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2013 Targeting Trends Review

62 entries

GABAergic terminals are a source of galanin to modulate cholinergic neuron development in the neonatal forebrain.

Keimpema E, Zheng K, Barde SS, Berghuis P, Dobszay MB, Schnell R, Mulder J, Luiten PG, Xu ZD, Runesson J, Langel U, Lu B, Hokfelt T, Harkany T (2014) GABAergic terminals are a source of galanin to modulate cholinergic neuron development in the neonatal forebrain. Cereb Cortex 24(12):3277-3288. doi: 10.1093/cercor/bht192

Summary: In this work the authors sought to clarify the role of galanin during brain development. Several different techniques were used including the use of Galanin-SAP (Cat. #IT-34) on primary cell cultures from the fetal forebrains of rats. Cultured basal forebrain neurons were exposed to 5 ng/ml of Galanin-SAP for 8 hours, and cell death was assessed after 72 hours. Cholinergic cells were killed by Galanin-SAP, indicating that these neurons can use extracellular galanin-2 receptors to facilitate development.

Related Products: Galanin-SAP (Cat. #IT-34)

Immunolesion-induced loss of cholinergic projection neurones promotes beta-amyloidosis and tau hyperphosphorylation in the hippocampus of triple-transgenic mice.

Hartig W, Saul A, Kacza J, Grosche J, Goldhammer S, Michalski D, Wirths O (2014) Immunolesion-induced loss of cholinergic projection neurones promotes beta-amyloidosis and tau hyperphosphorylation in the hippocampus of triple-transgenic mice. Neuropathol Appl Neurobiol 40(2):106-120. doi: 10.1111/nan.12050

Summary: 3xTg transgenic mice were treated with 2 μg of mu p75-SAP (Cat. #IT-16) into the right lateral ventricle to eliminate cholinergic neurons in the basal forebrain. These mice already have age-dependent β-amyloidosis and tau hyperphosphorylation. This new model supplies a potential framework in which to study the entire pathology of Alzheimer’s disease.

Related Products: mu p75-SAP (Cat. #IT-16)

Medial septal cholinergic neurons modulate isoflurane anesthesia.

Tai SK, Ma J, Leung LS (2014) Medial septal cholinergic neurons modulate isoflurane anesthesia. Anesthesiology 120(2):392-402. doi: 10.1097/ALN.0b013e3182a7cab6

Summary: General anesthesia is associated with a decrease in cholinergic function. This work examines the effect of volatile anesthetics such as isoflurane or ketamine in the context of cholinergic depletion. Rats received 105-ng bilateral injections of 192-IgG-SAP (Cat. #IT-01) into the medial septum. Anesthetic effects were evaluated using a loss of righting reflex test. There was no difference between lesioned and control groups in the response to ketamine. When treated with isoflurane, lesioned animals were affected for longer periods of time, and hippocampal response was reduced. The results suggest a role for septal cholinergic neurons in the sensitivity to isoflurane.

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

C1 neurons: the body’s EMTs.

Guyenet PG, Stornetta RL, Bochorishvili G, Depuy SD, Burke PG, Abbott SB (2013) C1 neurons: the body’s EMTs. Am J Physiol Regul Integr Comp Physiol 305(3):R187-204 . doi: 10.1152/ajpregu.00054.2013

Summary: Although mainly known for their involvement in the control of arterial pressure, C1 neurons are also suspected to participate in numerous other physiological processes such as neuroendocrine response, glucose homeostasis, food consumption, and others. This review discusses the role of these neurons as ’emergency medical technicians’ – cells that produce and modulate physiological survival responses to acute physical stress. The use of Anti-DBH-SAP (Cat. #IT-03) to delineate C1 neurons in the rostral ventrolateral aspect of the medulla oblongata is discussed.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Reduction in cholinergic interneuron density in the nucleus accumbens attenuates local extracellular dopamine release in response to stress or amphetamine.

Laplante F, Dufresne MM, Ouboudinar J, Ochoa-Sanchez R, Sullivan RM (2013) Reduction in cholinergic interneuron density in the nucleus accumbens attenuates local extracellular dopamine release in response to stress or amphetamine. Synapse 67(1):21-29. doi: 10.1002/syn.21612

Summary: The authors examined whether excessive dopamine neurotransmission in the mesolimbic system is due to higher levels of presynaptic or postsynaptic dopamine. Rats received 250-ng bilateral injections of anti-ChAT-SAP (Cat. #IT-42) into the nucleus accumbens. Rabbit IgG-SAP (Cat. #IT-35) was used as a control. The data suggest that reduction of cholinergic interneurons in the nucleus accumbens suppresses presynaptic dopamine release.

Related Products: Anti-ChAT-SAP (Cat. #IT-42), Rabbit IgG-SAP (Cat. #IT-35)

Read the featured article in Targeting Trends.

Leptin-sensitive neurons in the arcuate nucleus integrate activity and temperature circadian rhythms and anticipatory responses to food restriction.

Wiater MF, Li AJ, Dinh TT, Jansen HT, Ritter S (2013) Leptin-sensitive neurons in the arcuate nucleus integrate activity and temperature circadian rhythms and anticipatory responses to food restriction. Am J Physiol Regul Integr Comp Physiol 305(8):R949-R960. doi: 10.1152/ajpregu.00032.2013

Summary: The arcuate nucleus (Arc) of the hypothalamus is known to participate in the regulation of feeding, adiposity, and leptin-dependent metabolism. The authors examined the role of leptin-receptive neurons in locomotor and temperature rhythms. Rats received four bilateral injections of Leptin-SAP (Cat. #IT-47) into the Arc; Blank-SAP (Cat. #IT-21) was used as a control. The lesion affected learning connected to light cycles, but not learning connected to food schedules, suggesting a mechanism for internal desynchrony that might play a role in obesity and other metabolic disorders.

Related Products: Leptin-SAP (Cat. #IT-47), Blank-SAP (Cat. #IT-21)

Loss of neurons in rostral ventromedial medulla that express neurokinin-1 receptors decreases the development of hyperalgesia.

Khasabov SG, Simone DA (2013) Loss of neurons in rostral ventromedial medulla that express neurokinin-1 receptors decreases the development of hyperalgesia. Neuroscience 250C:151-165. doi: 10.1016/j.neuroscience.2013.06.057

Summary: Previous data has indicated that neurokinin-1 receptors are located on ON cells in the rostral ventromedial medulla (RVM). ON cells are considered pronociceptive because noxious stimulation is stimulatory. In this work the authors eliminated ON cells using 0.3-μl injections of 1 μM SSP-SAP (Cat. #IT-11) into the left and right side of the RVM. Blank-SAP (Cat. #IT-21) was used as a control. SSP-SAP treatment did not change mechanical or heat withdrawal responses, or change morphine-induced analgesia. A significant reduction in the duration of nocifensive behaviors induced by various hyperalgesic stimulators indicated that these neurons are involved in pain facilitation rather than modulation.

Related Products: SSP-SAP (Cat. #IT-11), Blank-SAP (Cat. #IT-21)

Selective immunotoxic lesions of basal forebrain cholinergic neurons: twenty years of research and new directions.

Baxter MG, Bucci DJ (2013) Selective immunotoxic lesions of basal forebrain cholinergic neurons: twenty years of research and new directions. Behav Neurosci 127(5):611-618 . doi: 10.1037/a0033781

Summary: This review covers twenty years of basal forebrain cholinergic lesioning. The initial use of 192-IgG-SAP (Cat. #IT-01) is discussed, as well as other immunotoxins such as GAT-1-SAP (Cat. #IT-32) and OX7-SAP (Cat. #IT-02). The findings generated by the use of 192-IgG-SAP and how those data have helped forward the understanding of how the cholinergic system functions in the basal forebrain are detailed. The authors also discuss new directions in the field.

Related Products: 192-IgG-SAP (Cat. #IT-01), OX7-SAP (Cat. #IT-02), GAT1-SAP (Cat. #IT-32)

Noggin and Sonic hedgehog are involved in compensatory changes within the motoneuron-depleted mouse spinal cord.

Gulino R, Gulisano M (2013) Noggin and Sonic hedgehog are involved in compensatory changes within the motoneuron-depleted mouse spinal cord. J Neurol Sci 332(1-2):102-109. doi: 10.1016/j.jns.2013.06.029

Summary: Noggin (NOG) and Sonic hedgehog (Shh) are both involved in the generation and organization of neural tissues. In order to clarify the role of these two proteins in the regulation of neurogenesis and/or neuroplasticity the authors used a motoneuron depletion model in the mouse spinal cord. 3 μg of CTB-SAP (Cat. #IT-14) was injected into each of the medial and lateral gastrocnemius muscles and the expression of NOG and Shh were monitored. Motor performance also correlated with NOG and Shh levels, indicating that these proteins could play roles in regeneration and functional restoration.

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

Neurotrophic factors rescue basal forebrain cholinergic neurons and improve performance on a spatial learning test.

Lee YS, Danandeh A, Baratta J, Lin CY, Yu J, Robertson RT (2013) Neurotrophic factors rescue basal forebrain cholinergic neurons and improve performance on a spatial learning test. Exp Neurol 249C:178-186. doi: 10.1016/j.expneurol.2013.08.012

Summary: It is thought that therapeutic treatments of the cholinergic system may be a viable treatment for Alzheimer’s disease. In order to examine this hypothesis the authors administered a total of 160 ng of 192-IgG-SAP (Cat. #IT-01) in the form of bilateral injections into the medial septum. The lesioned animals then received 4-week infusions of nerve growth factor, neurotrophin 3, or both into the lateral ventricles. Animals treated with any neurotrophin, either alone or as a combination, retained more ChAT-positive neurons and performed better on a delayed match-to-position task than control animals. The data strengthen the theory that exogenous neurotrophic factors ameliorate the effects of Alzheimer’s disease.

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

Implication of cerebral dopamine-beta hydroxylase for cardiovascular and mood regulation in rats.

Chang ST, Liu YP, Huang CL, Wang PY, Tung CS (2013) Implication of cerebral dopamine-beta hydroxylase for cardiovascular and mood regulation in rats. Chin J Physiol 56(4):209-218. doi: 10.4077/CJP.2013.BAB103

Summary: The ascending fibers affected by norepinephrine are involved in a variety of processes, including emotion, anxiety, and regulation of central autonomic outflows such as cardiovascular regulation and energy balance. The authors examined whether the loss of norephinephrine would cause autonomic failure in cardiovascular regulation. Rats received a single intraventricular injection of anti-DBH-SAP (Cat. #IT-03). Saporin (Cat. #PR-01) was used as a control. The results demonstrate that norepinephrine deficits in the brain influence reduction of excitatory responses to orthostatic stress.

Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01)

BB2 bombesin receptor-expressing spinal neurons transmit herpes-associated itch by BB2 receptor-independent signaling.

Sasaki A, Adhikari S, Andoh T, Kuraishi Y (2013) BB2 bombesin receptor-expressing spinal neurons transmit herpes-associated itch by BB2 receptor-independent signaling. Neuroreport 24(12):652-656. doi: 10.1097/WNR.0b013e32836352d8

Summary: Using a skin rash model created by inoculating mice with human herpes virus, bombesin receptor-expressing spinal neurons were lesioned intrathecally with 400 ng of Bombesin-SAP (Cat. #IT-40). Lesioned animals displayed reduced scratching, but licking (due to pain) was not reduced.

Related Products: Bombesin-SAP (Cat. #IT-40), Blank-SAP (Cat. #IT-21)

Cortical metabolic deficits in a rat model of cholinergic basal forebrain degeneration.

Gelfo F, Petrosini L, Graziano A, De Bartolo P, Burello L, Vitale E, Polverino A, Iuliano A, Sorrentino G, Mandolesi L (2013) Cortical metabolic deficits in a rat model of cholinergic basal forebrain degeneration. Neurochem Res 38(10):2114-2123. doi: 10.1007/s11064-013-1120-2

Summary: In this work the authors investigated the connection between cholinergic depletion caused by conditions such as Alzheimer’s disease and cerebral energy metabolism deficits. Rats received a 0.4-μg injection of 192-IgG-SAP (Cat. #IT-01) into the nucleus basalis magnocellularis. Neuronal metabolic activity was measured by assaying cytochrome oxidase (CO) activity. The unilateral injection produced a bilateral deficit in CO activity throughout the cortex, and the front and parietal cortices showed CO deficits before the lesion was complete. The data suggest a link between cholinergic hypofunctionality and metabolic deficit.

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

Photochemical internalization (PCI) of immunotoxins targeting CD133 is specific and highly potent at femtomolar levels in cells with cancer stem cell properties.

Bostad M, Berg K, Hogset A, Skarpen E, Stenmark H, Selbo PK (2013) Photochemical internalization (PCI) of immunotoxins targeting CD133 is specific and highly potent at femtomolar levels in cells with cancer stem cell properties. J Control Release 168(3):317-326. doi: 10.1016/j.jconrel.2013.03.023

Summary: Targeted therapies for cancer can be trapped in the lysosome and compartmentalized away from the target. Photochemical internalization is a method to increase the efficacy of these compounds by releasing the therapeutic portion of the molecule from the endocytic vesicles to the cytosol by the use of light. The authors demonstrate this method on cells expressing the cancer stem cell marker CD133. Biotinylated antibodies against CD133 were combined with Streptavidin-ZAP (Cat. #IT-27) and applied to cell lines.

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

A novel model for evaluating therapies targeting human tumor vasculature and human cancer stem-like cells.

Burgos-Ojeda D, McLean K, Bai S, Pulaski H, Gong Y, Silva I, Skorecki K, Tzukerman M, Buckanovich RJ (2013) A novel model for evaluating therapies targeting human tumor vasculature and human cancer stem-like cells. Cancer Res 73(12):3555-3565. doi: 10.1158/0008-5472.CAN-12-2845

Objective: To evaluate tumor vascular markers (TVM) expression in a human embryonic stem cell–derived teratoma (hESCT) tumor model previously shown to have human vessels.

Summary: The model tested represents a useful tool to test anti-human TVM therapy and evaluate in vivo human CSC tumor biology.

Usage: In vitro – Anti-THY1-SAP (biotinylated Anti-THY1 mixed equimolar with Streptavidin-ZAP) was incubated with mesenchymal stem cells (MSC); resulting in statistically significant MSC death. In vivo – Anti-THY1-SAP or control (Rat IgG-SAP) was administered intravenously. Treated ovarian tumors showed delayed growth and significant reduction in central tumor viability.

Related Products: Streptavidin-ZAP (Cat. #IT-27), Rat IgG-SAP (Cat. #IT-17)

Time course study of targeted ablation of KNDy neurons, but not tyrosine-hydroxylase neurons, in the rat arcuate nucleus using a neurokinin b-saporin.

Helena CV, Kalil B, Anselmo-Franci JA, Bertram R (2013) Time course study of targeted ablation of KNDy neurons, but not tyrosine-hydroxylase neurons, in the rat arcuate nucleus using a neurokinin b-saporin. Endocr Rev 34:OR47-5. 95th Annual Meetin and Expo, San Francisco. doi: 10.1093/edrv/34.supp.1

Summary: Ovariectomized rats were given bilateral injections of NK3-SAP (Cat. #IT-63) into the arcuate nucleus for a time course study of KNDy neuron loss. Blank-SAP (Cat. #IT-21) was used as a control.

Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)

P2Y1 receptors expressed by C1 neurons determine peripheral chemoreceptor modulation of breathing, sympathetic activity, and blood pressure.

Wenker IC, Sobrinho CR, Takakura AC, Mulkey DK, Moreira TS (2013) P2Y1 receptors expressed by C1 neurons determine peripheral chemoreceptor modulation of breathing, sympathetic activity, and blood pressure. Hypertension 62(2):263-273. doi: 10.1161/HYPERTENSIONAHA.113.01487

Summary: Peripheral chemoreceptor activation response is mediated by catecholaminergic C1 cells in the rostral ventrolateral medulla (RVLM). The authors investigated the molecular mechanisms linking this drive to increased sympathetic activity and hypertension through a variety of methods, including lesioning C1 cells in the RVLM. Rats received 4.2-ng bilateral injections of Anti-DBH-SAP (Cat. #IT-03) into the RVLM. Comparison of lesioned animals to controls demonstrated that P2Y1 receptors on C1 cells in the RVLM are key components in the regulation of breathing, sympathetic nerve activity, and blood pressure.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

An environment-dependent modulation of cortical neural response by forebrain cholinergic neurons in awake rat.

Ariffin MZ, Chang LS, Koh HC, Low CM, Khanna S (2013) An environment-dependent modulation of cortical neural response by forebrain cholinergic neurons in awake rat. Brain Res 1513:72-84. doi: 10.1016/j.brainres.2013.03.046

Summary: Rats received 168 ng of 192-IgG-SAP (Cat. #IT-01) into the medial septum and induction of c-Fos expression in response to either familiar or novel stimuli was measured.

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

Neurotrophin receptor p75 mediates the uptake of the amyloid beta (Abeta) peptide, guiding it to lysosomes for degradation in basal forebrain cholinergic neurons.

Ovsepian SV, Antyborzec I, O’Leary VB, Zaborszky L, Herms J, Oliver Dolly J (2013) Neurotrophin receptor p75 mediates the uptake of the amyloid beta (Abeta) peptide, guiding it to lysosomes for degradation in basal forebrain cholinergic neurons. Brain Struct Funct 219(5):1527-1541. doi: 10.1007/s00429-013-0583-x

Summary: Accumulation of β-amyloid in the brain is considered one of the main causes of Alzheimer’s disease. The increase in β-amyloid is accompanied by a reduction in levels of the high affinity nerve growth factor receptor (trkA) and cognitive impairment. The authors looked at levels of the low affinity nerve growth factor receptor (p75) that do not decline. Using a 0.8-μg injection of 192-Cy3 (Cat. #FL-01) into the medial prefrontal cortex of rats the authors assessed the transport of p75 and β-amyloid by microscopy. The results indicate that the primary destinations of both p75 and β-amyloid were the late endosome and lysosome.

Related Products: 192-IgG Mouse Monoclonal, Cy3-labeled (Cat. #FL-01)

Cholinergic basal forebrain structures are involved in the mediation of the arousal effect of noradrenaline.

Lelkes Z, Porkka-Heiskanen T, Stenberg D (2013) Cholinergic basal forebrain structures are involved in the mediation of the arousal effect of noradrenaline. J Sleep Res 22(6):721-726. doi: 10.1111/jsr.12061

Summary: Wakefulness is enhanced by the injection of noradrenaline into the basal forebrain, but it has not been clear whether cholinergic or non-cholinergic neurons are involved. 230 ng of 192-IgG-SAP (Cat. #IT-01) was administered to the horizontal diagonal band/substantia innominata/ magnocellular preoptic nucleus of rats. Upon treatment with methoxamine, lesioned animals lost the non-REM sleep-suppressing effect, but the REM sleep-suppressing effect remained intact.

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

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