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Targeting nociceptive and cholinergic nerves in irradiated oropharyngeal cancer model reveals novel mechanism for dysphagia
Myers B, Islam S, Gleber Netto FO, Debnath KC, Srivastava S, Xie T, Akhter S, Adebayo AA, Miller J, Lothumalia S, Sathiskumar HN, Amit M (2024) Targeting nociceptive and cholinergic nerves in irradiated oropharyngeal cancer model reveals novel mechanism for dysphagia. Cancer Neuroscience Symposium
Objective: Explore the hypothesis that modulation of cholinergic (CHAT+) and nociceptive (CGRP+) neurons correlate with improved dysphagia.
Summary: Oropharyngeal squamous cell carcinoma is one of the most common types of head and neck cancer. Treatment for OPSCC includes surgery, radiation therapy, chemotherapy, or a combination of therapies. Despite advances in treatment, dysphagia (difficulty swallowing) is still a major burden for patients with OPSCC. The study established a novel murine OPSCC model to explore the role of nerves in dysphagia with cholinergic (CHAT) and nociceptive (CGRP) neurons playing an important role in swallowing outcomes. Targeting CHAT and CGRP could be a novel strategy for OPSCC patients with dysphagia.
Usage: 500 ng of Anti-ChAT-SAP was injected into the trigeminal ganglion in mice.
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An acetylcholine-dopamine interaction in the nucleus accumbens and its involvement in ethanol’s dopamine-releasing effect.
Loftén A, Adermark L, Ericson M, Söderpalm B (2021) An acetylcholine-dopamine interaction in the nucleus accumbens and its involvement in ethanol’s dopamine-releasing effect. Addict Biol 26(3):e12959. doi: 10.1111/adb.12959
Summary: Basal extracellular levels of dopamine within the nucleus accumbens are not sustained by muscarinic acetylcholine, whereas accumbal Cholinergic interneurons-ACh are involved in mediating ethanol-induced dopamine release.
Usage: Anti-ChAT-SAP or Rabbit IgG-SAP were infused at a flow rate of 0.05 μl/min for 10 min giving a total volume of 0.5 μl.
Related Products: Anti-ChAT-SAP (Cat. #IT-42), Rabbit IgG-SAP (Cat. #IT-35)
Striatal cholinergic interneurons exert inhibition on competing default behaviours controlled by the nucleus accumbens and dorsolateral striatum.
Ashkenazi SL, Polis B, David O, Morris G (2021) Striatal cholinergic interneurons exert inhibition on competing default behaviours controlled by the nucleus accumbens and dorsolateral striatum. Eur J Neurosci 53(7):2078-2089. doi: 10.1111/ejn.14873
Objective: To determine whether cholinergic interneurons contribute to the competition between both ventral and dorsolateral control systems.
Summary: Findings indicate a central role of cholinergic interneurons in regulating motivational impact on striatally controlled behaviors.
Usage: Anti-ChAT-SAP was diluted to 0.5 μg/μl in phosphate buffer saline and 0.5 μl were injected in each injection site.
Related Products: Anti-ChAT-SAP (Cat. #IT-42)
An acetylcholine-dopamine interaction in the rat nucleus accumbens and its tentative involvement in ethanol’s dopamine-liberating effect
Andrén A, Adermark L, Söderpalm B, Ericson M (2019) An acetylcholine-dopamine interaction in the rat nucleus accumbens and its tentative involvement in ethanol’s dopamine-liberating effect. Neuroscience 2019 Abstracts 079.08. Society for Neuroscience, Chicago, IL.
Summary: Alcohol use disorder is a chronic, relapsing brain disorder associated with serious medical consequences leading to preterm death. Although few in number, cholinergic interneurons (CIN) have arisen as an important cell population within the nucleus accumbens (nAc) that may exert a regulatory impact on dopamine (DA) neurotransmission locally. A defect in CIN have been suggested to be involved in psychiatric diseases such as alcohol addiction. The mechanisms through which endogenous cholinergic activity modulates DA release in response to ethanol administration and its role in development of addiction is not known. In this project, the aim was to study if acetylcholine (ACh) can influence DA release locally in the nAc and if so, through which receptor population(s) this effect is mediated. Further, we wanted to determine the role of ACh in ethanol-induced DA elevation.Using reversed in vivo microdialysis, the acetylcholinesterase inhibitor physostigmine was administered locally in the nAc of male Wistar rats followed by addition of either the muscarinic ACh receptor inhibitor scopolamine or the nicotinergic ACh receptor inhibitor mecamylamine. Subsequently, ethanol was perfused following local pretreatment with scopolamine or mecamylamine, using the same methodology. An immunotoxin, anti-ChAT-saporine, was infused locally into the nAc of a subset of male Wistar rats to selectively lesion CIN, followed by local ethanol administration via reversed in vivo microdialysis. Local administration of physostigmine induced a DA elevation within the nAc, an effect blocked by scopolamine but not by mecamylamine. Local administration of ethanol increased DA levels. Scopolamine pretreatment non-significantly attenuated the ethanol-induced DA elevation, whereas pretreatment with mecamylamine had no effect. Preliminary results indicate a minor attenuation of the DA elevation observed after local administration of ethanol in toxin-treated animals, as compared to sham-treated controls. Taken together, these results suggest that ACh increases extracellular DA levels in nAc in vivo, an effect mediated by muscarinic ACh-receptors and not by nicotinic ACh-receptors. Considering that scopolamine moderately attenuated ethanol-induced DA output and that lesioning of CIN appeared to hamper DA release in response to ethanol, ACh release from CIN within the nAc may be partially involved in ethanol-induced DA release in nAc.
Related Products: Anti-ChAT-SAP (Cat. #IT-42)
Cholinergic neural activity directs retinal layer-specific angiogenesis and blood retinal barrier formation.
Weiner GA, Shah SH, Angelopoulos CM, Bartakova AB, Pulido RS, Murphy A, Nudleman E, Daneman R, Goldberg JL (2019) Cholinergic neural activity directs retinal layer-specific angiogenesis and blood retinal barrier formation. Nat Commun 10(1):2477. doi: 10.1038/s41467-019-10219-8
Objective: To determine which neurons are responsible for angiogenesis and blood retinal barrier formation.
Summary: Anti-ChAT-SAP reduces SAC (starburst amacrine cell) number and inhibits deep-layer angiogenesis.
Usage: Anti-ChAT-SAP or control Rabbit-IgG-SAP were injected intravitreally at P3 and P11 (0.12 mg/mL in PBS).
Related Products: Anti-ChAT-SAP (Cat. #IT-42), Rabbit IgG-SAP (Cat. #IT-35)
Featured Article: Impaired reach-to-grasp responses in mice depleted of striatal cholinergic interneurons
Abudukeyoumu N, Garcia-Munoz M, Nakano Y, Arbuthnott GW (2018) Featured Article: Impaired reach-to-grasp responses in mice depleted of striatal cholinergic interneurons. Targeting Trends 19
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Read the featured article in Targeting Trends.
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Impaired reach-to-grasp responses in mice depleted of striatal cholinergic interneurons
Abudukeyoumu N, Garcia-Munoz M, Nakano Y, Arbuthnott GW (2018) Impaired reach-to-grasp responses in mice depleted of striatal cholinergic interneurons. Neuroscience 2018 Abstracts 491.01 / MM13. Society for Neuroscience, San Diego, CA.
Summary: Cholinergic interneurons (ChIs) are sparsely distributed within the striatum, a nucleus that plays important role in voluntary motor control, associated learning, procedural memory, action selection and planning and execution of movement. Sparsely distributed ChIs are 1-3% of all striatal neurons and the main source of striatal acetylcholine. Here we report the effect of depletion of ChIs in the dorsolateral striatum in a reach-to-grasp task. To selectively deplete ChIs, we used the saporin ribosome-inactivating-immunotoxin that targets choline acetyltransferase. C57BL/J male mice, 21 days old, received a stereotaxic unilateral infusion of the toxin (0.3µl/3min), and sham control group was injected with saline. Following one week postsurgery recovery, animals were food deprived for 12 h everyday and trained for 12 days at night during their active circadian cycle. The mean percentage ± SEM of successful performance in the reach-to-grasp task for the last 6 training sessions was 51.11 ± 4.09% (n = 25), 48.79 ± 7.7% (n = 9) and 26.28 ± 5.19% (n = 13) for intact control, sham control and ChIs-depleted mice, respectively. These results indicate that striatal depletion of ChIs impair reaching accuracy, whereas no significant differences were observed in control or sham operated mice. Moreover, a positive correlation between loss of ChIs and performance in the reach-to-grasp task was observed. Our results suggest that the participation of ChIs in striatal mediated motor learning impact on the function of interneurons and projection neurons of the whole striatal microcircuitry (Abudukeyoumu, N., Hernandez-Flores, T. et al. Eur. J. Neuroscience, in press).
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ATS Poster of the Year Winner. Read the featured article in Targeting Trends.
A streamlined method for the preparation of gelatin embedded brains and simplified organization of sections for serial reconstructions
Liu A, Aoki S, Wickens J (2017) A streamlined method for the preparation of gelatin embedded brains and simplified organization of sections for serial reconstructions. Bio-protocol 7(22):e2610.. doi: 10.21769/BioProtoc.2610
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Selective cholinergic depletion of pedunculopontine tegmental nucleus aggravates freezing of gait in parkinsonian rats
Xiao H, Li M, Cai J, Li N, Zhou M, Wen P, Xie Z, Wang Q, Chang J, Zhang W (2017) Selective cholinergic depletion of pedunculopontine tegmental nucleus aggravates freezing of gait in parkinsonian rats. Neurosci Lett 659:92-98.. doi: 10.1016/j.neulet.2017.08.016
Summary: Many patients with advanced Parkinson’s disease suffer from gait and postural impairments. The authors used Anti-ChAT-SAP (Cat. #IT-42) to specifically lesion neurons in the Pedunculopontine Tegmental Nucleus (PPTg) to examine the impact on gait performance. Adult male rats received either unilateral PPTg cholinergic lesion or bilateral PPTg lesion, at a dose of 250 ng. The authors conclude that the cholinergic neurons of pedunculopontine tegmental nucleus play a vital role in the occurrence of gait freezing in Parkinson’s disease.
Related Products: Anti-ChAT-SAP (Cat. #IT-42)
Striatal cholinergic interneurons: their depletion and its progression.
Abudukeyoumu N, Garcia-Munoz M, Jaidar OP, Arbuthnott G (2016) Striatal cholinergic interneurons: their depletion and its progression. Neuroscience 2016 Abstracts 245.09 / RR4. Society for Neuroscience, San Diego, CA.
Summary: Even before the discovery that Parkinson’s was produced by the loss of dopaminergic neurons, this neurological disease was treated with anticholinergic drugs. A balance between cholinergic and dopaminergic activity in striatum is not only important in PD but for the normal function of the nucleus (i.e., behavior, reward, memory and cognitive functions). An important source of striatal acetylcholine (Ach) comes from giant and sparsely distributed cholinergic interneurons (ChI). However, their study has been hampered by a concentration of only 1-3 % of the whole striatal cell population. We performed a stereological systematic random sampling of striatal tissue from 21 days old C57BL/6J male mice. To selectively deplete ChI we performed a stereotaxic injection of saporin ribosome inactivating immunotoxin that targets choline acetyltransferase (0.3µl). Following survival periods of 2, 4 or 6 weeks, animals were sacrificed and brain sections immunostained against ChAT to identify ChI, or against vesicular acetylcholine transporter (vAChT) to identify synaptic boutons. For each of the three survival periods, we counted and compared the number of ChIs between the intact and the lesioned hemispheres and the change in the number of vesicular acetylcholine transporters (vAChT). Compared to striatal sections from naïve controls and sham injections, we observed a decrease in ChIs according to each survival period of 24.4% (week 2, n=9), 33.74% (week 4, n= 11) and 19.89% (week 6, n=10). In contrast, we observed a percent increase in vAChT positive boutons of 42.3, 21.6 and 28.3% for each of the respective survival periods (n=9, n=11 and n=10). We are investigating whether the increase in vAChT positive terminals is due to an indirect upregulation produced by compensatory axonal sprouting from surviving ChI, or from afferent axonal terminal fields of cholinergic mesopontine neurons.
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