Targeting Topics 05q1

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.

The authors examined the effect of 48 ng injections of NPY-SAP (Cat. #IT-28) into the basomedial hypothalamus (BMH) on glucoprivic feeding in rats. While there was no evidence of retrograde transport, the lesions inhibited responses to intracerebroventricular leptin and ghrelin. Neither the feeding nor the hyperglycemic response to 2-deoxy-D-glucose was affected by the lesion, indicating that these hindbrain processes do not utilize neurons in the BMH. This work also describes dosing and injection parameter studies for the use of NPY-SAP.

Medullary noradrenergic neurons release norepinephrine in the medial amygdala in females in response to mating stimulation sufficient for pseudopregnancy.

Cameron NM, Carey P, Erskine MS.

Brain Res 1022(1-2):137-147, 2004.

Norepinephrine (NE) plays an important role in female reproductive function. While the ventral noradrenergic bundle is known to be necessary for transmitting the pseudopregnancy (PSP) response, the mechanism by which this occurs is not understood. The authors administered 20 ng of Anti-DBH-SAP (Cat. #IT-03) to the left posterodorsal medial amygdala of ovariectomized rats. The results indicate that NE may play an important role in the establishment of PSP.

Involvement of brainstem catecholaminergic inputs to the hypothalamic paraventricular nucleus in estrogen receptor alpha expression in this nucleus during different stress conditions in female rats.

Estacio MA, Tsukamura H, Reyes BA, Uenoyama Y, I’anson H, Maeda K.

Endocrinology 145(11):4917-4926, 2004.

Norepinephrine release in the paraventricular nucleus (PVN) is increased during periods of metabolic stress. The authors hypothesized that noradrenergic inputs to the PVN may also mediate estrogen receptor a (ERa) expression in the PVN during metabolic stress. 20 ng of Anti-DBH-SAP (Cat. #IT-03) was injected bilaterally into the PVN of rats, and ERa expression was examined in several stress models. Results indicate that during metabolic stress catecholaminergic inputs to the PVN play a major role in mediating the induction of ERa expression.

Exogenous testosterone prevents motoneuron atrophy induced by contralateral motoneuron depletion.

Fargo KN, Sengelaub DR.

J Neurobiol 60(3):348-359, 2004.

Gonadal steroids have been shown to supply a variety of neuroprotective and neurotherapeutic effects. Using 1-µl injections of 0.1% CTB-SAP (Cat. #IT-14) into the ipsalateral bulbocavernosus and the levator ani of rats, the authors examined the protective effects of testosterone on motoneuron morphology. After the lesion was induced some rats were castrated, and all animals were treated with exogenous testosterone. The results suggest that high-normal levels of testosterone can prevent motoneuron atrophy induced by contralateral motoneuron depletion.

Transient attenuation of CO2 sensitivity after neurotoxic lesions in the medullary raphe area of awake goats.

Hodges MR, Opansky C, Qian B, Davis S, Bonis J, Bastasic J, Leekley T, Pan LG, Forster HV.

J Appl Physiol 97(6):2236-2247, 2004.

The authors wished to investigate the influence medullary raphe-area neurons have on breathing. This control may be through CO2/H+ chemoreceptors and/or through non-chemoreceptor modulation. 1 or 10 µl of 50 pM SP-SAP (Cat. #IT-07) or Saporin (Cat. #PR-01) was injected into the raphe of goats. Breathing and CO2 sensitivity were evaluated during different physiologic conditions. The data suggest that SP receptor- and glutamate receptor-expressing neurons in the medullary raphe both influence CO2 sensitivity, but not altered breathing periods.

No facilitation of amphetamine- or cocaine-induced hyperactivity in adult rats after various 192 IgG-saporin lesions in the basal forebrain.

Jeltsch H, Lazarus C, Cosquer B, Galani R, Cassel JC.

Brain Res 1029(2):259-271, 2004.

Previous data have indicated that intracerebroventricular (icv) injections of 192-Saporin (Cat. #IT-01) induce a dramatic increase of the locomotor response to amphetamine. The authors of this study examined the locomotor effects of several lesions on the response to amphetamine or cocaine. Rats were injected with 5 µg 192-Saporin icv or 0.4 µg bilaterally into the septal region, or 0.4 µg into the nucleus basalis magnocellularis. While the results did not confirm the amphetamine effect, they did suggest that the effect of cocaine can be altered by these lesions.

Spinal neurons that express NK-1 receptors modulate descending controls that project through the dorsolateral funiculus.

Khasabov SG, Ghilardi JR, Mantyh PW, Simone DA.

J Neurophysiol 93(2):998-1006, 2005.

The involvement of neurokinin-1 receptor-expressing neurons in the spinal cord with the ascending systems of hyperalgesia and central sensitization has been well established. The authors used 10 µl injections of 5 µM SP-SAP (Cat. #IT-07) into the intrathecal space of rats, and examined the descending systems that travel via the dorsolateral funiculus (DLF). While SP-SAP alone had no effect, administration of SP-SAP in conjunction with a DLF transection enhanced neuronal responses to mechanical and heat stimuli.

The medial septum mediates impairment of prepulse inhibition of acoustic startle induced by a hippocampal seizure or phencyclidine.

Ma J, Shen B, Rajakumar N, Leung LS.

Behav Brain Res 155(1):153-166, 2004.

Deficits in sensorimotor gating, suppression of a motor response by a sensory stimulus are found in schizophrenic patients, as well as laboratory animals after administration of compounds such as phencyclidine (PCP). The authors lesioned the cholinergic system of the medial septum in rats with 0.14-0.21 µg injections of 192-Saporin (Cat. #IT-01) to examine the involvement of these neurons in sensorimotor gating. The authors suggest that GABAergic, but not cholinergic septohippocampal neurons mediate this deficit.

The behavioral and neuroanatomical effects of IB4-saporin treatment in rat models of nociceptive and neuropathic pain.

Tarpley JW, Kohler MG, Martin WJ.

Brain Res 1029(1):65-76, 2004.

Using the fact that primary afferent neurons bind isolectin B4 (IB4), the authors injected 5 µg of IB4-SAP (Cat. #IT-10) into the sciatic nerve in the left thigh. After recovery, these animals were then treated with a L5 spinal nerve ligation. Lesioned animals displayed attenuated NGF-induced hyperalgesia, as well as differences in other pain-model markers. The data indicate that IB4-positive C-fibers play a discrete role in NGF-induced hyperalgesia, as well as in the development of neuropathic pain.

Small reduction of neurokinin-1 receptor-expressing neurons in the pre-Botzinger complex area induces abnormal breathing periods in awake goats.

Wenninger JM, Pan LG, Klum L, Leekley T, Bastastic J, Hodges MR, Feroah T, Davis S, Forster HV.

J Appl Physiol 97(5):1620-1628, 2004.

Previous work has shown that lesion of the pre-Bötzinger Complex (pre-BötzC) of rats with SP-SAP (Cat. #IT-07) results in hypoventilation and an abnormal breathing pattern. The authors used 1 or 10 µl of 50 pM SP-SAP bilaterally injected into the pre-BötzC area to further investigate this system in goats. The results show transient changes in respiratory rhythm and respiratory muscle activation patterns, indicating that SP receptor-expressing neurons in the pre-BötzC are involved in the regulation of respiration.

Large lesions in the pre-Botzinger complex area eliminate eupneic respiratory rhythm in awake goats.

Wenninger JM, Pan LG, Klum L, Leekley T, Bastastic J, Hodges MR, Feroah TR, Davis S, Forster HV.

J Appl Physiol 97(5):1629-1636, 2004.

Previously the authors demonstrated that lesioning the pre-Bötzinger Complex (pre-BötzC) with SP-SAP (Cat. #IT-07) resulted in transient disruptions of normal respiratory muscle activation in goats. The purpose of this study was to examine the effects of a more complete lesion of the pre-BötzC area. The authors treated SP-SAP-lesioned goats with ibotenic acid. The results suggest that the pre-BötzC is critical for generating a normal respiratory rhythm during the awake state.