References

Gulisano M, Vicario N, Costantino A, Giunta MAS, Spitale FM, Parenti R, Gulino R (2018) Sonic hedgehog signalling pathway during regenerative processes in a mouse model of spinal motoneuronal loss. Neuroscience 2018 Abstracts 379.29 / L1. Society for Neuroscience, San Diego, CA.

Summary: Background – Neuronal loss represents the consequence of direct or indirect insults to neurons, as well as one of the major factors mediating persistent disability. Gliosis, neuroinflammation and neurodegeneration are processes in which different cell populations have an interplay mediating both hostile microenvironment and self-repairing mechanisms. Sonic hedgehog (Shh) signaling, which has been indicated as an important pathway in central nervous system development and neural stem cells (NSCs) function, may have a role in prompting the repairing and modulating actions of endogenous and/or exogenous NSCs in neurodegenerative conditions. Methodology – Somatic NSCs were obtained from the subventricular zone (SVZ) of 8 week old female 129/Sv mice. We studied the Shh pathway on NSCs both in vitro and in a mouse model of spinal motorneuronal degeneration induced by cholera toxin B conjugated to saporin (CTB-Sap) injection into the gastrocnemius muscle. Results – NSCs were derived, expanded and characterized in vitro. We analyzed the effects of Shh signaling pathway modulation on NSCs in vitro, finding a significant increase of the NSCs growth rate (2.98±0.58 vs. 5.26±0.57, p<0.05) and neurospheres diameters (109.9±2.4μm vs. 129.6±3.7μm, p<0.01) upon Shh pathway activation. We then characterized Shh signaling activation in CTB-Sap mice analyzing neuronal loss, gliosis, inflammation and compensatory self-repairing mechanisms, compared to intact control mice. Conclusions - Our results suggest a crucial role of Shh signaling during regenerative processes and NSCs as a potential strategy to support recovery after spinal motoneuronal degeneration, thus representing a promising approach for neurodegenerative disorders.

Related Products: CTB-SAP (Cat. #IT-14)

Cammarata C, DeRosa ED, Anderson AK (2018) Lifespan and cholinergic changes in cognitive flexibility in rats. Neuroscience 2018 Abstracts 512.05 / GGG8. Society for Neuroscience, San Diego, CA.

Summary: The ability to update one’s mental schemas in order respond flexibly and adaptably – i.e. cognitive flexibility – is crucial to navigating a dynamic environment. Proactive interference (PI) is a phenomenon wherein prior memory impedes the formation of new memories for similar information, biasing behavior toward no-longer-relevant schemas. Thus, overcoming PI is an important aspect of cognitive flexibility. PI is exacerbated during aging, and in turn contributes to age-related deficits in cognitive flexibility. In young animals and young adult humans, resolution of PI has been found to rely on neuromodulatory activity via Acetylcholine (ACh), and ACh levels are known to decline in aging, however it has yet to be demonstrated whether these age-related changes in ACh directly contribute to age-related increase in PI. Here, we first compared PI resolution in middle-aged (13 months, n = 8) and old (23 months, n= 11) male Long Evans rats, finding that old animals were more inefficient in resolving PI when compared to the middle-aged animals. Furthermore we performed cholinergic deafferentation, with the immunotoxin 192-IgG saporin (SAP; 0.2 µl of 0.3 µg/µl dissolved in sterile phosphate buffered sale in each of four locations targeting bilateral anterior and posterior basal forebrain), in our older rats (N= 5 SAP and N=6 Sham) which had no effect on the floor performance of older rats. This suggests that the inability to resolve PI seen in the aged rats may be due to already-depleted levels of ACh. We are currently collecting local field potential data in the prelimbic and posterior parietal cortices in behaving older and younger rats and will combine this with central administration of muscarinic cholinergic pharmacology to continue to examine age-related changes in the cortical dynamics that support cognitive flexibility. Based on prior findings in our laboratory examining similar attentional flexibility, we predict the young animals will demonstrate increased beta band LFP activity in the posterior parietal cortex, and potentially increased beta coherence between prefrontal and posterior parietal cortices, related to successful resolution of PI. We expect such activity to be mitigated by cholinergic antagonists and in the older animals.

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

Zoccal DB, Silva JN, Barnett WH, Lemes EV, Falquetto B, Colombari E, Molkov YI, Moreira TS, Takakura AC (2018) Interaction between the retrotrapezoid nucleus and the parafacial respiratory group to regulate active expiration and sympathetic activity in rats. Am J Physiol Lung Cell Mol Physiol 315(5):L891-L909. doi: 10.1152/ajplung.00011.2018

Objective: To investigate the microcircuitry responsible for the distribution of the excitatory signals to the the parafacial respiratory group (pFRG) and the the respiratory central pattern generator (rCPG) in conditions of high CO2.

Summary: The activation of the pFRG late-E neurons during hypercapnia require glutamatergic inputs from the RTN neurons that intrinsically detect changes in CO2/pH.

Usage: Bilateral injections of SSP-SAP (0.6 ng in 100 nL of saline per side).

Related Products: SSP-SAP (Cat. #IT-11)

Qian L, Milne MR, Shepheard S, Rogers ML, Medeiros R, Coulson EJ (2019) Removal of p75 neurotrophin receptor expression from cholinergic basal forebrain neurons reduces amyloid-β plaque deposition and cognitive impairment in aged APP/PS1 mice. Mol Neurobiol 56(7):4639-4652. doi: 10.1007/s12035-018-1404-2

Objective: To investigate the contribution of CBF neuronal p75NTR to the progression of Alzheimer’s Disease

Summary: Data indicate that a direct interaction between CBF-expressed p75NTR and Aβ does not contribute significantly to the regulation of Aβ load.

Usage: To lesion CBF neurons, a single infusion of mu p75-SAP or control Rabbit IgG-SAP (0.4 mg/ml) was stereotaxically-injected into the basal forebrain.

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

Garrett AM, Khalil A, Walton DO, Burgess RW (2018) DSCAM promotes self-avoidance in the developing mouse retina by masking the functions of cadherin superfamily members. Proc Natl Acad Sci U S A 115:E10216-E10224. doi: 10.1073/pnas.1809430115

Summary: Focus on DSCAM (Down syndrome cell adhesion molecule 1) self-avoidance function in the mouse retina. DSCAM and members of the cadherin superfamily have also emerged as key contributors to a variety of neurodevelopmental disorders, including autism, schizophrenia, bipolar disease, Down syndrome and intellectual disability.

Related Products: Melanopsin-SAP (Cat. #IT-44)

Han W, Tellez LA, Perkins MH, Perez IO, Qu T, Ferreira J, Ferreira TL, Quinn D, Liu Z-W, Gao X-B, Kaelberer MM, Bohórquez DV, Shammah-Lagnado SJ, de Lartigue G, de Araujo IE (2018) A neural circuit for gut-induced reward. Cell 175:665-678. doi: 10.1016/j.cell.2018.08.049

Objective: To determine relevant gut-brain neuronal circuitry to motivational and emotional states.

Summary: There is a critical role for the vagal gut-to-brain axis in motivation and reward.

Usage: Injected 0.5 µl of CCK-SAP (250 ng/µl) into the R-NG of VGlut2-ires-Cre mice.

Related Products: CCK-SAP (Cat. #IT-31)

Acharjee S, Verbeek M, Gomez CD, Bisht K, Lee B, Benoit L, Sharkey KA, Benediktsson A, Tremblay M-E, Pittman QJ (2018) Reduced microglial activity and enhanced glutamate transmission in the basolateral amygdala in early CNS autoimmunity. J Neurosci 38:9019-9033. doi: 10.1523/JNEUROSCI.0398-18.2018

Objective: To identify CNS changes associated with behaviors in multiple sclerosis (MS) patients.

Summary: The data from this study reveal increased synaptic activity and spine density in early stages of experimental autoimmune encephalomyelitis (an animal model of MS) in the basolateral amygdala.

Usage: Mac-1-SAP mouse/human or Rat-IgG-SAP (control) was injected unilaterally in the BLA (1 ug/1 ul).

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06), Rat IgG-SAP (Cat. #IT-17)

Lind LA, Murphy ER, Lever TE, Nichols NL (2018) Hypoglossal motor neuron death via intralingual CTB-saporin (CTB-SAP) injections mimic aspects of amyotrophic lateral sclerosis (ALS) related to dysphagia. Neuroscience 390:303-316. doi: 10.1016/j.neuroscience.2018.08.026

Objective: Despite its fundamental importance, dysphagia (difficulty swallowing) and strategies to preserve swallowing function have seldom been studied in ALS models.

Summary: The authors report a novel experimental model using intralingual injections of cholera toxin B conjugated to saporin (CTB-SAP) to study the impact of only hypoglossal motor neuron death without the many complications that are present in ALS models.

Usage: Hypoglossal motor neuron survival, swallowing function, and hypoglossal motor output were assessed in Sprague Dawley rats after intralingual injection of either CTB-SAP (25 ug) or unconjugated CTB and SAP (controls) into the genioglossus muscle.

Related Products: CTB-SAP (Cat. #IT-14)

Ebadi R, Kordi-Tamandani DM, Ghaedi K, Nasr-Esfahani MH (2018) Comparison of two different media for maturation rate of neural progenitor cells to neuronal and glial cells emphasizing on expression of neurotrophins and their respective receptors. 45(6):2377-2391. doi: 10.1007/s11033-018-4404-4 PMID: 30306506

Objective: To compare neural differentiation potential of two different media, NB + 5%ES-FBS + N2B27 and Ko-DMEM + 5%ES-FBS for conversion of mESC derived neural progenitors (NPs) into mature neural cells with emphasis on effect of these two media on neurotrophins and their respective receptors expression.

Summary: Results indicated that NB + 5%ES-FBS + N2B27 medium promoted neural differentiation process of mESCs and caused enhancement of neurotrophins protein expression in addition to their cognate receptors.

Usage: Western Blot (1:4000)

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

Mao S, Wang L, Chen P, Lan Y, Guo R, Zhang M (2018) Nanoparticle-mediated delivery of Tanshinone IIA reduces adverse cardiac remodeling following myocardial infarctions in a mice model: Role of NF-κB pathway. Artif Cells Nanomed Biotechnol 46(sup3):S707-S716. doi: 10.1080/21691401.2018.1508028 PMID: 30284484

Objective: To develop a nanoparticle-mediated drug delivery system for Tanshinone IIA.

Summary: Demonstrated a novel delivery mechanism of a therapeutic agent, tanshinone IIA-NP, which prevented IκB phosphorylation and subsequent NF-κB activation resulting in the suppression of inflammatory responses and reduction of cardiomyocytes apoptosis and fibrotic process, contributing to the mitigation of LV remodeling and improvement of cardiac functions following MI.

Usage: Immunoblotting analysis for the activation of AT-1R on an ischemic border zone 4 weeks after explosion to coronary artery ligation.

Related Products: Angiotensin II receptor (AT-1R) Rabbit Polyclonal, affinity-purified (Cat. #AB-N27AP)