Targeting Topics 03q2

Effects of lateral hypothalamic lesion with the neurotoxin hypocretin-2-saporin on sleep in Long-Evans rats.

Gerashchenko D, Blanco-Centurion C, Greco MA, Shiromani PJ.

Neuroscience 116(1):223-235, 2003.

Recent data has linked narcolepsy to the loss of neurons containing the neuropeptide hypocretin, also known as orexin. The authors wished to investigate whether the variance in severity of narcolepsy could be explained by the extent of loss of these neurons. After injection of 90 or 490 ng of orexin-SAP (Cat. #IT-20) into the lateral hypothalamus, the measurement of several parameters demonstrated the severity of narcolepsy may be linked to the degree of loss of neurons expressing the orexin receptor.

Ablation of NK1 receptors in rat nucleus tractus solitarii blocks baroreflexes.

Riley J, Lin LH, Chianca DAJ, Talman WT.

Hypertension 40(6):823-826, 2002.

Stimulation of arterial baroreflexes releases the neuropeptide substance P (SP) from vagal afferent nerves within the nucleus tractus solitarii. To ascertain whether the neurons taking up this SP are critical to baroreflex transmission, the authors injected 18 ng SP-SAP (Cat. #IT-07) into the nucleus tractus solitarii of rats. In animals that received bilateral injections, baroreflex gain was significantly reduced, indicating that neurons expressing SP receptors play a critical role in mediation of this process.

Effects of lesions of basal forebrain cholinergic neurons in newborn rats on susceptibility to seizures.

Silveira DC, Cha BH, Holmes GL.

Brain Res Dev Brain Res 139(2):277-283, 2002.

It has previously been shown that adult rats treated with the cholinergic lesioning agent 192-Saporin (Cat. #IT-01) display increased susceptibility to generalized seizures. Here, the authors studied the effects of 200 ng intracerebroventricular injections of 192- Saporin in neonatal rats. Although treated rats did not demonstrate differences in seizure duration or EEG ictal duration, a significantly shorter latency to seizure onset was observed. No significant differences were observed in spatial learning between treated and control rats.

Immunolesion of norepinephrine and epinephrine afferents to medial hypothalamus alters basal and 2-deoxy-D-glucose-induced neuropeptide Y and agouti gene-related protein messenger ribonucleic acid expression in the arcuate nucleus.

Fraley GS, Ritter S.

Endocrinology 144(1):75-83, 2003.

Neuropeptide Y (NPY) and agouti gene-related protein (AGRP) are important peptides in the control of food intake. Prior studies have shown that mRNAs for both these peptides are increased in the arcuate nucleus of the hypothalamus (ARC) by glucoprivation. Using bilateral 42 ng intracranial injections of anti- DBH-SAP (Cat. #IT-03) in rats, the authors investigated the role of hindbrain catecholamine afferents in this increased ARC NPY and AGRP gene expression. The results indicate that these afferents contribute to basal NPY and AGRP gene expression as well as mediate the responsiveness of NPY and AGRP neurons to glucose deprivation.

Specific contributions of the basal forebrain corticopetal cholinergic system to electroencephalographic activity and sleep/waking behaviour.

Berntson GG, Shafi R, Sarter M.

Eur J Neurosci 16(12):2453-2461, 2002.

There is a large amount of data suggesting the basal forebrain cholinergic system plays an important part in arousal and REM sleep. In this study the authors used 192-Saporin (Cat. #IT-01, 0.05 μg injected into the basal forebrain of each hemisphere) to lesion the corticopetal projection and examined cortical EEG activity across sleep/wake states. Lesioned animals displayed significantly reduced high frequency EEG activity across all stages of sleeping and wakefulness, indicating that the basal forebrain cholinergic system may exert a general activational effect on the cortical mantle.

Neurotransmitter release and its presynaptic modulation in the rat hippocampus after selective damage to cholinergic or/and serotonergic afferents.

Birthelmer A, Ehret A, Amtage F, Forster S, Lehmann O, Jeltsch H, Cassel JC, Jackisch R.

Brain Res Bull 59(5):371-381, 2003.

Previous studies have investigated some of the modulatory mechanisms present in the denervated hippocampus. These studies have used nonselective denervation models, therefore it is difficult to assign results to the lesion of any specific system. This study examined the interaction of lesions caused by 192-Saporin (Cat. #IT-01,
0.4 μg injected into the medial septum/diagonal band of broca) and 5,7-DHT. The authors were able to establish controlled and selective damage to more than one transmitter system, allowing examination of the interaction between multiple-lesioned systems.

A group of glutamatergic interneurons expressing high levels of both neurokinin-1 receptors and somatostatin identifies the region of the pre-Botzinger complex.

Stornetta RL, Rosin DL, Wang H, Sevigny CP, Weston MC, Guyenet PG.

J Comp Neurol 455(4):499-512, 2003.

Study of the pre-Bötzinger complex (pre-BötC) has been hindered by the lack of a specific marker. Using SSP-SAP (Cat. #IT-11, three 0.313-ng unilateral injections in the rostral part of the ventral respiratory group) coupled with in situ hybridization and the labeling of selected markers, the authors examined whether somatostatin (SST) might be a marker for this region. The data suggest that a subgroup of cells containing high levels of SST and neurokinin-1 receptor immunoreactivity may identify the pre- BötC.

Effects of septal cholinergic lesion on rat exploratory behavior in an open-field.

Lamprea MR, Cardenas FP, Silveira R, Walsh TJ, Morato S.

Braz J Med Biol Res 36(2):233-238, 2003.

Exploratory behavior triggered by novelty involves the medial septum. The authors lesioned the medial septum in rats with 237.5-ng injections of 192- Saporin (Cat. #IT-01) and examined the behavior of these animals in a model for novelty. The results suggest not only do septohippocampal cholinergic mechanisms contribute to the motivation to explore new environments, they also are related to the acquisition and storage of spatial information.

Selective joint denervation promotes knee osteoarthritis in the aging rat.

Salo PT, Hogervorst T, Seerattan RA, Rucker D, Bray RC.

J Orthop Res 20(6):1256-1264, 2002.

Noting that mice lose joint afferents with aging, and that this loss precedes osteoarthritis development, the authors investigated the effects of denervating the knee joints of young rats. Injection of 10 μl OX7-SAP (Cat. #IT-02) into the knee joint space produced severe degenerative cartilage changes as well as a significant reduction in the number of joint afferents. These changes indicate that joint denervation predisposes a joint to osteoarthritic changes more severe than those found with aging alone.

Neurobiology of substance P and the NK1 receptor.

Mantyh PW.

J Clin Psychiatry 63 Suppl 11:6-10, 2002.

The NK-1 receptor system is somewhat unusual in that it is expressed on only 5- 7% of neurons in the central nervous system. Dr. Patrick Mantyh reviews how tools such as SP-SAP (Cat. #IT-07) have been used to begin defining the roles of substance P and the NK-1 receptor in affective behavior.