2012 Targeting Trends Review

Kaminski KL, Watts AG (2012) Intact catecholamine inputs to the forebrain are required for appropriate regulation of corticotrophin-releasing hormone and vasopressin gene expression by corticosterone in the rat paraventricular nucleus. J Neuroendocrinol 24(12):1517-1526. doi: 10.1111/j.1365-2826.2012.02363.x

Summary: Corticosterone releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus (PVH) control release of adrenocorticotropic hormone and glucocorticoids. In order to determine the contribution of these neurons to CRH and vasopressin expression in the PVH the authors administered bilateral 42 ng injections of anti-DBH-SAP (Cat. #IT-03) into the PVH of both normal and adrenalectomized rats. Mouse IgG-SAP (Cat. #IT-18) was used as a control. The data demonstrate that under certain conditions CRH and vasopressin gene expression is modulated by interactions between corticosterone and catecholaminergic projections to the hypothalamus.

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

Daubert DL, McCowan M, Erdos B, Scheuer DA (2012) Nucleus of the solitary tract catecholaminergic neurons modulate the cardiovascular response to psychological stress in rats. J Physiol 590(Pt 19):4881-4895. doi: 10.1113/jphysiol.2012.232314

Summary: It has been proposed that the nucleus of the solitary tract (NTS) is highly involved in cardiovascular regulation. In light of the fact that catecholaminergic neurons in the NTS are part of stress-related neurocircuitry, the authors investigated whether these neurons attenuate blood pressure increases due to stress. Rats received 22 ng bilateral injections of anti-DBH-SAP (Cat. #IT-03) into the NTS. Mean arterial pressure and baseline plasma epinephrine were measured in a restraint test. Animals lesioned with anti-DBH-SAP displayed a significantly enhanced mean arterial pressure, and reduced plasma epinephrine. These data suggest that catecholaminergic neurons in the NTS inhibit the arterial pressure response to stress, but maintain the corticosteroid response.

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

Paolone G, Lee TM, Sarter M (2012) Time to pay attention: attentional performance time-stamped prefrontal cholinergic activation, diurnality, and performance. J Neurosci 32(35):12115-12128. doi: 10.1523/JNEUROSCI.2271-12.2012

Summary: This work examined the role that neuronal mechanisms have in cognitive performance on a fixed-time task. The authors performed bilateral 160 ng infusions of 192-IgG-SAP (Cat. #IT-01) into the nucleus basalis and substantia innominata of the basal forebrain of rats that had reached stable performance on a sustained attention task. In control animals trained in the same task, prefrontal cholinergic neurotransmission persisted at the fixed time even after the task was terminated. Both lesioning and altering the task training time impaired task performance.

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

Kirillova V, Prosviryakov E (2012) Disrupted serotonergic system in patients with pulmonary hypertension may serve as novel biomarkers new therapeutic targets and to assess severity, progression and response to treatment. Cardiovasc Res 93 Suppl 1:P209. European Society of Cardiology, Munich Germany. PMID: 909090

Summary: At the Frontiers in Cardiovascular Biology meeting in London the authors presented work examining the role serotonin and serotonin transporters play in pulmonary hypertension. Anti-SERT (Cat. #AB-N09, 1:500) was used in immunohistochemistry to detect the serotonin transporter in the myocardium.  The data demonstrate that serotonin levels in the blood and serotonin transporter levels in the myocardium are both increased in patients with pulmonary hypertension.

Related Products: Antibody to Serotonin Transporter (SERT, Cat. #AB-N09)

Koppen JR, Winter SS, Stuebing SL, Cheatwood JL, Wallace DG (2013) Infusion of GAT1-saporin into the medial septum/vertical limb of the diagonal band disrupts self-movement cue processing and spares mnemonic function. Brain Struct Funct 218(5):1099-1114. doi: 10.1007/s00429-012-0449-7

Summary: Both mnemonic and spatial processing are adversely affected by dementia due to Alzheimer’s disease. There is evidence to support the involvement of cholinergic systems in this deficit. In this work the authors examined how GABAergic neurons in the septohippocampus contribute to these cognitive functions. Rats received a total of 350 ng of GAT-1-SAP (Cat. #IT-32) infused into the medial septum-diagonal band of Broca. Although lesioned animals performed normally in tasks involving spatial cues, food hoarding was affected indicating that self-movement cue processing was interfered with by the loss of these GABAergic neurons.

Related Products: GAT1-SAP (Cat. #IT-32)

Savage S, Mattsson A, Olson L (2012) Cholinergic denervation attenuates phencyclidine-induced c-fos responses in rat cortical neurons. Neuroscience 216:38-45. doi: 10.1016/j.neuroscience.2012.04.064

Summary: Phenylcyclidine (PCP) has been used to model aspects of schizophrenia in animals. 81 ng of 192-IgG-SAP (Cat. #IT-01) was injected into the nucleus basalis magnocellularis of rats to assess the effects of low dose PCP in a cholinergically-deprived system. Saporin (Cat. #PR-01) was used as a control. Results demonstrate basalocortical cholinergic neurons are necessary for PCP to have full effect.

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

Gil-Bea FJ, Gerenu G, Aisa B, Kirazov LP, Schliebs R, Ramirez MJ (2012) Cholinergic denervation exacerbates amyloid pathology and induces hippocampal atrophy in Tg2576 mice. Neurobiol Dis 48(3):439-446. doi: 10.1016/j.nbd.2012.06.020

Summary: The hallmarks of Alzheimer’s disease (AD) include hippocampal cell loss, cholinergic dysfunction, amyloid plaques, and neurofibrillary tangles, among other things. This work sought to examine the interaction between cholinergic denervation, amyloid precursor protein (APP) processing, and hippocampal integrity. Tg2576 transgenic mice received 2 μg of mu p75-SAP (Cat. #IT-16) injected into the third ventricle. These mice overexpress a version of human APP. Lesioned animals displayed various aspects of AD such as hippocampal synaptic pathology and neurodegeneration, indicating that immunolesions in this mouse line produce a viable model for AD.

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

Parent M, Bedard MA, Aliaga A, Soucy JP, Landry St-Pierre E, Cyr M, Kostikov A, Schirrmacher E, Massarweh G, Rosa-Neto P (2012) PET imaging of cholinergic deficits in rats using [(18)F]fluoroethoxybenzovesamicol ([(18)F]FEOBV). Neuroimage 62(1):555-561. doi: 10.1016/j.neuroimage.2012.04.032

Summary: In order to better understand and evaluate neurodegenerative diseases imaging agents are necessary to visualize the affected systems. [18F]fluoroethoxybenzovesamicol ([18F]FEOBV) is one such agent that shows promise for labeling the vesicular acetylcholine transporter with positron emission tomography. The authors injected 0.2 μg of 192-IgG-SAP (Cat. #IT-01) into the left hemisphere of rats to model cholinergic terminal loss as seen in aged animals. Loss of these terminals was found to reduce [18F]FEOBV binding in the ventral frontal cortex on the lesioned side, and also in the homologous region of the contralateral hemisphere, allowing detection of both physiological and pathological reduction of cholinergic terminals.

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

Huang TY, Lin LS, Cho KC, Chen SJ, Kuo YM, Yu L, Wu FS, Chuang JI, Chen HI, Jen CJ (2012) Chronic treadmill exercise in rats delicately alters the Purkinje cell structure to improve motor performance and toxin resistance in the cerebellum. J Appl Physiol 113(6):889-895. doi: 10.1152/japplphysiol.01363.2011

Summary: It is known that exercise can improve motor performance, but the cellular changes that occur in the cerebellum in response to exercise are not understood. Rats were subject to exercise training and a rotarod test was used to evaluate performance. After training some animals were given a 2 μg injection of OX7-SAP (Cat. #IT-02) into the lateral ventricle. In sedentary rats OX7-SAP administration reduced rotarod performance as well as eliminated 60% of Purkinjie cells. Rats given exercise training exhibited much milder injury in the cerebellum as a result of the lesion and maintained a higher level of rotarod performance than the sedentary group.

Related Products: OX7-SAP (Cat. #IT-02)

Laplante F, Zhang ZW, Huppe-Gourgues F, Dufresne MM, Vaucher E, Sullivan RM (2012) Cholinergic depletion in nucleus accumbens impairs mesocortical dopamine activation and cognitive function in rats. Neuropharmacology 63(6):1075-1084. doi: 10.1016/j.neuropharm.2012.07.033

Summary: Current thought is that loss of cholinergic function in the nucleus accumbens (N.Acc) is associated with schizophrenia. This deficit is accompanied by low dopaminergic activity in the prefrontal area, which adversely affects working memory. Rats received bilateral injections totaling 500 ng of anti-ChAT-SAP (Cat. #IT-42) into the N.Acc; rabbit IgG-SAP (Cat. #IT-35) was used as a control. Lesioned animals had markedly reduced mesocortical dopamine activation, which corresponded with cognitive impairments. The data suggest that loss of cholinergic neurons in the N.Acc causes loss of dopamine function in the mesocorticolimbic system.

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

Brown RE, Basheer R, McKenna JT, Strecker RE, McCarley RW (2012) Control of sleep and wakefulness. Physiol Rev 92(3):1087-1187 . doi: 10.1152/physrev.00032.2011

Summary: This review summarizes mechanisms in the brain that control sleep and wakefulness. Areas discussed include wakefulness promoting systems, non-REM sleep and REM sleep definitions, the function of each kind of sleep, and dysfunction that occurs as a result of sleep disruption. Several targeted conjugates are mentioned, such as 192-IgG-SAP (Cat. #IT-01), anti-DBH-SAP (Cat. #IT-03), and orexin-SAP (Cat. #IT-20). The review summarizes the use of these products to better understand sleep networks.

Related Products: 192-IgG-SAP (Cat. #IT-01), Anti-DBH-SAP (Cat. #IT-03), Orexin-B-SAP (Cat. #IT-20)

Sikandar S, Bannister K, Dickenson AH (2012) Brainstem facilitations and descending serotonergic controls contribute to visceral nociception but not pregabalin analgesia in rats. Neurosci Lett 519(1):31-36. doi: 10.1016/j.neulet.2012.05.009

Summary: Neurons in the rostral ventromedial medulla (RVM) are classified as ON, OFF, or NEUTRAL based on firing patterns in response to noxious somatic stimulation. ON cells express μ-opioid receptors, and are therefore a target for dermorphin-SAP (Cat. #IT-12). The authors injected the RVM of rats with 3 pmol of dermorphin-SAP; Saporin (Cat. #PR-01) was used as a control. Results show the μ-opioid receptor population is not needed for the function of analgesics through the serotonergic system.

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Saporin (Cat. #PR-01)

Mishra SK, Holzman S, Hoon MA (2012) A nociceptive signaling role for neuromedin B. J Neurosci 32(25):8686-8695. doi: 10.1523/JNEUROSCI.1533-12.2012

Summary: Previous work suggests that neuromedin B (NMB) is involved in nociception. Direct injection of the peptide causes nociceptive sensitization, while NMB antagonists attenuate sensitization in reponse to nerve stimulation with mustard oil. Specific subsets of dorsal horn interneurons were eliminated by administering either 10 μg of the custom conjugate neuromedin B-SAP, 0.13 μg of SSP-SAP (Cat. #IT-11), or 1.3 μg of bombesin-SAP (Cat. #IT-40). Blank-SAP (Cat. #IT-21) was used as a control. The data indicate that NMB may be involved in the perception of thermal sensation, but not mechanical or pruritic sensation.

Related Products: NMB-SAP (Cat. #IT-70), SSP-SAP (Cat. #IT-11), Bombesin-SAP (Cat. #IT-40), Blank-SAP (Cat. #IT-21)

Abbott SB, Kanbar R, Bochorishvili G, Coates MB, Stornetta RL, Guyenet PG (2012) C1 neurons excite locus coeruleus and A5 noradrenergic neurons along with sympathetic outflow in rats. J Physiol 590(12):2897-2915. doi: 10.1113/jphysiol.2012.232157

Summary: C1 neurons are known to activate sympathetic tone and stimulate the hypothalamic-pituitary-adrenal axis. C1 activation is also reported to inhibit locus coeruleus (LC) neurons. Rats received 0.6 ng of SSP-SAP (Cat. #IT-11) injected under the caudal edge of the facial motor nucleus to destroy the retrotrapezoid nucleus, increasing the proportion of C1 ChR2-expressing neurons. Stimulation of C1 neurons resulted in activation of noradrenergic neurons that are involved in hypoxia and hypotension.

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

Tai SK, Leung LS (2012) Vestibular stimulation enhances hippocampal long-term potentiation via activation of cholinergic septohippocampal cells. Behav Brain Res 232(1):174-182. doi: 10.1016/j.bbr.2012.04.013

Summary: It is known that vestibular stimulation induces acetylcholine release in the hippocampus. The authors hypothesized that this stimulation enhances long-term potentiation (LTP) in CA1 and depends on the activation of septohippocampal cholinergic neurons. Rats received 105-ng bilateral infusions of 192-IgG-SAP (Cat. #IT-01) into the medial septum. The data suggest that LTP enhancement during vestibular stimulation is mediated by cholinergic septohippocampal cells.

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

Li AJ, Wiater MF, Oostrom MT, Smith BR, Wang Q, Dinh TT, Roberts BL, Jansen HT, Ritter S (2012) Leptin-sensitive neurons in the arcuate nuclei contribute to endogenous feeding rhythms. Am J Physiol Regul Integr Comp Physiol 302(11):R1313-26. doi: 10.1152/ajpregu.00086.2012

Summary: It is clear that the arcuate nucleus (Arc) plays an important role in the generation of feeding rhythms. To clarify how this region modulates signals governing food intake the authors took advantage of the Arc mediation of leptin. Rats received bilateral injections of leptin-SAP (Cat. #IT-47, 56.5 ng per dose) into each Arc. Blank-SAP (Cat. #IT-21) was used as a control. The lesioned animals quickly became obese and displayed arrhythmic eating patterns under normal light conditions. The results indicate that lesioned neurons in the Arc as well as those in the suprachiasmatic nuclei are required for maintenance of feeding rhythms controlled by photic cues.

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

Smith CD, Holschbach MA, Olsewicz J, Lonstein JS (2012) Effects of noradrenergic alpha-2 receptor antagonism or noradrenergic lesions in the ventral bed nucleus of the stria terminalis and medial preoptic area on maternal care in female rats. Psychopharmacology (Berl) 224(2):263-276. doi: 10.1007/s00213-012-2749-2

Summary: The authors investigated the function of norepinephrine in mothering. Lesioned animals received 55-ng infusions of anti-DBH-SAP (Cat. #IT-03) into the ventral bed nucleus of the stria terminalis. Mouse-IgG-SAP (Cat. #IT-18) was used as a control. The results demonstrate that downregulated noradrenergic activity is necessary for postpartum maternal behavior, but is not enough to elicit maternal behavior in nulliparous females.

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

Pedrino GR, Freiria-Oliveira AH, Almeida Colombari DS, Rosa DA, Cravo SL (2012) A2 noradrenergic lesions prevent renal sympathoinhibition induced by hypernatremia in rats. PLoS One 7(5):e37587. doi: 10.1371/journal.pone.0037587

Summary: It is thought that renal sympathetic nerve activity is a key component of the response to acute or chronic elevated concentrations of saline in the blood stream. The authors investigated what neurons are involved in the central control of these responses. Rats received bilateral 6.3 ng injections of anti-DBH-SAP (Cat. #IT-03) into the nucleus of the solitary tract. An equimolar amount (1.3 ng) of saporin (Cat. #PR-01) was used as a control. Loss of the A2 noradrenergic neurons altered the renal sympathetic nerve activity response to elevated saline, suggesting that these neurons help regulate the extracellular fluid compartment.

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

Ma J, Tai SK, Leung LS (2012) Septohippocampal GABAergic neurons mediate the altered behaviors induced by n-methyl-D-aspartate receptor antagonists. Hippocampus 22(12):2208-2218. doi: 10.1002/hipo.22039

Summary: It is thought that the integrity of the medial septum is essential for the maintenance of hippocampal theta rhythm – and that this maintenance depends on three types of septohippocampal neurons; cholinergic, GABAergic, and glutaminergic. In this work the authors administered bilateral injections totaling 140 ng of orexin-SAP (Cat. #IT-20) into the medial septum of rats. The animals were then treated with NMDA receptor antagonists to examine the role of GABAergic neurons from the medial septum in psychotic behavior. The data suggest that septohippocampal GABAergic neurons are important for expression of psychotic symptoms caused by NMDA receptor antagonists.

Related Products: Orexin-B-SAP (Cat. #IT-20)

Lacerda CM, Kisiday J, Johnson B, Orton EC (2012) Local serotonin mediates cyclic strain-induced phenotype transformation, matrix degradation, and glycosaminoglycan synthesis in cultured sheep mitral valves. Am J Physiol Heart Circ Physiol 302(10):H1983-90. doi: 10.1152/ajpheart.00987.2011 PMID: 22345569

Summary: Calcific aortic valve disease and myxomatous mitral valve disease (MMVD) are the most commonly seen degenerative heart valve diseases. Exogenous serotonin has been shown to induce valvulopathy, but current opinion regards serotoninergic and degenerative valvulopathies as unrelated. This work investigated the relationship between serotonin synthesis and strain-induced MMVD in cultured sheep mitral valve leaflets. Anti-SERT (Cat. #AB-N09) was used in immunoblotting experiments. The results demonstrate local serotonin synthesis by mitral valves, modulation of this synthesis by tensile loading, and inhibition of serotonin results in the reduction of strain-mediated protein expression.

Related Products: Antibody to Serotonin Transporter (SERT, Cat. #AB-N09)