Targeting Topics 06q1

Cholinergic septo-hippocampal innervation is required for trace eyeblink classical conditioning.

Fontan-Lozano A, Troncoso J, Munera A, Carrion AM, Delgado-Garcia JM.

Learn Mem 12(6):557-563, 2005.

Classical conditioning of eyeblink responses can be used to evaluate cognitive deficits. The authors lesioned the medial septum/diagonal band of rats with 200 ng of 192-IgG-SAP (Cat. #IT-01), then examined classical and instrumental conditioning paradigms. Lesioned animals displayed a deficit in the acquisition, but not retrieval of eyeblink classical conditioning. The deficit was reversed by carbachol, a cholinergic muscarinic agonist, suggesting a role for the muscarinic system in the acquisition of new motor abilities.

The septohippocampal cholinergic system and spatial working memory in the Morris water maze.

Frielingsdorf H, Thal LJ, Pizzo DP.

Behav Brain Res 168(1):37-46, 2006.

The authors examined whether an optimized Morris water maze test could reveal the role of the septohippocampal cholinergic system in spatial working memory. Rats were treated with bilateral 75-ng injections of 192-IgG-SAP (Cat. #IT-01) followed by acquisition of the water maze task, and two independent phases of working memory testing. Test optimization was followed by icv infusion of nerve growth factor in unlesioned animals. The data demonstrate that working memory impairments cannot be revealed by the Morris water maze test.

Insomnia following hypocretin2-saporin lesions of the substantia nigra.

Gerashchenko D, Blanco-Centurion CA, Miller JD, Shiromani PJ.

Neuroscience 137(1):29-36, 2006.

It is known that orexin (also known as hypocretin) is involved in waking. Here the authors investigate which regions of major arousal areas might be responsible for the changes in sleep-wake architecture upon treatment with orexin-SAP (Cat. #IT-20). Bilateral injection of orexin-SAP into the ventral tegmental (VT) area and the substantia nigra (SN; 92 and 184 ng/μl, 0.25 μl in the VT area and 0.5 μl in the SN) of rats induced insomnia, as well as hyperactivity and stereotypic movements. The results suggest that motor activity is under inhibitory control of the SN.

Selective loss of basal forebrain cholinergic neurons by 192 IgG-saporin is associated with decreased phosphorylation of Ser glycogen synthase kinase-3beta.

Hawkes C, Jhamandas JH, Kar S.

J Neurochem 95(1):263-272, 2005.

Glycogen synthase kinase-3ß (GSK-3ß) is an enzyme involved in a variety of biological events. In this study the authors examined the potential role of GSK-3ß in degeneration of basal forebrain cholinergic neurons. Rats were treated with 2.0 µg per ventricle injections of 192-IgG-SAP (Cat. #IT-01), then GSK-3ß and other cholinergic marker levels were assayed. The results indicate that increased GSK-3ß activity can provide some protection from 192-IgG-SAP-induced degeneration of forebrain cholinergic neurons.

Increased phencyclidine-induced hyperactivity following cortical cholinergic denervation.

Mattsson A, Lindqvist E, Ogren SO, Olson L.

Neuroreport 16(16):1815-1819, 2005.

A potential contribution to schizophrenia is altered cholinergic function. The authors investigated how lesioning cholinergic corticopetal projections might affect glutaminergic activity. Rats were injected with 0.134 µg of 192-IgG-SAP (Cat. #IT-01) into the nucleus basalis magnocellularis. The authors found that cholinergic lesioning of the neocortex led to enhanced sensitivity to phencyclidine, which has been shown to induce clinical symptoms similar to those of schizophrenia. These data suggest that glutaminergic dysfunction may be relevant to schizophrenia pathophysiology.

Sleep-disordered breathing after targeted ablation of preBotzinger complex neurons.

McKay LC, Janczewski WA, Feldman JL.

Nat Neurosci 8(9):1142-1144, 2005.

Sleep-disordered breathing is common in elderly humans as well as patients with neurodegenerative disease. The authors investigated the role of preBötzinger complex neurons of rats in respiratory rhythm generation. Using the fact that preBötzinger complex neurons in the ventrolateral medulla express the neurokinin-1 receptor, animals were given bilateral injections of SP-SAP (Cat. #IT-07). Beginning 7 days post-injection, lesioned animals displayed marked respiratory disturbances during both sleep and wakeful periods.

Estrogen contributes to structural recovery after a lesion.

Saenz C, Dominguez R, de Lacalle S.

Neurosci Lett 392(3):198-201, 2006.

The authors evaluated the trophic effects of 17ß-estradiol (E2) on cholinergic neurons of the basal forebrain after lesioning with 192-IgG-SAP (Cat. #IT-01). Ovariectomized female rats received 200 nl of 0.075 mg/ml 192-IgG-SAP followed by a subcutaneous pellet of E2, which was released over 60 days. Dendritic size in ovariectomized rats receiving the E2 was the same as in control animals, while ovariectomized rats receiving a placebo displayed a significant reduction in dendritic arborization.

Selective acetylcholine and dopamine lesions in neonatal rats produce distinct patterns of cortical dendritic atrophy in adulthood.

Sherren N, Pappas BA.

Neuroscience 136(2):445-456, 2005.

In this work the authors examined lesions of acetylcholine afferents in 7-day-old rat pups, and the effect on dendritic development. 600 ng of 192-IgG-SAP (Cat. #IT-01) were administered to the ventricles of test animals. Various morphological changes in the retrosplenial cortex were observed, including smaller apical tufts and fewer basilar dendritic branches in layer V medial prefrontal cells. The data demonstrate that ascending acetylcholine afferents are very important in the development of cortical cytoarchitecture.

Saporin and ricin A chain follow different intracellular routes to enter the cytosol of intoxicated cells.

Vago R, Marsden CJ, Lord JM, Ippoliti R, Flavell DJ, Flavell SU, Ceriotti A, Fabbrini MS.

FEBS J 272(19):4983-4995, 2005.

Some bacterial toxins such as Pseudomonas aeruginosa exotoxin A carry a KDEL-like C-terminal peptide sequence, which targets the protein to the endoplasmic reticulum. Saporin (Cat. #PR-01) is a plant ribosome-inactivating protein, which does not contain a KDEL-like sequence. Here the authors examined the intracellular pathways utilized by saporin. Although ricin, another plant ribosome-inactivating protein, could be visualized in the Golgi complex, saporin was not. The data suggest that saporin may utilize endosomes during its journey through the cell.

Nicotine-induced switch in the nicotinic cholinergic mechanisms of facilitation of long-term potentiation induction.

Yamazaki Y, Jia Y, Hamaue N, Sumikawa K.

Eur J Neurosci 22(4):845-860, 2005.

The authors investigated cellular mechanisms underlying improved cognitive function in Alzheimer’s disease patients upon the administration of nicotine. To model Alzheimer’s disease in rats, 2 µg of 192-IgG-SAP (Cat. #IT-01) was injected into the lateral cerebral ventricle. Examination of the lesioned animals suggests that nicotine promotes the induction of long-term potentiation by enhancing N-methyl-D-aspartate responses, and suppressing acetylcholine-mediated mechanisms in pyramidal cells.