i-Fect Delivers Again and Again

Silencing Lactate Dehydrogenase A in vivo

Pathologic CNS is characterized by neuronal damage that leads to the release of intracellular components. However, the effect of damaged cells on angiogenesis has not been clarified. This study revealed that LDHA, which is a known damage marker, promotes CNS-specific angiogenesis. LDHA-mediated angiogenesis depends on vimentin on the surface of vascular endothelial cells. The work described here proposes a novel mechanism by which neurodegeneration drives angiogenesis in the CNS.

A mixture of our i-Fect^TM and LDHA siRNA, in this study, were directly injected into mice cortexes: Hsiaoyun Lin, Rieko Muramatsu, Noriko Maedera, Hiroto Tsunematsu, Machika Hamaguchi, Yoshihisa Koyama, Mariko Kuroda, Kenji Ono, Makoto Sawada, Toshihide Yamashita. Extracellular Lactate Dehydrogenase A Release From Damaged Neurons Drives Central Nervous System Angiogenesis. doi.org/10.1016/j.ebiom.2017.10.033.

Images: LDHA is sufficient to evoke CNS angiogenesis. (a) Representative images of CD105-labeled spinal cord sections obtained 7 days after LDHA administration. (b) Length of CD105+ neovessels around the LDHA administration site as indicated in a, n = 5 each. (c) Representative image of a Nissl-stained brain section after controlled cortical impact (CCI). (d) Representative image of the CD105-immunolabelled cerebral cortex obtained 7 days after CCI. (e) Length of CD105+ neovessels around CCI lesions as indicated in d; n = 5 each, all error bars represent the s.e.m. **P < 0.01, Student's t-tests. Scale bars, 200 μm.

The findings reveal unexpected neurovascular interactions in the injured adult CNS that may be relevant to our understanding of neuronal damage, which is a hallmark of many CNS disorders

Human Growth Factor+Neurotrophin+Cytokine Array-Test 40 Markers in on Assay

Sensitive, Specific and Cost Effective

Neuro-immuno and degenerative diseases and disorders commonly show dysregulation of Growth Factors and Cytokines. Using our Quantibody Neuroscience Arrays, we have measured the blood serum of clients with Neuro-inflammatory/immune response diseases/disorders including Autism Spectrum Disorder (ASD). Most showed lowered levels of Growth Factors/Neurotrophins and elevated levels of Inflammatory Response Cytokines.

In order to expand the number of biomarkers measured, we are pleased to announce the addition of our New Growth Factor+Neurotrophin+Cytokine Array. This will enable us to further determine the "finger prints" of these diseases/disorders at the protein level. This array includes: Immunogen: Amphiregulin, BDNF, bFGF, BMP-4, BMP-5, BMP-7, beta-NGF, EGF, EGFR, EG-VEGF (PK1), FGF-4,FGF-7 (KGF), GDF-15, GDNF, Growth Hormone, HB-EGF, HGF, IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-4, IGFBP-6, IGF-1, Insulin, M-CSF R, NGFR (TNFRSF16), NT-3, NT-4, Osteoprotegerin (TNFRSF11B), PDGF-AA, PLGF, SCF, SCF R (CD117/c-kit), TGF alpha, TGF beta 1, TGF beta 3, VEGF-A, VEGFR2, VEGFR3 and VEGF-D.

I will continue to post testing results here.

Solutions for Studying Neuro-degeneration

Data Rich and Frequently Published

The Neuromics' brand is built, in part, by our proven ability to provide solutions for the study of neuro-degeneration. These include:

• Neuronal-Glial Markers
• Primary Neurons and Astrocytes
• Apoptosis Research Reagents
• Transfection Reagents

A recent example shows the use of one of  MAP-2 markers to study hearing decline with age: Radtke-schuller S, Seeler S and Grothe B(2015) Restricted loss of olivocochlear but not vestibular efferent neurons in the senescent gerbil (Meriones unguiculatus). Front. Aging Neurosci. 7:4. doi:10.3389/fnagi.2015.00004.

Figure: Lipofuscin granules in MSO neurons of an aged gerbil. MSO neurons are MAP2 immunostained (Alexa Fluor 647, red). Lipofuscin granules have been excited with the DAPI excitation wavelengths and appear blue. Confocal images show a maximum projection of image stacks in A and a single optical image of 0.3 µm thickness in the enlargement in B. Scale bar in A: 50 µm and 20 µm in B.

We stand ready to serve you. Should you have interest or questions, do not hesitate to contact me directly: Pete Shuster-Owner/CEO-pshuster@neuromics.com or direct phone: 612-801-1007. Thank you.

Good Axon; Bad Axon: Regeneration in the CNS and Age

"The incapacity of the central nervous pathways to regenerate is a dogma accepted by science..." - Ramon y Cajal


Harvard University has opened access to Michio Wendell Painter's Dissertation: Regeneration in the aging peripheral nervous system. Will Spinal Cord Injury (SCI) and Neurodegenerative Diseases of the PNS become treatable with regenerative therapies? This work provides important insights.

Age plays a central role in regenerative capacities.

Quantibody® Cytokine Arrays

Cytokines, Adipokines, Growth Factors and Neurotrophins

We are pleased to announce addition of Antibody Arrays to our catalog. These are excellent tools for study apoptosis, inflammation, angiogenesis and  immune response and related autoimmune, inflammatory and degenerative diseases plus many forms of cancers. Check out this video.

Specific Research Applications Include:
•High-throughput profiling of cytokine expression
•Validation of semi-quantitative antibody array results
•Identifying potential molecular targets for drug development
•Identifying the molecular mechanisms of drug action
•Identifying crucial factors involved in disease processes
•Discovering biomarkers for disease management
•Discovering expression patterns for molecular classification of diseases

How Quantibody Arrays Work

We will be aggresively adding new arrays to our product offerings in June. Stay tuned for more.





PINK1 and Alzheimer's and Multiple Sclerosis

I would like to highlight a recent publication referencing use of our PTEN-induced kinase/PINK1 Antibody.

Jack Van Horssen et al. investigated PINK1 expression in well-characterized brain samples derived from MS and AD individuals using immunohistochemistry.

Micha M.M. Wilhelmus, Susanne M.A. van der Pol, Quentin Jansen, Maarten E. Witte, Paul van der Valk, Annemieke J.M. Rozemuller, Benjamin Drukarch, Helga E. de Vries and Jack Van Horssen. Association of Parkinson disease-related protein PINK1 with Alzheimer disease and multiple sclerosis brain lesions. Free Radical Biology and Medicine. Volume 50, Issue 3, 1 February 2011, Pages 469-476.

Abstract: Mitochondrial dysfunction and oxidative stress are hallmarks of various neurological disorders, including multiple sclerosis (MS), Alzheimer disease (AD), and Parkinson disease (PD). Mutations in PINK1, a mitochondrial kinase, have been linked to the occurrence of early onset parkinsonism. Currently, various studies support the notion of a neuroprotective role for PINK1, as it protects cells from stress-mediated mitochondrial dysfunction, oxidative stress, and apoptosis. Because information about the distribution pattern of PINK1 in neurological diseases other than PD is scarce, we here investigated PINK1 expression in well-characterized brain samples derived from MS and AD individuals using immunohistochemistry. In control gray matter PINK1 immunoreactivity was observed in neurons, particularly neurons in layers IV–VI. Astrocytes were the most prominent cell type decorated by anti-PINK1 antibody in the white matter. In addition, PINK1 staining was observed in the cerebrovasculature. In AD, PINK1 was found to colocalize with classic senile plaques and vascular amyloid depositions, as well as reactive astrocytes associated with the characteristic AD lesions. Interestingly, PINK1 was absent from neurofibrillary tangles. In active demyelinating MS lesions we observed a marked astrocytic PINK1 immunostaining, whereas astrocytes in chronic lesions were weakly stained. Taken together, we observed PINK1 immunostaining in both AD and MS lesions, predominantly in reactive astrocytes associated with these lesions, suggesting that the increase in astrocytic PINK1 protein might be an intrinsic protective mechanism to limit cellular injury.

Immunohistochemistry

Immunohistochemistry was used to detect PINK1 immunostaining in temporal neocortex and white matter in AD, MS, and control subjects. Cryosections (5 μm) were air-dried and fixed in acetone for 10 min. Next, sections were incubated with an affinity-purified rabbit anti-PINK1 antibody (1:100; Neuromics, Edina, MN, USA) for 60 min at room temperature. Then, the slides were incubated with EnVision kit horseradish peroxidase-labeled anti-mouse/rabbit (DAKO, Glostrup, Denmark) for 30 min at room temperature and finally diaminobenzidine tetrachloride. Between incubation steps, sections were thoroughly washed with phosphate-buffered saline (PBS). After a short rinse in tap water sections were incubated with hematoxylin for 1 min and extensively washed with tap water for 10 min. Finally, sections were dehydrated with ethanol followed by xylol and mounted with Entellan (Merck, Darmstadt, Germany). All antibodies were diluted in PBS containing 0.1% bovine serum albumin (Boehringer–Mannheim, Germany), which also served as a negative control. Negative controls were essentially blank.

Image: In active lesions PINK1 immunostaining was intense in reactive astrocytes (arrows). Double labeling of PINK1 (green) with the astrocytic marker GFAP (red) demonstrated PINK1 expression in astrocytes (inset).

Related Reagents:

Neurodegenerative Disease Research
Antibodies

Neurodegenerative Disease Research Proteins

Neurotransmission
-Neurotransmission Research Antibody Categories

Neurotrophins and Growth Factor Antibodies

Neuron-Glial Expressed-Includes
Neurotrophin Proteins

Primary Neurons and Astrocytes
-Primary human, rat and mouse neurons and astrocytes by Category