampus a significant decrease was noted by both SB-431542 and dynasore (P < 0.01).Conclusion: Our data suggest that inhibition of the TGF beta type I receptor prevents BBB disruption under hypertensive conditions. These results emphasize the therapeutic potential of targeting TGF beta signaling as a novel treatment modality to protect the brain of hypertensive patients.
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| 2. |
- Bay, V., et al.
(författare)
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Flinders sensitive line rats are resistant to infarction following transient occlusion of the middle cerebral artery
- 2020
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993. ; 1737
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Tidskriftsartikel (refereegranskat)abstract
- Background: Depression is a common complication of stroke and increases the risk of mortality and disability. Pre-stroke depression is a possible risk factor for stroke and has also been linked to adverse outcomes. The underlying mechanisms linking depression and stroke remain unclear. Preclinical models may provide novel insights, but models reflecting both conditions are lacking. Methods: In this study, we investigated the effects of a 45-min transient middle cerebral artery occlusion (MCAo) on infarct size in male adult Flinders Sensitive Line rats, a genetic animal model of depression, and their control strains Flinders Resistant Line and Sprague-Dawley rats. Infarct size was assessed by tetrazolium chloride (TTC) and microtubule-associated protein 2 (MAP2) staining after 48 h of reperfusion. Angiograms of the vascular structure of naive animals were produced with a mu-CT scanner. Results: Both Flinders strains had significantly smaller infarcts following MCAo compared to Sprague-Dawley rats. This effect does not appear to be due to changes in cerebrovascular architecture, as indicated by an initial exploration of vascular organization using angiograms, or body temperature regulation. Conclusions: Our study suggests that the rat strain does not influence infarct volumes following MCAo.
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| 3. |
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| 4. |
- Brown, Kyle A., et al.
(författare)
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Lacto-N-fucopentaose-III (LNFPIII) ameliorates acute aberrations in hippocampal synaptic transmission in a Gulf War Illness animal model
- 2021
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Ingår i: Brain Research. - : Elsevier. - 0006-8993 .- 1872-6240. ; 1766
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Tidskriftsartikel (refereegranskat)abstract
- Approximately one-third of Persian Gulf War veterans are afflicted by Gulf War Illness (GWI), a chronic multisymptom condition that fundamentally presents with cognitive deficits (i.e., learning and memory impairments) and neuroimmune dysfunction (i.e., inflammation). Factors associated with GWI include overexposures to neurotoxic pesticides and nerve agent prophylactics such as permethrin (PM) and pyridostigmine bromide (PB), respectively. GWI-related neurological impairments associated with PB-PM overexposures have been recapitulated in animal models; however, there is a paucity of studies assessing PB-PM-related aberrations in hippocampal synaptic plasticity and transmission that may underlie behavioral impairments. Importantly, FDA-approved neuroactive treatments are currently unavailable for GWI. In the present study, we assessed the efficacy of an immunomodulatory therapeutic, lacto-N-fucopentaose-III (LNFPIII), on ameliorating acute effects of in vivo PB-PM exposure on synaptic plasticity and transmission as well as trophic factor/cytokine expression along the hippocampal dorsoventral axis. PB-PM exposure resulted in hippocampal synaptic transmission deficits 48 h post-exposure, a response that was ameliorated by LNFPIII coadministration, particularly in the dorsal hippocampus (dH). LNFPIII coadministration also enhanced synaptic transmission in the dH and the ventral hippocampus (vH). Notably, LNFPIII coadministration elevated long-term potentiation in the dH. Further, PB-PM exposure and LNFPIII coadministration uniquely altered key inflammatory cytokine and trophic factor production in the dH and the vH. Collectively, these findings demonstrate that PB-PM exposure impaired hippocampal synaptic responses 48 h post-exposure, impairments that differentially manifested along the dorsoventral axis. Importantly, LNFPIII ameliorated GWI-related electrophysiological deficits, a beneficial effect indicating the potential efficacy of LNFPIII for treating GWI.
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| 5. |
- Bruschettini, Matteo, et al.
(författare)
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The effects of caffeine following hypoxic-ischemic encephalopathy : A systematic review of animal studies
- 2022
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Ingår i: Brain Research. - : Elsevier BV. - 1872-6240 .- 0006-8993. ; 1790
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Caffeine is believed to be neuroprotective in preterm and term infants, despite the conflicting data on its effects on the developing brain in animal models. We aimed to conduct a systematic review with meta-analysis assessing the effects of caffeine on the prevention and treatment of neurological morbidity caused by hypoxic-ischemic encephalopathy (HIE) in preclinical studies.METHODS: Randomized and non-randomized control studies in animal models of HIE reporting caffeine administration within the first ten days of life were included. Primary outcomes were behavioral tests that served as surrogates for cognition, memory, motor coordination, and gait; secondary outcomes pertained to structural neurologic changes. Screening for inclusion, risk of bias and data extraction were performed independently by two authors.RESULTS: Seven studies met inclusion: 5 studies were conducted in rats and 2 in mice. All studies were performed in full-term animals, and the majority of studies used animals of both sexes (5/7). In six studies, caffeine was administered intraperitoneally to the pups, while in the remaining study, it was delivered via the drinking water of the lactating dams. The doses of caffeine ranged from 5 to 20 mg/kg; in one study, caffeine dosage was 0.3 mg/L in the drinking water of lactating dam. The mortality rate was reported only in three studies. Caffeine had a positive effect on overall functional outcome (SDM 0.92(95%CI 0.25 to 1.59)). Animals treated with caffeine performed better on Morris water maze and rotarod tests (SDM -1.39(95%CI -0.36 to -2.41)) and (SDM 1.03(95%CI 0.03 to 2.04)), respectively. Caffeine treated animals performed worse on open field test compared to the controls (SDM -1.11(95%CI -3.01 to 0.80)). The overall quality of the included studies was limited.CONCLUSIONS: Early caffeine exposure in preclinical rodent models of HIE is associated with improved selective functional and neurological outcomes, although the certainty of the evidence is limited. To validate the therapeutic efficacy of caffeine as a neuroprotective adjuvant, there is a need to explore its effects in larger animal models, which will help guide the design of relevant clinical trials.
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| 6. |
- Eide, P. K., et al.
(författare)
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Blood-brain barrier leakage of blood proteins in idiopathic normal pressure hydrocephalus
- 2020
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993. ; 1727
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Idiopathic normal pressure hydrocephalus (iNPH) is one subtype of dementia characterized by cerebrospinal fluid (CSF) disturbance, but with unknown cause. We recently reported that frontal cortex biopsies of iNPH patients disclosed degenerative alterations of the capillary basement membrane, including degenerated pericyte processes. Given that pericyte degeneration is associated with blood-brain barrier (BBB) dysfunction, the present study was undertaken to examine whether BBB leakage of blood proteins can be revealed by light microscopy (LM) immunohistochemistry in iNPH. Methods: The study included cortical brain tissue specimens from 14 reference (REF) subjects undergoing neurosurgery for epilepsy, aneurysm or tumor, and 45 iNPH patients. Dysfunction of the BBB was measured semi-quantitatively as area percentage extravasated fibrin(ogen) in cerebral cortical layers I, II and III. The degree of fibrin(ogen) extravasation was also correlated with expression of glial fibrillary acidic protein (GFAP), aquaporin-4 (AQP4), dystrophin 71 (Dp71) and Cluster of Differentiation 68 (CD68). Results: The study disclosed extravasation of fibrin(ogen) in 4/14 REF subjects and in 45/45 iNPH patients, the percentage area of fibrin(ogen) was significantly higher in iNPH than REF cortical specimens. Diffuse, less prominent fibrin(ogen) extravasation was seen in the subcortical white matter of one iNPH individual. Increasing degree of fibrinogen extravasation in cerebral cortex was significantly associated with increasing degree of astrogliosis and with reduced expression of perivascular AQP4 and Dp71. Conclusions: The present results provide evidence of BBB dysfunction in iNPH. The BBB leakage of blood proteins may render for impaired neurovascular units in iNPH patients.
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| 7. |
- Furubacke, Amanda, et al.
(författare)
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Alternating dual-task interference between visual words and faces
- 2020
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Ingår i: Brain Research. - : ELSEVIER. - 0006-8993 .- 1872-6240. ; 1746
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Tidskriftsartikel (refereegranskat)abstract
- The many-to-many hypothesis proposes that face and visual word recognition share and even compete for high-level perceptual resources in both hemispheres. However, it is still not clear whether the processing performed by the two hemispheres on faces and visual words is equivalent or complementary. We performed an alternating dual-task experiment to determine if the processing of visual words and faces interfered with each other, and if such interference depended upon the stimulus attribute being processed. Subjects saw a series of alternating stimuli and made same-different judgments comparing the current stimulus with the one two trials before. In some blocks faces or visual words alternated with colored gratings, in other blocks they alternated between different sets of words or different sets of faces. In the key experimental blocks they alternated between visual words and faces. Subjects were also asked to focus on different properties of the stimuli (identity or speech sounds for faces, handwriting or word content for visual words, color or orientation for gratings). There was no evidence of specific interference when subjects alternated between face and word attributes thought to be processed by opposite hemispheres (e.g. face identity and word identity, facial speech and handwriting). Rather interference occurred when subjects alternated between attributes that may be processed by the same hemisphere. The results support a modified version of the many-to-many hypothesis which takes into account complementary functions of the left and the right hemispheres in the processing of faces and visual words.
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| 8. |
- Gosselke Berthelsen, Sabine, et al.
(författare)
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Different neural mechanisms for rapid acquisition of words with grammatical tone in learners from tonal and non-tonal backgrounds : ERP evidence
- 2020
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993. ; 1729
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Tidskriftsartikel (refereegranskat)abstract
- Initial second language acquisition proceeds surprisingly quickly. Foreign words can sometimes be used within minutes after the first exposure. Yet, it is unclear whether such rapid learning also takes place for more complex, multi-layered properties like words with complex morphosyntax and/or tonal features, and whether it is influenced by transfer from the learners’ native language. To address these questions, we recorded tonal and non-tonal learners’ brain responses while they acquired novel tonal words with grammatical gender and number on two consecutive days. Comparing the novel words to repeated but non-taught pseudoword controls, we found that tonal learners demonstrated a full range of early and late event-related potentials in novel tonal word processing: an early word recognition component (~50 ms), an early left anterior negativity (ELAN), a left anterior negativity (LAN), and a P600. Non-tonal learners exhibited mainly late processing when accessing the meaning of the tonal words: a P600, as well as a LAN after an overnight consolidation. Yet, this group displayed correlations between pitch perception abilities and ELAN, and between acquisition accuracy and LAN, suggesting that certain features may lead to facilitated processing of tonal words in non-tonal learners. Furthermore, the two groups displayed indistinguishable performance at the behavioural level, clearly suggesting that the same learning outcome may be achieved through at least partially different neural mechanisms. Overall, the results suggest that it is possible to rapidly acquire words with grammatical tone and that transfer plays an important role even in very early second language acquisition.
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| 9. |
- Guillaumin, Adriane, et al.
(författare)
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Experimental investigation into the role of the subthalamic nucleus (STN) in motor control using optogenetics in mice
- 2021
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Ingår i: Brain Research. - : Elsevier. - 0006-8993 .- 1872-6240. ; 1755
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Tidskriftsartikel (refereegranskat)abstract
- The subthalamic nucleus (STN) is critical for the execution of intended movements. Loss of its normal function is strongly associated with several movement disorders, including Parkinson's disease for which the STN is an important target area in deep brain stimulation (DBS) therapy. Classical basal ganglia models postulate that two parallel pathways, the direct and indirect pathways, exert opposing control over movement, with the STN acting within the indirect pathway. The STN is regulated by both inhibitory and excitatory input, and is itself excitatory. While most functional knowledge of this clinically relevant brain structure has been gained from pathological conditions and models, primarily parkinsonian, experimental evidence for its role in normal motor control has remained more sparse. The objective here was to tease out the selective impact of the STN on several motor parameters required to achieve intended movement, including locomotion, balance and motor coordination. Optogenetic excitation and inhibition using both bilateral and unilateral stimulations of the STN were implemented in freely-moving mice. The results demonstrate that selective optogenetic inhibition of the STN enhances locomotion while its excitation reduces locomotion. These findings lend experimental support to basal ganglia models of the STN in terms of locomotion. In addition, optogenetic excitation in freely-exploring mice induced self-grooming, disturbed gait and a jumping/escaping behavior, while causing reduced motor coordination in advanced motor tasks, independent of grooming and jumping. This study contributes experimentally validated evidence for a regulatory role of the STN in several aspects of motor control.
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| 10. |
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| 11. |
- Iida, Takashi, et al.
(författare)
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Plasticity in corticomotor pathways linked to a jaw protrusion training task : Potential implications for management of patients with obstructive sleep apnea.
- 2020
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Ingår i: Brain Research. - : Elsevier. - 0006-8993 .- 1872-6240. ; 1749
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated the effect of a repeated and standardized jaw protrusion training (JPT) task on corticomotor excitability as assessed by motor evoked potentials (MEPs) in masseter and tongue muscle with the use of transcranial magnetic stimulation (TMS). Sixteen healthy participants performed three series of a standardized JPT task on three consecutive days. Each day participants performed 41-min of JPT consisting of three series. In all series, participants were instructed to target 50% and 100% of the maximum jaw protrusion positions. In the first and third series without any feedback but during the second series, participants were provided a custom-made mandibular advancement device to help achieve the correct protruded position. Single pulse TMS was applied to elicit MEPs from right masseter, right tongue and right first dorsal interosseous muscles (FDI) (as control), pre and post-task on Day-1 and -3. Masseter MEPs and tongue MEPs were significantly dependent on stimulus intensity (P < 0.001) and on task session (P < 0.001). Amplitude of masseter and tongue MEPs at post-task Day-3 were significantly higher compared to baseline values (pre-task Day-1) (P < 0.005). FDI MEPs were dependent on stimulus intensity only (P < 0.001) but not on task session (P = 0.677). Our novel findings suggest that participants performing an active and repeated JPT task demonstrate neuroplasticity in terms of increased corticomotor excitability not only in masseter muscles but also in tongue muscles. This finding may have implications for patients with obstructive sleep apnea treated by a mandibular advancement device where the lower jaw is passively held in a protruded position.
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| 12. |
- Jerlhag, Elisabeth, 1978
(författare)
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Alcohol-mediated behaviours and the gut-brain axis; with focus on glucagon-like peptide-1
- 2020
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993. ; 1727
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Forskningsöversikt (refereegranskat)abstract
- The neurochemical mechanisms that regulate development of alcohol use disorder (AUD) are complex, and gut-brain peptides were recently pinpointed as novel modulators. Gut-brain peptides, such as glucagon-like peptide-1 (GLP-1), are well known for their ability to regulate food intake and appetite. GLP-1 also controls glucose homeostasis, which lead to the approval of GLP-1 receptor agonists for treatment of diabetes type II. These pharmacotherapies, including exenatide/exendin-4(Ex4) and liraglutide, have also been tested in various animal modes of AUD. In mice, Ex4 attenuates the acute behavioural responses to alcohol. Rat studies additionally show that Ex4 reduces the intake and the intravenous operant self-administration of alcohol and decreases the motivation to consume alcohol. Further studies established that Ex4 modulates alcohol-mediated behaviours via activation of GLP-1 receptors in reward related areas and an area of the hindbrain. In rodents, liraglutide reduces withdrawal symptoms of alcohol, prevents acute alcohol to activate the mesolimbic dopamine system, and in turn reduces various alcohol drinking behaviours. Supportively, liraglutide decreases alcohol intake in vervet monkeys. Finally, another GLP-1 receptor agonist, AC3174, counteracts relapse drinking to alcohol. Of clinical relevance is the case-control study which reveals associations between polymorphisms in the GLP-1 receptor gene and AUD. Furthermore, a polymorphism in the GLP-1 receptor gene is associated with enhanced intravenous self-administration of alcohol in social drinkers and higher response in globus pallidus following high monetary reward. Collectively, these data provide evidence that up-coming clinical trials should evaluate the effect of these GLP-1 receptor agonists on alcohol intake in patients with AUD.
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| 13. |
- Mao, Haian, et al.
(författare)
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Increase of vesicular glutamate transporter 2 co-expression in the deep cerebellar nuclei related to skilled reach learning
- 2022
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Ingår i: Brain Research. - : Elsevier. - 0006-8993 .- 1872-6240. ; 1782
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Tidskriftsartikel (refereegranskat)abstract
- Motor learning induces plasticity in multiple brain regions involving the cerebellum as a crucial player. Synaptic plasticity in the excitatory collaterals to the cerebellar output, the deep cerebellar nuclei (DCN), have recently been shown to be an important part of motor learning. These synapses are composed of climbing fiber (CF) and mossy fiber synapses, with the former conveying unconditioned and the latter conditioned responses in classical conditioning paradigms. The CF synapse on to the cerebellar cortex and the DCN express vesicular transporter 2 (vGluT2), whereas mossy fibers express vGluT1 and /or vGluT2 in their terminals. However, the underlying regulatory mechanism of vGluT expression in the DCN remains unknown. Here we confirm the increase of vGluT2 in a specific part of the DCN during the acquisition of a skilled reaching task in mice. Furthermore, our findings show that this is due to an increase in co-expression of vGluT2 in vGluT1 presynapses instead of the formation of new vGluT2 synapses. Our data indicate that remodeling of synapses – in contrast to synaptogenesis - also plays an important role in motor learning and may explain the presence of both vGluT's in some mossy fiber synapses.
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| 14. |
- Marinkovic, I., et al.
(författare)
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A basic MRI anatomy of the rat brain in coronal sections for practical guidance to neuroscientists
- 2020
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993. ; 1747
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Tidskriftsartikel (refereegranskat)abstract
- Identification of the brain structures in the magnetic resonance imaging (MRI) of the rat is very important for the experimental work of many neuroscientists. Our intention was to recognize most of the structures without overlapping the MRI sections with the histological templates. Three live rats were used for this study who were examined in a micro-MRI apparatus by performing T2-weighted sequences in serial brain sections. Most of the white matter structures were easily identified, e.g. the anterior commissure, corpus callosum with forceps minor and major, cingulum, external and internal capsules, fornix, stria medullaris and terminalis, cranial nerves, mammillothalamic tract, fasciculus retroflexus, medial and lateral lemniscus, posterior commissure, commissures of the superior and inferior colliculi, medial longitudinal fasciculus, and the cerebral peduncle. Large and small gray matter structures were recognized as well, for example, the anterior olfactory structures, nucleus accumbens, caudate putamen, claustrum, bed nucleus of the stria terminalis, pituitary gland, globus pallidus, amygdala, some midline and intralaminar thalamic nuclei, certain hypothalamic nuclei, hippocampal formation, pineal body, periaqueductal gray matter, lateral and medial geniculate bodies, superior and inferior colliculi, and cranial nerves nuclei. All in all, of the total 160 recognized brain structures, 77 were identified without using the corresponding histological atlases. We believe that our labeled MRI pictures could be an important way for quick orientation for evaluating the effects of the experimental work regarding the rat brain.
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| 15. |
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| 16. |
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| 17. |
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| 18. |
- Novén, Mikael, et al.
(författare)
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Cortical thickness and surface area of left anterior temporal areas affects processing of phonological cues to morphosyntax
- 2021
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993. ; 1750
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Tidskriftsartikel (refereegranskat)abstract
- Lack of methods to experimentally assess the perceptual processing of sound features and allow one to measure differences in phonological proficiency has been a limitation for speech processing studies in native speakers. Tonal features associated with Swedish word-stems, word accents, which cue grammatical suffixes, constitute, however, such sound features that can be exploited to generate measures of reliance on morphosyntactically relevant phonological information during word processing. Specifically, there is a natural variance between native speakers in response time (RT) difference between phonologically valid and invalid word accent-suffix combinations that can be used to quantify perceptual phonological proficiency. This study uses ultra-high field magnetic resonance imaging (MRI) to investigate word accents as phonological cues to morphosyntactic meaning. The study adds to the understanding of the neural basis for both morphosyntactically relevant phonological cues by reporting correlations between differences in listeners’ RT for validly and invalidly cued suffixes and cortical thickness in left anterior and middle temporal gyrus, and the left anterior superior temporal sulcus as well as cortical surface area in the left middle and inferior temporal gyri. The cortical areas studied are known constituents of the ventral speech processing stream, necessary for word and phrase recognition.
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| 19. |
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| 20. |
- Titulaer, Joep, et al.
(författare)
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Sex-specific differences and similarities of olanzapine and risperidone on avoidance suppression in rats in the conditioned avoidance response test
- 2023
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993 .- 1872-6240. ; 1818
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Tidskriftsartikel (refereegranskat)abstract
- It is well known that antipsychotic drugs (APDs) are more effective in reducing symptoms in women than in men, and that women are more sensitive to the side effects of APDs. Therefore, it is of great importance that sex differences in drug responses are considered already in the early stages of drug development. In this study, we investigated whether sex-specific differences could be observed in response to the commonly prescribed APDs olanzapine and risperidone using the conditioned avoidance response (CAR) test. To this end we tested the effect of 1.25 and 2.5 mg/kg olanzapine and 0.25 and 0.4 mg/kg risperidone using female and male Wistar rats in the CAR test. Whereas there were no significant differences between the female and male rats in response to either dose of olanzapine administration, an injection of 0.4 mg/kg risperidone significantly suppressed avoidance more in female rats than in male rats. In addition, we found that the estrous cycle of the female rats did not have a significant effect on the avoidance response. In conclusion, we show that there are sex-specific differences as well as similarities between female and male rats in the CAR test and novel APDs should be tested on female and male rats in the future.
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| 21. |
- Viaro, Riccardo, et al.
(författare)
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L-DOPA promotes striatal dopamine release through D1 receptors and reversal of dopamine transporter
- 2021
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Ingår i: BRAIN RESEARCH. - : Elsevier BV. - 0006-8993 .- 1872-6240. ; 1768
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have pointed out that L-DOPA can interact with D1 or D2 receptors independent of its conversion to endogenous dopamine. The present study was set to investigate whether L-DOPA modulates dopamine release from striatal nerve terminals, using a preparation of synaptosomes preloaded with [3H]DA. Levodopa (1 mu M) doubled the K+-induced [3H]DA release whereas the D2/D3 receptor agonist pramipexole (100 nM) inhibited it. The L-DOPA-evoked facilitation was mimicked by the D1 receptor agonist SKF38393 (30-300 nM) and prevented by the D1/D5 antagonist SCH23390 (100 nM) but not the DA transporter inhibitor GBR12783 (300 nM) or the aromatic L-amino acid decarboxylase inhibitor benserazide (1 mu M). Higher L-DOPA concentrations (10 and 100 mu M) elevated spontaneous [3H]DA efflux. This effect was counteracted by GBR12783 but not SCH23390. Binding of [3H]SCH23390 in synaptosomes (in test tubes) revealed a dense population of D1 receptors (2105 fmol/mg protein). Both SCH23390 and SKF38393 fully inhibited [3H]SCH23390 binding (Ki 0.42 nM and 29 nM, respectively). L-DOPA displaced [3H]SCH23390 binding maximally by 44% at 1 mM. This effect was halved by addition of GBR12935 and benserazide. We conclude that L-DOPA facilitates exocytotic [3H]DA release through SCH23390-sensitive D1 receptors, independent of its conversion to DA. It also promotes non-exocytotic [3H]DA release, possibly via conversion to DA and reversal of DA transporter. These data confirm that L-DOPA can directly interact with dopamine D1 receptors and might extend our knowledge of the neurobiological mechanisms underlying L-DOPA clinical effects.
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| 22. |
- Zamorano, A. M., et al.
(författare)
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Singing training predicts increased insula connectivity with speech and respiratory sensorimotor areas at rest
- 2023
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993 .- 1872-6240. ; 1813
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Tidskriftsartikel (refereegranskat)abstract
- The insula contributes to the detection of salient events during goal-directed behavior and participates in the coordination of motor, multisensory, and cognitive systems. Recent task-fMRI studies with trained singers sug-gest that singing experience can enhance the access to these resources. However, the long-term effects of vocal training on insula-based networks are still unknown. In this study, we employed resting-state fMRI to assess experience-dependent differences in insula co-activation patterns between conservatory-trained singers and non-singers. Results indicate enhanced bilateral anterior insula connectivity in singers relative to non-singers with constituents of the speech sensorimotor network. Specifically, with the cerebellum (lobule V-VI) and the superior parietal lobes. The reversed comparison showed no effects. The amount of accumulated singing training pre-dicted enhanced bilateral insula co-activation with primary sensorimotor areas representing the diaphragm and the larynx/phonation area-crucial regions for cortico-motor control of complex vocalizations-as well as the bilateral thalamus and the left putamen. Together, these findings highlight the neuroplastic effect of expert singing training on insula-based networks, as evidenced by the association between enhanced insula co-activation profiles in singers and the brain's speech motor system components.
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