Targeting Topics 05q2

Basomedial hypothalamic injections of neuropeptide Y conjugated to saporin selectively disrupt hypothalamic controls of food intake.

Bugarith K, Dinh TT, Li AJ, Speth RC, Ritter S.

Endocrinology 146(3):1179-1191, 2005.

Neurons in the arcuate nucleus (ARC) that coexpress neuropeptide-Y (NPY) and Agouti gene-related protein may be involved in glucoprivic feeding. The authors investigated the use of NPY-SAP (Cat. #IT-28) to eliminate neurons expressing NPY receptors. Bilateral injections of 48 ng of NPY-SAP were made into the basomedial hypothalamus dorsal to the ARC in rats. While the NPY-SAP lesions impaired responses to leptin and ghrelin, the data do not support the role of NPY/AGRP neurons as mediators of glucoprivic feeding.

Impairment of skilled forelimb use after ablation of striatal interneurons expressing substance P receptors in rats: an analysis using a pasta matrix reaching task.

Chiken S, Tokuno H.

Exp Brain Res 162(4):532-536, 2005.

The substance P receptor is expressed by two types of interneurons in the striatum. The authors investigated whether elimination of these neurons would impair motor control by the basal ganglia. Rats were treated with 7.5 ng injections of SP-SAP (Cat. #IT-07) into the dorsolateral part of the striatum. Lesioned animals did not perform as well as controls in a test measuring accurate reaching with the forepaw. The data show that striatal interneurons expressing the substance P receptor are necessary for accurate reaching.

Effects of lesions of the histaminergic tuberomammillary nucleus on spontaneous sleep in rats.

Gerashchenko D, Chou TC, Blanco-Centurion CA, Saper CB, Shiromani PJ.

Sleep 27(7):1275-1281, 2004.

Although evidence suggests that histaminergic neurons in the tuberomammillary nucleus (TMN) promote wakefulness, this has not been investigated using specific lesioning agents. In this study, the authors utilize the fact that TMN neurons express the orexin-B receptor by eliminating these neurons with an injection of 50 ng of orexin-SAP (Cat. #IT-20) into the posterior hypothalamus. The data indicate that histaminergic neurons are not required for the homeostatic regulation of sleep.

The effect of central cholinergic and noradrenergic denervation on hippocampal sympathetic ingrowth and apoptosis-like reactivity in the rat.

Harrell LE, Parsons DS, Kolasa K.

Brain Res 1033(1):68-77, 2005.

Cholinergic denervation of the hippocampus is followed by ingrowth of peripheral sympathetic fibers originating from the superior cervical ganglion. The authors injected 1 µg of 192-Saporin (Cat. #IT-01) into the medial septum of rats along with a noradrenergic fiber neurotoxin to investigate whether the noradrenergic system was involved with this ingrowth as well. The data provide more evidence that hippocampal sympathetic ingrowth can be stimulated by cholinergic denervation alone.

Sexually dimorphic effects of hippocampal cholinergic deafferentation in rats.

Jonasson Z, Cahill JF, Tobey RE, Baxter MG.

Eur J Neurosci 20(11):3041-3053, 2004.

Studies of cholinergic neuron lesions have been performed almost exclusively in male animals. In this work, the authors examined the differences of cholinergic lesions between males and females. Rats were treated with four injections totaling 0.15 µg of 192-Saporin (Cat. #IT-01) into the medial septum/vertical limb of the diagonal band. The results demonstrate differences in learning and memory processes between male and female rats.

Aging and cholinergic deafferentation alter GluR1 expression in rat frontal cortex.

Kim I, Wilson RE, Wellman CL.

Neurobiol Aging 26(7):1073-1081, 2005.

Neuronal plasticity is involved in several processes during adulthood, including learning and memory, and recovery from injury. Recent evidence suggests that aging reduces this plasticity. The authors used 0.15 µg injections of 192-Saporin (Cat. #IT-01) into the nucleus basalis magnocellularis of rats to investigate how the loss of cortical plasticity would affect the expression of GluR1. Younger animals displayed a marked increase in the number of GluR1-expressing neurons, a compensatory response not seen in older animals.

Hebb-Williams performance and scopolamine challenge in rats with partial immunotoxic hippocampal cholinergic deafferentation.

Marques Pereira P, Cosquer B, Schimchowitsch S, Cassel JC.

Brain Res Bull 64(5):381-394, 2005.

Much of the recent work done on the role of cholinergic neurons in the hippocampus has been focused on detecting subtle learning deficits. In this study, the authors investigated the effect of 0.368 µg of 192-Saporin (Cat. #IT-01) administered to the medial septum of rats in four injections. A complex learning task, the Hebb-Williams maze, was used to define small deficits in the learning performance of the lesioned animals prior to, and after the injection of scopolamine.

Forebrain acetylcholine regulates adult hippocampal neurogenesis and learning.

Mohapel P, Leanza G, Kokaia M, Lindvall O.

Neurobiol Aging 26(6):939-946, 2005.

New hippocampal neurons that are thought to be involved in memory formation are generated in the dentate gyrus (DG) throughout adulthood. In this study, rats were injected at various sites with 192-Saporin (Cat. #IT-01). The authors found that acetylcholine levels, which are reduced upon administration of 192-Saporin, are linked to proliferation and/or short-term survival of DG neurons, rather than long-term survival or differentiation. Cognitive defects that could be linked to the reduced number of new neurons were also observed.

Purkinje cell loss by OX7-saporin impairs excitatory and inhibitory eyeblink conditioning.

Nolan BC, Freeman JHJ.

Behav Neurosci 119(1):190-201, 2005.

Although the contributions of the cortical cerebellum to eyeblink-conditioned excitation have been extensively investigated, involvement in inhibition of this reflex is unclear. After intracerebroventricular infusions of 15.0 µg of OX7-SAP (Cat. #IT-02), rats displayed impaired retention and savings of preinfusion excitatory conditioning, indicating that the Purkinje cells that were eliminated by OX7-SAP are essential for maintenance of excitatory eyeblink conditioning. Inhibition is not prevented by loss of these Purkinje cells, suggesting that extracerebellar structures play a critical role in this process.

Elimination of rat spinal neurons expressing neurokinin 1 receptors reduces bladder overactivity and spinal c-fos expression induced by bladder irritation.

Seki S, Erickson KA, Seki M, Nishizawa O, Igawa Y, Ogawa T, de Groat WC, Chancellor MB, Yoshimura N.

Am J Physiol Renal Physiol 288(3):F466-73, 2005.

Substance P is reported to play a role in the micturition reflex as well as in nociceptive responses. The authors investigated the role that neurokinin-1 receptor-expressing cells in the spinal cord play in the micturition reflex of rats. 8 µl of 1.0 or 1.5 µM SSP-SAP (Cat. #IT-11) was injected into the L6-S1 level of the spinal cord, and cystometric parameters were measured before and after capsaicin administration to the bladder. Lesioned animals did not display the bladder overactivity normally seen in the presence of capsaicin.

Involvement of GABAergic and cholinergic medial septal neurons in hippocampal theta rhythm.

Yoder RM, Pang KC.

Hippocampus 15(3):381-392, 2005.

It is thought that hippocampal theta rhythm (HPCθ) is involved in attention and acquisition of sensory information. The HPCθ circuit includes the medial septum/diagonal band of Broca (MSDB), which projects to the hippocampus through GABAergic and cholinergic neurons. A total of 0.325 µg of 192-Saporin (Cat. #IT-01) was injected into the MSDB of rats. Hippocampal recordings measuring field potential oscillations were taken, indicating that both GABAergic and cholinergic neurons are involved in HPCθ.