The Experts below are selected from a list of 39 Experts worldwide ranked by ideXlab platform
Christopher A Salvatore - One of the best experts on this subject based on the ideXlab platform.
-
localization of cgrp receptor components and receptor binding sites in rhesus monkey brainstem a detailed study using in situ hybridization immunofluorescence and autoradiography
The Journal of Comparative Neurology, 2016Co-Authors: Sajedeh Eftekhari, Renee C Gaspar, Rhonda Roberts, Tsingbau Chen, Zhizhen Zeng, Stephanie Villarreal, Lars Edvinsson, Christopher A SalvatoreAbstract:Functional imaging studies have revealed that certain brainstem areas are activated during migraine attacks. The neuropeptide calcitonin gene-related peptide (CGRP) is associated with activation of the trigeminovascular system, transmission of nociceptive information and plays a key role in migraine pathophysiology. Therefore, to elucidate the role of CGRP it is critical to identify the regions within the brainstem that processes CGRP signaling. In situ hybridization and immunofluorescence were performed to detect mRNA expression and define cellular localization of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1), respectively. To define CGRP receptor binding sites, in vitro autoradiography was performed with [(3) H]MK-3207 (a CGRP receptor antagonist). CLR and RAMP1 mRNA and protein expression were detected in the pineal gland, medial mammillary Nucleus, median eminence, infundibular stem, periaqueductal gray, area postrema, Pontine Raphe Nucleus, gracile Nucleus and spinal trigeminal Nucleus and the spinal cord. RAMP1 mRNA expression was also detected in the posterior hypothalamic area, trochlear Nucleus, dorsal Raphe Nucleus, medial lemniscus, Pontine nuclei, vagus nerve, inferior olive, abducens Nucleus, motor trigeminal Nucleus; where protein co-expression of CLR and RAMP1 was observed via immunofluorescence. [(3) H]MK-3207 showed high binding densities concordant with mRNA and protein expression. The present study suggests that several regions in the brainstem may be involved in CGRP signaling. Interestingly, we found receptor expression and antagonist binding in some areas that are not protected by the blood-brain barrier, which suggests that CGRP receptor antagonists may not need to be CNS-penetrant to antagonize receptors in these brain regions. This article is protected by copyright. All rights reserved. (Less)
Andrew L Gundlach - One of the best experts on this subject based on the ideXlab platform.
-
relaxin 3 innervation of the intergeniculate leaflet of the rat thalamus neuronal tract tracing and in vitro electrophysiological studies
European Journal of Neuroscience, 2013Co-Authors: Anna Blasiak, John D. Wade, Andrew L Gundlach, Tomasz Blasiak, M H Lewandowski, Mohammed Akhter HossainAbstract:Behavioural state is controlled by a range of neural systems that are sensitive to internal and external stimuli. The relaxin-3 and relaxin family peptide receptor 3 (RXFP3) system has emerged as a putative ascending arousal network with putative involvement in regulation of stress responses, neuroendocrine control, feeding and metabolism, circadian activity and cognition. Relaxin-3/γ-aminobutyric acid neuron populations have been identified in the Nucleus incertus, Pontine Raphe Nucleus, periaqueductal grey (PAG) and an area dorsal to the substantia nigra. Relaxin-3-positive fibres/terminals densely innervate arousal-related structures in the brainstem, hypothalamus and limbic forebrain, but the functional significance of the heterogeneous relaxin-3 neuron distribution and its inputs to specific brain areas are unclear. Therefore, in this study, we used neuronal tract-tracing and immunofluorescence staining to explore the source of the dense relaxin-3 innervation of the intergeniculate leaflet (IGL) of the thalamus, a component of the neural circadian timing system. Confocal microscopy analysis revealed that relaxin-3-positive neurons retrogradely labelled from the IGL were predominantly present in the PAG and these neurons expressed corticotropin-releasing factor receptor-like immunoreactivity. Subsequently, whole-cell patch-clamp recordings revealed heterogeneous effects of RXFP3 activation in the IGL by the RXFP3 agonist, relaxin-3 B-chain/insulin-like peptide-5 A-chain (R3/I5). Identified, neuropeptide Y-positive IGL neurons, known to influence suprachiasmatic Nucleus activity, were excited by R3/I5, whereas neurons of unidentified neurotransmitter content were either depolarized or displayed a decrease in action potential firing and/or membrane potential hyperpolarization. Our data identify a PAG to IGL relaxin-3/RXFP3 pathway that might convey stress-related information to key elements of the circadian system and influence behavioural state rhythmicity.
Sajedeh Eftekhari - One of the best experts on this subject based on the ideXlab platform.
-
localization of cgrp receptor components and receptor binding sites in rhesus monkey brainstem a detailed study using in situ hybridization immunofluorescence and autoradiography
The Journal of Comparative Neurology, 2016Co-Authors: Sajedeh Eftekhari, Renee C Gaspar, Rhonda Roberts, Tsingbau Chen, Zhizhen Zeng, Stephanie Villarreal, Lars Edvinsson, Christopher A SalvatoreAbstract:Functional imaging studies have revealed that certain brainstem areas are activated during migraine attacks. The neuropeptide calcitonin gene-related peptide (CGRP) is associated with activation of the trigeminovascular system, transmission of nociceptive information and plays a key role in migraine pathophysiology. Therefore, to elucidate the role of CGRP it is critical to identify the regions within the brainstem that processes CGRP signaling. In situ hybridization and immunofluorescence were performed to detect mRNA expression and define cellular localization of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1), respectively. To define CGRP receptor binding sites, in vitro autoradiography was performed with [(3) H]MK-3207 (a CGRP receptor antagonist). CLR and RAMP1 mRNA and protein expression were detected in the pineal gland, medial mammillary Nucleus, median eminence, infundibular stem, periaqueductal gray, area postrema, Pontine Raphe Nucleus, gracile Nucleus and spinal trigeminal Nucleus and the spinal cord. RAMP1 mRNA expression was also detected in the posterior hypothalamic area, trochlear Nucleus, dorsal Raphe Nucleus, medial lemniscus, Pontine nuclei, vagus nerve, inferior olive, abducens Nucleus, motor trigeminal Nucleus; where protein co-expression of CLR and RAMP1 was observed via immunofluorescence. [(3) H]MK-3207 showed high binding densities concordant with mRNA and protein expression. The present study suggests that several regions in the brainstem may be involved in CGRP signaling. Interestingly, we found receptor expression and antagonist binding in some areas that are not protected by the blood-brain barrier, which suggests that CGRP receptor antagonists may not need to be CNS-penetrant to antagonize receptors in these brain regions. This article is protected by copyright. All rights reserved. (Less)
Yasuhiko Ibata - One of the best experts on this subject based on the ideXlab platform.
-
Neurons expressing relaxin 3/INSL 7 in the Nucleus incertus respond to stress
The European journal of neuroscience, 2005Co-Authors: Masaki Tanaka, Yasumasa Miyamoto, Norio Iijima, Shoji Fukusumi, Yasuaki Itoh, Hitoshi Ozawa, Yasuhiko IbataAbstract:Relaxin 3/INSL 7 has recently been identified as a new member of the insulin/relaxin superfamily. Although it was reported to be dominantly expressed in the brain, its detailed distribution and function in the central nervous system are still obscure. In the present study we demonstrated that in the rat relaxin 3 was mainly expressed in neurons of the Nucleus incertus (NI) of the median dorsal tegmental pons. Other relaxin 3-expressing neurons were scattered in the Pontine Raphe Nucleus, the periaqueductal gray and dorsal area to the substantia nigra in the midbrain reticular formation. Relaxin 3-immunoreactive fibers projected particularly densely in the septum, hippocampus, lateral hypothalamus and intergeniculate leaflet of the thalamus. Ultrastructural examination revealed that relaxin 3 was localized in the dense-cored vesicles in the perikarya and was also observed in the synaptic terminals of axons. As almost all relaxin 3-containing neurons express corticotropin-releasing factor (CRF) type 1 receptor in the NI, we examined the response of relaxin 3 neurons to intracerebroventricular administration of CRF; 65% of relaxin 3 neurons expressed c-Fos 2 h after intracerebroventricular administration of 1 microg CRF. We then confirmed that c-Fos was induced in 60% of relaxin 3 neurons in the NI and the expression of relaxin 3 mRNA increased significantly in the NI after water-restraint stress. Collectively, these results suggest that relaxin 3 produced in the NI is released from nerve endings and is involved in the regulation of the stress response.
Renee C Gaspar - One of the best experts on this subject based on the ideXlab platform.
-
localization of cgrp receptor components and receptor binding sites in rhesus monkey brainstem a detailed study using in situ hybridization immunofluorescence and autoradiography
The Journal of Comparative Neurology, 2016Co-Authors: Sajedeh Eftekhari, Renee C Gaspar, Rhonda Roberts, Tsingbau Chen, Zhizhen Zeng, Stephanie Villarreal, Lars Edvinsson, Christopher A SalvatoreAbstract:Functional imaging studies have revealed that certain brainstem areas are activated during migraine attacks. The neuropeptide calcitonin gene-related peptide (CGRP) is associated with activation of the trigeminovascular system, transmission of nociceptive information and plays a key role in migraine pathophysiology. Therefore, to elucidate the role of CGRP it is critical to identify the regions within the brainstem that processes CGRP signaling. In situ hybridization and immunofluorescence were performed to detect mRNA expression and define cellular localization of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1), respectively. To define CGRP receptor binding sites, in vitro autoradiography was performed with [(3) H]MK-3207 (a CGRP receptor antagonist). CLR and RAMP1 mRNA and protein expression were detected in the pineal gland, medial mammillary Nucleus, median eminence, infundibular stem, periaqueductal gray, area postrema, Pontine Raphe Nucleus, gracile Nucleus and spinal trigeminal Nucleus and the spinal cord. RAMP1 mRNA expression was also detected in the posterior hypothalamic area, trochlear Nucleus, dorsal Raphe Nucleus, medial lemniscus, Pontine nuclei, vagus nerve, inferior olive, abducens Nucleus, motor trigeminal Nucleus; where protein co-expression of CLR and RAMP1 was observed via immunofluorescence. [(3) H]MK-3207 showed high binding densities concordant with mRNA and protein expression. The present study suggests that several regions in the brainstem may be involved in CGRP signaling. Interestingly, we found receptor expression and antagonist binding in some areas that are not protected by the blood-brain barrier, which suggests that CGRP receptor antagonists may not need to be CNS-penetrant to antagonize receptors in these brain regions. This article is protected by copyright. All rights reserved. (Less)