Targeting Topics 04q2

Extrinsic regulation of injury/growth-related gene expression in the inferior olive of the adult rat.

Buffo A, Carulli D, Rossi F, Strata P.

Eur J Neurosci 18(8):2146-2158, 2003.

Inferior olive (IO) cells of the CNS have the ability to regenerate axons after injury, even when the injury is close to the terminal field. After administration of 2.2 µg of 192-Saporin (Cat. #IT-01) and a control immunotoxin (mouse IgG-SAP, Cat #IT-18) to each ventricle in rats, two subsets of IO cells were discovered. Each subset responded differently to injury indicating that multiple mechanisms are responsible for their intrinsic regenerative potential.

Cholinergic modulation of visual attention and working memory: dissociable effects of basal forebrain 192-IgG-saporin lesions and intraprefrontal infusions of scopolamine.

Chudasama Y, Dalley JW, Nathwani F, Bouger P, Robbins TW.

Learn Mem 11(1):78-86, 2004.

It is hypothesized that cortical cholinergic dysfunction underlies the cognitive impairments associated with dementia and normal aging. The authors examined the role of these neurons in both attentional and mnemonic functions, using either bilateral infusions of 125 ng of 192-Saporin (Cat. #IT-01) into the bregma of rats or infusions of scopolamine. The results suggest that attentional and working memory capacities can be tested separately during the same session. It is also indicated that the CBF system is a modulator of both attentional and mnemonic processing.

Testosterone manipulation protects motoneurons from dendritic atrophy after contralateral motoneuron depletion.

Fargo KN, Sengelaub DR.

J Comp Neurol 469(1):96-106, 2004.

The authors wished to investigate the therapeutic effects of testosterone on motoneuron dendrites in nerve injury models. 1 µl of a 0.1% solution of CTB-SAP (Cat. #IT-14) solution was unilaterally injected into the ispilateral bulbocavernosus and levator ani muscles of rats, and the contralateral motoneuron morphology was examined. In castrated rats receiving testosterone, dendrites in the spinal nucleus of the bulbocavernosus grew after CTB-SAP treatment. This is a demonstration of the neuroprotective/neurotherapeutic role of testosterone in the nervous system.

Effects of complete immunotoxin lesions of the cholinergic basal forebrain on fear conditioning and spatial learning.

Frick KM, Kim JJ, Baxter MG.

Hippocampus 14(2):244-254, 2004.

The authors examined the hypothesis that basal forebrain cholinergic neurons are critical for acquisition and consolidation of fear conditioning by lesioning the medial septum/vertical limb of the diagonal band, the horizontal limb of the diagonal band of Broca, and the nucleus basalis magnocellularis of rats with 192-Saporin (Cat. #IT-01). The lesions did not impair contextual fear conditioning, implying that impairments induced by scopolamine may not be mediated by cholinergic input to the hippocampus and neocortex.

Relationship between CSF hypocretin levels and hypocretin neuronal loss.

Gerashchenko D, Murillo-Rodriguez E, Lin L, Xu M, Hallett L, Nishino S, Mignot E, Shiromani PJ.

Exp Neurol 184(2):1010-1016, 2003.

Narcolepsy has recently been shown to be a neurodegenerative disease. Data from several different sources indicate that narcoleptics have very low levels of hypocretin (HCRT)-containing neurons. The authors sought to verify a direct linkage between HCRT-containing neurons and HCRT levels in the CSF. Rats were lesioned with 45-90 ng of orexin-SAP (Cat. #IT-20) bilaterally into the lateral hypothalamus. Loss of HCRT neurons correlated with decreased levels of HCRT in the CSF.

Transfer effects and conditional learning in rats with selective lesions of medial septal/diagonal band cholinergic neurons.

Janisiewicz AM, Baxter MG.

Behav Neurosci 117(6):1342-1352, 2003.

Conditional learning appears to require cholinergic input to the hippocampus and cingulate cortex. Using a total of 0.5 µl of 0.12 µg/µl 192-Saporin (Cat. #IT-01) injected into the medial septal area of rats, the authors investigated the role of cholinergic input in conditional learning. The results suggest that cholinergic neurons of the medial septum/vertical limb of the diagonal band play a role in the transfer of behavioral experience rather than in conditional learning itself.

Environment-spatial conditional learning in rats with selective lesions of medial septal cholinergic neurons.

Janisiewicz AM, Jackson Or, Firoz EF, Baxter MG.

Hippocampus 14(2):265-273, 2004.

192-Saporin (Cat. #IT-01) has produced varied results when used to determine the role of cholinergic neurons of the medial septum/vertical limb of the diagonal band (MS/VDB) in spatial working memory. The authors used a total of 0.5 µl of 0.12 µg/µl 192-Saporin injected into the MS/VDB to examine “environment-spatial” conditional learning. The findings suggest that cholinergic neurons of the MS/VDB are involved in some aspects of conditional associative learning.

Medullary serotonergic neurones and adjacent neurones that express neurokinin-1 receptors are both involved in chemoreception in vivo.

Nattie EE, Li A, Richerson GB, Lappi DA.

J Physiol 556(Pt 1):235-253, 2004.

The retrotrapezoid nucleus contains neurokinin-1 receptor (NK-1r)-expressing neurons that are involved in chemoreception. NK-1r-expressing neurons are also present in areas that contain medullary serotonergic neurons. These serotonergic neurons have been shown to be chemosensitive in vitro. With two 100-nl injections of 1 µM SP-SAP (Cat. #IT-07), anti-SERT-SAP (Cat. #IT-23), or both, the authors examined whether both cell populations are involved in chemoreception in vivo in rats. The results support that separate populations of serotonergic and NK-1r-expressing neurons are each involved in chemoreception in vivo.

Septohippocampal acetylcholine: involved in but not necessary for learning and memory?

Parent MB, Baxter MG.

Learn Mem 11(1):9-20, 2004.

In this review the authors describe some of the methods and rationale behind the investigation of hippocampal acetylcholine and its role in the support of learning and memory processes. Results produced by the use of 192-Saporin (Cat. #IT-01) are discussed, as well as the differences that have been found between the effects of 192-Saporin and those of less specific lesioning agents.

Extensive lesions of cholinergic basal forebrain neurons do not impair spatial working memory.

Vuckovich JA, Semel ME, Baxter MG.

Learn Mem 11(1):87-94, 2004.

The authors wished to examine whether cerebellar Purkinje cells damaged during a cholinergic basal forebrain lesion might be the cause of impaired working memory. Four injections of 0.2-0.3 µl (0.12-0.15 µg/ml, 192-Saporin, Cat. #IT-01) into the medial septum/vertical limb of the diagonal band, two injections into the horizontal limb of the diagonal band of Broca, and four injections into the nucleus basalis magnocellularis/ substantia innominata of rats were used to produce a very specific lesion. The results indicate that the cholinergic basal forebrain does not play a substantial role in spatial working memory.

Selective cholinergic denervation of the cingulate cortex impairs the acquisition and performance of a conditional visual discrimination in rats.

Winters BD, Robbins TW, Everitt BJ.

Eur J Neurosci 19(2):490-496, 2004.

Performance in conditional discrimination tasks is thought to be controlled at least in part by the cingulate cortex and its basal forebrain afferents. Using bilateral 0.5 µl injections of 0.02 µg/ml 192-Saporin (Cat. #IT-01) into the cingulate cortex of rats, the authors investigated the role of cholinergic projections from the vertical limb nucleus of the diagonal band to the cingulate cortex in specific types of learning. The results reinforce the idea that cholinergic projections to the cortex are involved in processing sensory information as well as task-related stimuli.

Increased calcium influx and ribosomal content correlate with resistance to endoplasmic reticulum stress-induced cell death in mutant leukemia cell lines.

Zhang Y, Berger SA.

J Biol Chem 279(8):6507-6516, 2004.

Ca2+ plays a vital role in many cell processes. To investigate events associated with Ca2+ and endoplasmic reticulum (ER) stress-induced cell death, the authors developed a mutant cell line with resistance to several ER stress-inducing agents. One of the assays used to define the characteristics of this cell line was treatment of the cells with 3 µg/ml of Saporin (Cat. #PR-01) and subsequent analysis of protein expression. The suppression of ribosome function partially reversed the resistance to ER stress-induced cell death.