Gut Brain Axis

Helicobacter pylori Induced Anxiety and Anorexia
Our PGP9.5 was used as a Hypothalamic Neuronal Marker in this study-Hajime Suzuki, Koji Ataka, Akihiro Asakawa, Kai-Chun Cheng, Miharu Ushikai, Haruki Iwai, Takakazu Yagi, Takeshi Arai, Kinnosuke Yahiro, Katsuhiro Yamamoto, Yoshito Yokoyama, Masayasu Kojima, Toshihiko Yada, Toshiya Hirayama, Norifumi Nakamura & Akio Inui (2019). Helicobacter pylori Vacuolating Cytotoxin A Causes Anorexia and Anxiety via Hypothalamic Urocortin 1 in Mice. Scientific Reports volume 9, Article number: 6011.

Images: Ucn1- and DAPI-positive cells (yellow arrow heads), or Ucn1- and PGP9.5-positive cells (white arrow heads) in the PVN cells.

This is the first study demonstrating the anorexigenic and anxiogenic effects of VacA. The authors propose the following. VacA secreted by Hp in the stomach travels via the peripheral circulation and passes through the BBB. VacA binds to LRP1 and activates the intracellular PLC-PKC pathway, resulting in the activation of Ucn1-positive neurons, such as in the PVN of the hypothalamus. Secreted Ucn1 induces the inhibition of food intake through CRF2 receptors and anxiety through CRF1 receptors (Fig. 6). The central Ucn1-CRF receptor axis activated by VacA might be a new important pathway that contributes to the anorexigenic and anxiogenic effects of Hp infection and could be a therapeutic target for Hp-induced alterations.

Neuronal Markers

New Pub References 3 Markers
We are recognized for our large catalog of neuronal markers. Our strength, in this area, includes markers designed for pain researchers.

They are widely used and frequently published. This new publication references use of our Guinea Pig Substance P, Guinea Pig PGP9.5 and Chicken NF200 of NF-Heavy. andla, Jagadeesha, Lomada, Santosh Kumara, Jianninga; Kuner, Rohinia, Bali, Kiran Kumar. miR-34c-5p functions as pronociceptive microRNA in cancer pain by targeting Cav2.3 containing calcium channels. Pain: September 2017 - Volume 158 - Issue 9 - p 1765–1779 doi: 10.1097/j.pain.0000000000000971.

Neuromics' PGP9.5 Staining of  Mouse DRGs.

.Neuromics SP and NF200 Staining of Mouse DRGSs

Schwann Cell-Sensory Neurons-PNS Markers

Data-Publications
These markers a important tools for the study of Neuro-muscular diseases like Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS).

For Neuromuscular Disease Researchers, we have some of the best Schwann Cell and Sensory/Peripheral Neuron Markers in the business.

Images: Rat mixed neuron/glial cultures stained with Peripherin (green channel) and Neurofilament alpha-internexin/NF66 (green channel). These cultures contain mostly neurons which are rich in alpha-internexin, and a subgroup which have a large amount of peripherin also, such as the prominent cell in the middle of the micrograph. Since this cell expresses large amounts of peripherin and alpha-internexin, the green and red signals superimpose to produce a golden cell. Blue is a DNA stain. Protocol on data-sheet.

Here're recent publications referencing use of these markers:
Leah R. Reznikov, Qian Dong, Jeng-Haur Chena, Thomas O. Moninger, Jung Min Park, Yuzhou Zhang, Jianyang Du, Michael S. Hildebrand, Richard J. H. Smith, Christoph O. Randak, David A. Stoltz, and Michael J. Welsh. CFTR-deficient pigs display peripheral nervous system defects at birth. www.pnas.org/cgi/doi/10.1073/pnas.1222729110...goat anti-p75 (1:500; Neuromics)...

Gayle M. Passmore, Joanne M. Reilly, Matthew Thakur, Vanessa N. Keasberry, Stephen J. Marsh, Anthony H. Dickenson and David A. Brown. Functional significance of M-type potassium channels in nociceptive cutaneous sensory endings. Fronteirs in Molecular Science. doi: 10.3389/fnmol.2012.00063. ...neurofilament H (1:1000,Neuromics,USA)...

Leigh A Nattkemper, Zhong-Qiu Zhao, Anna J Nichols, Alexandru D P Papoiu, Carol A Shively, Zhou-Feng Chen and Gil Yosipovitch. Over-Expression of the Gastrin-Releasing Peptide in Cutaneous Nerve Fibers and its Receptor in Spinal Cord in Primates with Chronic Itch. Journal of Investigative Dermatology accepted article preview 4 April 2013; doi: 10.1038/jid.2013.166...Protein Gene Product 9.5 (PGP9.5; Neuromics, Edina, MN).

Wiebke Kallenborn-Gerhardt, Katrin Schröder, Domenico Del Turco, Ruirui Lu, Katharina Kynast, Judith Kosowski, Ellen Niederberger, Ajay M. Shah, Ralf P. Brandes, Gerd Geisslinger, and Achim Schmidtko. NADPH Oxidase-4 Maintains Neuropathic Pain after Peripheral Nerve Injury. The Journal of Neuroscience, 25 July 2012, 32(30): 10136-10145; doi: 10.1523/​JNEUROSCI.6227-11.2012...chicken anti-P-Zero or MPZ (1:500; Neuromics)...

Images: Micrographs depicting SSeCKS colocalization with myelination markers (CNPase and Pzero). (A) SSeCKS (red) and CNPase (green) in the lumbar spinal cord dorsal horn. The labeling appears discrete with minimal colocalization. (B) SSeCKS (red) and Pzero (green) in the L4 dorsal root ganglia. A lack of co-localization is observed and Pzero can be seen localized to putative axonal elements (arrow). (C) SSeCKS (red) and Pzero (green) in the sciatic nerve. As in the dorsal root ganglia, a lack of co-localization is observed. Both SSeCKS and Pzero can be seen localized to axonal elements. (D) SSeCKS (red) and Pzero (green) in glabrous skin of the hind-paw, fibers displaying colocalization (yellow) can be observed (arrow). Irmen et al. Journal of Brachial Plexus and Peripheral Nerve Injury 2008 3:8 doi:10.1186/1749-7221-3-8.

I will post new data and pubs as they become available.

More on the Neurobiology of Itch

I have an earlier posting on neuro-transmission of itch or pruritis. This focused on the role of Toll-like Receptor 3 (TLR 3). This posting looks at the role of Gastrin-Releasing Protein (GRP) and the Gastrin-Releasing Protein Receptor (CRPR) in chronic itch. The findings are important because this condition affects millions worldwide and results in a costly erosion of quality of life.

Here chronic itch was studied in Macque Monkeys over a period of 4 years. The expression patterns of GRP, GRPR and PGP9.5 were accessed by immunohistochemistry: Leigh A Nattkemper, Zhong-Qiu Zhao, Anna J Nichols, Alexandru D P Papoiu, Carol A Shively, Zhou-Feng Chen and Gil Yosipovitch. Over-Expression of the Gastrin-Releasing Peptide in Cutaneous Nerve Fibers and its Receptor in Spinal Cord in Primates with Chronic Itch. Journal of Investigative Dermatology accepted article preview 4 April 2013; doi: 10.1038/jid.2013.166.

Images: Double labeling of PGP9.5 and GRP in skin of primates representing mild, moderate and severe itch. Primates with higher scratching severity showed in increase in the co-localization of PGP9.5 and CRP at the dermal-epidermal junctions (arrows).

In addition to increased PGP9.5/GRP expression in the skin, similar results were shown for expression of GRP/GRPR in DRGs. This makes GRP and its receptor candidate drug targets for chronic itch or pruritis in humans.

Epidermal Nerve Fibers in Neuropathic Pain Model

Re-innervation in spared nerve injury (SNI) vs normal rats
Neuromics' Pain and Inflammation Research Antibodies are frequently used to help researchers find root causes of neuropathic pain. This is a fascinating study of re-innervation patterns of epidermal and dermal nerve fibers in a rat neuropathic pain model (Note: our Guinea Pig Polyclonal P2X3 Antibody was used in this study): Liron S. Durakua, Mehdi Hossaini, Barthold N. Schüttenhelm, b, Joan C. Holstege, Martijn Baas, Tom J.H. Ruigrok, Erik T. Walbeehm. Re-innervation patterns by peptidergic Substance-P, non-peptidergic P2X3, and myelinated NF-200 nerve fibers in epidermis and dermis of rats with neuropathic pain. Experimental Neurology Volume 241, March 2013, Pages 13–24. doi.org/10.1016/j.expneurol.2012.11.029.

Non-footpad area vs. footpad.The distribution pattern between the center non-footpad area and footpad is compared for the different subgroups of sensory skin fibers. For epidermal Sub P-IR and upper dermal NF-200-IR fibers there is an equal density of fibers in the center and footpad area suggesting a homogenous distribution over the foot sole of a rat. Whereas for epidermal P2X3-IR fibers there is a significant lower number of P2X3-IR fibers in the footpads as compared to the center non-footpad area, suggesting a heterogeneous distribution in the foot sole for this type of sensory fibers. N = 5 per group. Unpaired t-test. ***: p < 0,001. Scale bar: 250 μm. doi.org/10.1016/j.expneurol.2012.11.029

Illustration of the skin innervation in normal and SNI situation.Illustration showing the innervation pattern of subgroups of sensory skin fibers in the normal situation and in the SNI model 10 weeks PO. In the naïve animals the peptidergic CGRP and non-peptidergic P2X3 fibers have a lower density in the footpads as compared to the non-footpad areas, while the Substance P and NF-200 fibers have an equal distribution over the complete foot sole. In the SNI model there is a significant increase of CGRP epidermal fibers in the medial and lateral area of the foot sole and there is a complete re-innervation of the center area. In addition the footpads in the SNI model are hyper-innervated with CGRP fibers. Substance P and P2X3 and NF-200 fibers show no increased density in the uninjured medial and lateral area after 10 weeks PO. In addition, Substance P and P2X3 fibers hardly re-innervate the center area; however, the NF-200 fibers have the same density of fibers in the denervated area as in the normal situation. In the SNI model the medial, center and lateral area have all an increase in LC's, with the center area being the most prominent one. In addition the epidermis thickness of the SNI model has decreased significantly in all the three areas after 10 weeks PO.
Related Postings: http://neuromics.blogspot.com/search/label/Neuropathic%20Pain.