Targeting Topics 08q2

Septal grafts restore cognitive abilities and amyloid precursor protein metabolism.

Aztiria E, Cataudella T, Spampinato S, Leanza G.

Neurobiol Aging 30(10):1614-1625, 2009.

Although cholinergic loss and the presence of b-amyloid plaques are well documented in Alzheimer’s disease, it is unknown whether restoration of regulatory cholinergic inputs affects in vivo b-amyloid precursor protein (APP). 5 µg of 192-IgG-SAP (Cat. #IT-01) was split between the lateral ventricles of rats. 6 months post-surgery the animals were implanted with cholinergic-rich septal tissue grafts. Grafted animals exhibited normal or near-normal levels of APP. APP levels, as well as improved spatial navigation performance, correlated strongly with graft-induced cholinergic changes.

Reactive oxygen species generation by the ethylene-bis-dithiocarbamate (EBDC) fungicide mancozeb and its contribution to neuronal toxicity in mesencephalic cells.

Domico LM, Cooper KR, Bernard LP, Zeevalk GD.

Neurotoxicology 28(6):1079-1091, 2007.

This work explores the mechanisms of neuronal damage associated with the ethylene-bis-dithiocarbamate fungicide mancozeb (MZ). In order to obtain a purified rat mesencephalic culture, the authors treated neuronal cultures with Mac-1-SAP (Cat. #IT-33) at a final concentration of 2 µg/ml. The microglia-free cultures did not display attenuated reactive oxygen species (ROS) production when treated with MZ. The data suggest that microglia are not required for ROS production in the presence of MZ.

Basal forebrain and saporin cholinergic lesions: the devil dwells in delivery details.

Kalinchuk AV, Porkka-Heiskanen T, McCarley RW.

Sleep 29(11):1385-7; discussion 1387-9, 2006.

The authors of this commentary discuss results presented by Blanco-Centurion et. al. (J Neurosci 26: 8092-8100, 2006). The topic is the role of adenosine in the basal forebrain in the control of sleep homeostasis. Discussion covers the potential differences found when 192-IgG-SAP (Cat. #IT-01) is administered locally as compared to an intracerebroventricular injection.

Effects of ibotenate and 192IgG-saporin lesions of the nucleus basalis magnocellularis/substantia innominata on spontaneous sleep and wake states and on recovery sleep after sleep deprivation in rats.

Kaur S, Junek A, Black MA, Semba K.

J Neurosci 28(2):491-504, 2008.

The caudal basal forebrain of rats was lesioned with 0.26-µg bilateral injections of 192-IgG-SAP (Cat. #IT-01) in order to examine the role of this area of the brain in several facets of sleep behavior. The results suggest that cholinergic neurons and non-cholinergic neurons in the basal forebrain play different, but important roles in non-rapid eye movement sleep and EEG delta power after sleep loss. Non-cholinergic basal forebrain neurons inhibit delta waves, whereas cholinergic neurons promote wake.

Elimination of rat spinal substance P receptor bearing neurons dissociates cardiovascular and nocifensive responses to nicotinic agonists.

Khan IM, Wart CV, Singletary EA, Stanislaus S, Deerinck T, Yaksh TL, Printz MP.

Neuropharmacology 54(2):269-279, 2008.

Nocifensive behavior and cardiovascular responses due to nicotinic agonists may be sustained by substance P positive primary afferents. Rats received 10 µl intrathecal injections of 10 µM SP-SAP (Cat. #IT-07), unconjugated saporin (Cat. #PR-01) was used as a control. Lesioned animals displayed reduced nocifensive response to nicotinic agonists, but cardiovascular responses were not changed. Tachycardia and pressor responses were enhanced upon administration of cytisine and epibatidine.

Spinal mu-opioid receptor-expressing dorsal horn neurons: role in nociception and morphine antinociception.

Kline RHt, Wiley RG.

J Neurosci 28(4):904-913, 2008.

The authors used Dermorphin-SAP (Cat. #IT-12) to investigate the function of spinal cord mu-opioid receptor (MOR)-expressing dorsal horn neurons in nociception and morphine analgesia. Rats were treated with 500 ng intrathecal injections of Dermorphin-SAP; 500 ng of Blank-SAP (Cat. #IT-21), and up to 1 µg of Saporin (Cat. #PR-01) were used as controls. The data indicate that MOR-expressing dorsal horn neurons are necessary for morphine action and play a role in nocifensive responses to persistent pain in the formalin test.

Brainstem catecholaminergic neurons modulate both respiratory and cardiovascular function.

Li A, Emond L, Nattie E.

Adv Exp Med Biol 605:371-376, 2008.

The authors examined the role of brainstem catecholamine (CA) neurons in various aspects of breathing and chemoreception. Rats received 5-µg injections of anti-DBH-SAP (Cat. #IT-03) into the 4th ventricle; mouse IgG-SAP (Cat. #IT-18) was used as a control. This method of lesioning left the CA neurons in the peripheral nervous system intact. Lesioned animals displayed a constant decrease in breathing frequency, reduced response to CO2, and increased variability of breathing during REM sleep. Inhibitory cardiovascular effects were also seen.

Neuroanatomical and behavioral effects of a novel version of the cholinergic immunotoxin mu p75-saporin in mice.

Moreau PH, Cosquer B, Jeltsch H, Cassel JC, Mathis C.

Hippocampus 18(6):610-622, 2008.

192-IgG-SAP (Cat. #IT-01) has been used for over a decade to examine the cholinergic system in the basal forebrain of rats. Establishing the same reagent for mice has been problematic. Here the authors describe the use of a mouse-specific lesioning agent, mu p75-SAP (Cat. #IT-16). After deciding on a dosage of 0.4 µg administered in the form of bilateral intracerebroventricular injections, mice were lesioned and tested. Lesioned animals displayed increased locomotor activity, and spatial learning and memory deficits, with minimal side effects.

Cholinergic Deafferentation of Prefrontal Cortex Increases Sensitivity to Cross-Modal Distractors during a Sustained Attention Task.

Newman LA, McGaughy J.

J Neurosci 28(10):2642-2650, 2008.

The authors injected 5 ng of 192-IgG-SAP (Cat. #IT-01) into the prefrontal cortex of rats to investigate the effect of cholinergic loss on distractors to attentional demand. Where all animals experienced impaired performance in the presence of visual distractions, lesioned animals were more sensitive to auditory distractions. While these results indicate compromised top-down processing, lesioned animals also showed improved performance in bottom-up processing – possibly caused by a shift in circuit dynamics after the lesion.

Selective impairment of the cerebellar C1 module involved in rat hind limb control reduces step-dependent modulation of cutaneous reflexes.

Pijpers A, Winkelman BH, Bronsing R, Ruigrok TJ.

J Neurosci 28(9):2179-2189, 2008.

The cerebellar cortex is arranged in a series of modules. Elucidation of module-specific function has been difficult because of the closely arranged structure of these modules. Here the authors lesioned the C1/C3 hindlimb module of the rat with CTB-SAP (Cat. #IT-14). Rats received 75-125 ng injections of CTB-SAP into the C1 zone of the copula pyramidis or the paramedian lobule of the right cerebellar hemisphere. C1-injected animals displayed marked diminishment of cutaneously induced reflexes with no significant impact on walking or stepping pattern.

The pedunculopontine tegmental nucleus and the nucleus basalis magnocellularis: do both have a role in sustained attention?

Rostron CL, Farquhar MJ, Latimer MP, Winn P.

BMC Neurosci 9:16, 2008.

This study provided further investigation into the role of the pedunculopontine tegmental nucleus (PPTg) in control of sustained attention. Rats were given 0.13 µg injections of 192-IgG-SAP (Cat. #IT-01) into the nucleus basalis magnocellularis. The immunotoxin-treated animals were compared to animals receiving ibotenate injections into the PPTg. Results suggest that ibotenate lesions cause impaired selection of conditioned response as shown by an increase in unconditioned behaviors. 192-IgG-SAP treated animals exhibited difficulty obtaining successful lever presses linked to attention.