References

Lecrux C, Sandoe C, Neupane S, Kropf P, Toussay X, Tong X, Lacalle-Aurioles M, Shmuel A, Hamel E (2017) Impact of altered cholinergic tones on the neurovascular coupling response to whisker stimulation. J Neurosci 37:1518-1531. doi: 10.1523/JNEUROSCI.1784-16.2016

Summary: The authors assessed the effects of varying ACh tone on whisker-evoked NVC responses in rat barrel cortex. ACh depletion was achieved via unilateral icv injection (4 mcg/2 mcl) with 192 IgG-SAP (Cat. #IT-01) or saline. They conclude that ACh is not only a facilitator, but also a prerequisite for the full expression of sensory-evoked NVC responses.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Wang D, Wang A, Wu F, Qiu X, Li Y, Chu J, Huang WC, Xu K, Gong X, Li S (2017) Sox10+ adult stem cells contribute to biomaterial encapsulation and microvascularization. Sci Rep 7:40295. doi: 10.1038/srep40295 PMID: 28071739

Objective: To show that Sox10+ adult stem cells contribute to both encapsulation and microvessel formation.

Summary: This study provides a novel mechanism that Sox10+ adult stem cells in the stroma of subcutaneous loose connective tissues are a common precursor of fibroblasts/myofibroblasts and perivascular cells. These adult stem cells can first differentiate into fibroblast-like cells at early stages of biomaterials implantation, and then into myofibroblasts promoting encapsulation/fibrosis, or perivascular cells supporting microvessels.

Usage: flow cytometry

Related Products: NGFR (mu p75) Rabbit Polyclonal, affinity-purified (Cat. #AB-N01AP)

Kelly SC, Nelson PT, Counts SE (2017) Featured Article: The locus coeruleus: a potential link between cerebrovascular and neuronal pathology in Alzheimer’s disease. Targeting Trends 18

Related Products: Anti-DBH-SAP (Cat. #IT-03), Mouse IgG-SAP (Cat. #IT-18)

Read the featured article in Targeting Trends.

See Also:

• Kelly SC et al. The locus coeruleus: a potential link between cerebrovascular and neuronal pathology in Alzheimer’s disease. Neuroscience 2016 Abstracts 786.11 / H7, 2016. Society for Neuroscience, San Diego, CA

Konig N, Trolle C, Kapuralin K, Adameyko I, Mitrecic D, Aldskogius H, Shortland PJ, Kozlova EN (2017) Murine neural crest stem cells and embryonic stem cell-derived neuron precursors survive and differentiate after transplantation in a model of dorsal root avulsion. J Tissue Eng Regen Med 11(1):129-137. doi: 10.1002/term.1893 PMID: 24753366

Objective: To compare survival and migration of murine boundary cap neural crest stem cells (bNCSCs) and embryonic stem cells (ESCs)-derived, pre-differentiated neuron precursors after their implantation acutely at the junction between avulsed dorsal roots L3-L6 and the spinal cord.

Summary: The data show that both stem cell types successfully survived implantation to the acutely injured spinal cord and maintained their differentiation and migration potential. The data suggest that, depending on the source of neural stem cells, they can play different beneficial roles for recovery after dorsal root avulsion.

Usage: immunohistochemistry (1:500)

Related Products: NGFR (mu p75) Rabbit Polyclonal, affinity-purified (Cat. #AB-N01AP)

Bolaina-Lorenzo E, Martínez-Ramos C, Monleón-Pradas M, Herrera-Kao W, Cauich-Rodríguez JV, Cervantes-Uc JM (2016) Electrospun polycaprolactone/chitosan scaffolds for nerve tissue engineering: physicochemical characterization and Schwann cell biocompatibility. Biomed Mater 12(1):015008. doi: 10.1088/1748-605x/12/1/015008 PMID: 27934786

Objective: To study the effect of scaffold compositions on its physicochemical and biological properties.

Summary: Immunochemistry analysis with p75 analysis confirmed that the cells exhibited a Schwann cell phenotype, suggesting that electrospun polycaprolactone/chitosan scaffolds would be good candidates for peripheral nerve tissue engineering.

Usage: IHC (1:100)

Related Products: NGFr (mu p75) Rabbit Polyclonal, affinity-purified (Cat. #AB-N01AP)

Turnbull M, Coulson E (2017) Cholinergic basal forebrain lesion decreases neurotrophin signaling without affecting tau hyperphosphorylation in genetically susceptible mice. J Alzheimers Dis 55:1141-1154.. doi: 10.3233/JAD-160805

Summary: Alzheimer’s disease(AD) is a progressive, irreversible neurodegenerative disease that destroys memory and cognitive function. Aggregates of hyperphosphorylated tau protein are a prominent feature in the brain of patients with AD, and area major contributor to neuronal toxicity and disease progression. However, the factors that initiate the toxic cascade that results in tau hyperphosphorylation in AD are unknown. The authors investigated whether degeneration of basal forebrain cholinergic neurons (BFCNs) and/or resultant decrease in neurotrophin signaling cause aberrant tau hyperphosphorylation. Two-month-old male and female pR5 mice were infused with murine p75-SAP (Cat. #IT-16) at a concentration of 0.4 mg/ml or 0.4 mg/ml of control Rabbit IgG-SAP (Cat. #IT-35) using a 30G needle attached to a 5 ml Hamilton syringe and pump. The needle was lowered into the medial septum according to coordinates in a mouse brain atlas, and the toxin was infused at a rate of 0.4 ul/min (1.5 u total volume). The results reveal that the loss of BFCNs in pre-symptomatic pR5 tau transgenic mice results in a decrease in hippocampal brain-derived neurotrophic factor levels and reduced TrkB receptor activation. However, there was no exacerbation of the levels of phosphorylated tau or its aggregation in the hippocampus of susceptible mice. Furthermore the animals’ performance in a hippocampal-dependent learning and memory task was unaltered, and no changes in hippocampal synaptic markers were observed. This suggests that tau pathology is likely to be regulated independently of BFCN degeneration and the corresponding decrease in hippocampal neurotrophin levels, although these features may still contribute to disease etiology.

Related Products: mu p75-SAP (Cat. #IT-16), Rabbit IgG-SAP (Cat. #IT-35)

Maass J, Gu R, Cai T, Wan Y, Cantellano S, Asprer J, Zhang H, Jen H, Edlund R, Liu Z, Groves A (2016) Transcriptomic analysis of mouse cochlear supporting cell maturation reveals large-scale changes in notch responsiveness prior to the onset of hearing. PLoS One 11:e0167286. doi: 10.1371/journal.pone.0167286 PMID: 27918591

Summary: The ability of neonatal mouse cochlear supporting cells to divide and differentiate into hair cells is very limited and declines in the first two weeks after birth. This decline is associated with the morphological and functional maturation of the organ of Corti prior to the onset of hearing, however little is known of the molecular changes that underlie these events. The authors attempt to identify these changes using RNA-seq to generate transcriptional profiles of purified cochlear supporting cells and found significant changes in gene expression related to regulation of proliferation, differentiation of inner ear components and the maturation of the organ of Corti. The authors also examined the regenerative potential of supporting cells in production of hair cells in response to a blockade of the Notch signaling pathway at the time of birth, but a complete lack of response just a few days later. Analysis included IHC on frozen sections of paraformaldehyde-fixed temporal bones of LfngEGFP mice. Anti-NGFr (mup75) (Cat. #AB-N01AP) was used at a 1:200 dilution. The results offer first molecular insights into the failure of hair cell regeneration in the mammalian cochlea.

Related Products: NGFr (mu p75) Rabbit Polyclonal, affinity-purified (Cat. #AB-N01AP)

Ha K, Bidlingmaier S, Su Y, Lee N, Liu B (2017) Identification of novel macropinocytosing human antibodies by phage display and high-content analysis. Methods Enzymol 585:91-110. doi: 10.1016/bs.mie.2016.10.004

Objective: To describe a method for identifying antibodies that internalize via macropinocytosis by screening phage-displayed single-chain antibody selection outputs with an automated fluorescent microscopy-based high-content analysis platform.

Summary: Novel phage antibodies are identified by colocalization with macropinocytosis marker, converted into full-length human antibodies, and further characterized with regard to cell binding, pathway of internalization, and intracellular payload delivery.

Usage: Biotinylated IgG is mixed with Streptavidin-ZAP in 1:1 molar ratio to form an immunotoxin that is serially-diluted in a cytotoxicity assay.

Related Products: Streptavidin-ZAP (Cat. #IT-27)

Maness EBL, Leong CS, Burk JA (2016) Effects of N-desmethylclozapine on attentional performance following loss of basal forebrain corticopetal cholinergic inputs. Neuroscience 2016 Abstracts 833.15 / HHH34. Society for Neuroscience, San Diego, CA.

Summary: Corticopetal cholinergic neurons play a vital role in attentional processing, and dysregulation of this system contributes to central nervous system disorders whose main attributes include an inability to engage in sustained attention, such as Alzheimer’s disease. The cholinergic muscarinic-1 (M1) receptor is known to be necessary for normal attentional processing. In general, there has been a trend towards supporting drugs that provide allosteric agonism of cholinergic receptors as an approach that may yield greater benefits than drugs that act at orthosteric receptor sites. There exists contention in the literature regarding the action of N-desmethylclozapine (NDMC), a partial M1-preferring agonist, that is thought to act at an allosteric site on the M1 receptor. The goal of the present experiment is to further evaluate NDMC’s activity at these sites in a lesion model of cholinergic dysfunction using an operant task assessing attentional capacity. After training in an attention-demanding task requiring differentiation between signal trials (500, 100, and 25ms illumination of a central panel light) and non-signal trials (no light illumination), Sprague Dawley rats received intrabasalis infusions of either saline or the cholinergic neurotoxin 192 IgG-saporin, and attentional performance was later measured following intracerebroventricular infusions of NDMC. In general, NDMC impaired attentional performance, particularly for lesioned animals. These findings suggest that NDMC may functionally decrease acetylcholine stimulation of M1 receptors or that the actions of NDMC at other receptor sites disrupt any beneficial effects of NDMC at the M1 receptor.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Kucinski AJ, De Jong IEM, Sarter M (2016) Preventing falls in PD in a rat model of impaired cognitive control of complex movements by a pro-cholinergic combination treatment. Neuroscience 2016 Abstracts 835.15 / III34. Society for Neuroscience, San Diego, CA.

Summary: Parkinson’s disease (PD) patients, in addition to primary motor symptoms resulting from extensive losses of striatal dopamine (DA), suffer from an interrelated group of motor-control symptoms including postural instability, gait deficits, and a propensity for falls. These levodopa-insensitive symptoms are associated with losses of cortically-projecting cholinergic neurons of the basal forebrain (BF), as well as cognitive impairments such as poor attention. Given the high prevalence and severe consequences of falls in levodopa-treated patients, alternative treatment options are urgently needed. To assess potential treatments we have developed behavioral models of falls in rats including a test system (Michigan Complex Motor Control Task, MCMCT) that requires persistent control of gait, limb coordination, and carefully timed and placed steps during traversals of dynamic surfaces (rotating square rods). Rats with bilateral cholinergic lesions of the BF using 192 IgG-saporin and 6-OHDA lesions to the dopaminergic dorsomedial striatum (dual lesions, DL) exhibit falls while traversing rotating rods and these falls correlate with impaired performance of a sustained attention task. DL rats’ falls have been hypothesized to result from interactions between disruption of normally cholinergically-driven transfer of extero- and interoceptive cue information from cortex to striatum and impaired striatal action sequencing. Here we tested the hypothesis that falls are reduced by co-treatment with acetylcholinesterase inhibitor donepezil and a 5-HT6 receptor antagonist. This combination treatment was previously reported to exhibit synergistic pro-cholinergic activity in rats and improved cognition in patients with moderate Alzheimer’s disease. Overall, drug-treated rats fell less frequently from the rotating rods and were particularly more efficient at reinstating forward movement after sudden stoppages of forward movement with a passive (doorframe) distractor task. This treatment combination may benefit fall propensity in PD patients via maintaining planned movement sequences in working memory and improving the vigor of executing such movements following brief periods of freezing of gait. The neuropharmacological interactions of this treatment may involve diverse signaling pathways converging onto striatal output neurons. Results from current experiments using microdialysis and HPLC-mass spectrometry to simultaneously assess release of striatal ACh, animo acids and monoamines during rotating rod traversals will assist in elucidating potential targets for therapeutic prevention of falls. Supported by a grant from H. Lundbeck A/S

Related Products: 192-IgG-SAP (Cat. #IT-01)