Targeting Topics 03q1

Basal forebrain cholinergic neurons are necessary for estrogen to enhance acquisition of a delayed matching-to-position T-maze task.

Gibbs RB.

Horm Behav 42(3):245-257, 2002.

The author investigated the role of cholinergic neurons of the basal forebrain in cognitive function using a long-term hormone replacement model in rats. Septal infusions of either 1.0 μg or 0.22 μg 192-Saporin (Cat. #IT-01) prevented the therapeutic effects of hormone replacement on cognitive function.

Long-term plastic changes in galanin innervation in the rat basal forebrain.

Hartonian I, Mufson EJ, De Lacalle S.

Neuroscience 115(3):787-795, 2002.

One hallmark of Alzheimer’s disease is the hyperinnervation of surviving cholinergic basal forebrain neurons with galanin-IR fibers. This may exacerbate the cholinergic deficit. The authors injected 192-Saporin (140 nl of 0.075 mg/ml, Cat. #IT-01) into the diagonal band of Broca of rats. An increase in galanin immunoreactivity was observed as early as 1 hour post-injection, and persisted as long as 6 months.

Effects of cholinergic lesions produced by infusions of 192 IgG-saporin on glucocorticoid receptor mRNA expression in hippocampus and medial prefrontal cortex of the rat.

Helm KA, Han JS, Gallagher M.

Neuroscience 115(3):765-774, 2002.

The authors investigated the loss of cholinergic support from the basal forebrain, a hallmark of aging, on glucocorticoid receptor mRNA expression in various target sites. 192-Saporin (Cat. #IT-01) was injected into either the nucleus basalis magnocellularis/substantia innominata (0.2 μl of 0.25 mg/ml) or the medial septum/vertical limb of the diagonal band (0.3 μl of 0.25 mg/ml). Treated rats sustained a significant decrease in glucocorticoid receptor mRNA levels in the hippocampus and medial prefrontal cortex.

Changes in activity and expression of phosphofructokinase in different rat brain regions after basal forebrain cholinergic lesion.

Zeitschel U, Schliebs R, Rossner S, Bigl V, Eschrich K, Bigl M.

J Neurochem 83(2):371-380, 2002.

The authors used intraventricular injections of 4 μg of 192-Saporin (Cat. #IT-01) in rats to investigate whether impaired cholinergic transmission may cause metabolic changes. Although the results demonstrate an initial increase in a cortical glucose metabolic marker, this increase was transient. The authors conclude that cholinergic systems do not control cortical glucose metabolic mechanisms affected by Alzheimer’s disease.

Early neonatal 192 IgG saporin induces learning impairments and disrupts cortical morphogenesis in rats.

Ricceri L, Hohmann C, Berger-Sweeney J.

Brain Res 954(2):160-172, 2002.

Previous data have shown that cholinergic lesions on postnatal day (pnd) 7 in rats produce learning impairments on pnd 15. Using 0.2 μg injections of 192-Saporin (Cat. #IT-01) into the lateral ventricles, the authors investigated the effect of lesioning animals at pnd 1 and 3. The treated animals demonstrated sex-specific deficits in some cognitive behaviors, as well as changes in neurochemistry and cortical organization.

Selective lesions of basal forebrain cholinergic neurons produce anterograde and retrograde deficits in a social transmission of food preference task in rats.

Vale-Martinez A, Baxter MG, Eichenbaum H.

Eur J Neurosci 16(6):983-998, 2002.

Injections of 0.2 μg 192-Saporin (Cat. #IT- 01) were made into either the medial septum/vertical limb of the diagonal band (MS/VDB), or the nucleus basalis magnocellularis/substantia innominata (NBM/SI) of rats. MS/VDB lesions had no effect on anterograde memory, while NBM/SI lesions strongly impaired immediate and 24-hour retention. In contrast, MS/DVB lesions produced significant memory deficits in a long-delay retrograde memory test.

Substance P-saporin lesion of neurons with NK1 receptors in one chemoreceptor site in rats decreases ventilation and chemosensitivity.

Nattie EE, Li A.

J Physiol 544(Pt 2):603-616, 2002.

The authors injected 0.1 pmol SP-SAP (Cat. #IT-07) into the retrotrapezoid nucleus/parapyramidal region of rats. The lesioned animals demonstrated hypoventilation while at rest, decreased response to high CO2 levels, and a tendency to sleep less.

Efferent projections from the striatal patch compartment: anterograde degeneration after selective ablation of neurons expressing mu-opioid receptor in rats.

Tokuno H, Chiken S, Kametani K, Moriizumi T.

Neurosci Lett 332(1):5-8, 2002.

Taking advantage of the fact that neurons in patch compartments of the striatum express μ-opioid receptors, the authors injected 8.5 ng of dermorphin-SAP (Cat. #IT-12) into the striatum of rats. This lesion produced a degeneration of patch neurons as well as anterograde degeneration of efferent fibers from patch compartments, allowing further elucidation of the functional organization of the striatum.

Selective immunolesioning of the basal forebrain cholinergic neurons in rats: effect on attention using the 5-choice serial reaction time task.

Risbrough V, Bontempi B, Menzaghi F.

Psychopharmacology (Berl) 164(1):71-81, 2002.

The authors used 0.067 μg injections of 192- Saporin (Cat. #IT-01) into the nucleus basalis magnocellularis to investigate attentional performance in rats. The treated animals exhibited a very specific subset of attentional deficits, many centered around increased difficulty completing tasks in the presence of distractions.

Spinal neurons that possess the substance P receptor are required for the development of central sensitization.

Khasabov SG, Rogers SD, Ghilardi JR, Peters CM, Mantyh PW, Simone DA.

J Neurosci 22(20):9086-9098, 2002.

Using 5 x 10-5 intrathecal injections of SP-SAP (Cat. #IT-07) the authors examined the role of SPR-expressing neurons in modulation of pain and hyperalgesia. Treated animals exhibited highly attenuated sensitization to stimuli after capsaicin treatment as compared to controls, but normal responses in the absence of capsaicin.

In vivo labeling of rabbit cholinergic basal forebrain neurons with fluorochromated antibodies.

Hartig W, Varga C, Kacza J, Grosche J, Seeger J, Luiten PG, Brauer K, Harkany T.

Neuroreport 13(11):1395-1398, 2002.

To investigate in vivo labeling of p75 low- affinity neurotrophin receptor the authors conjugated Cy3 to ME20.4 (Cat. # ABN07) and performed either unilateral or bilateral icv injections in rabbits. The antibody labeled only cholinergic neurons demonstrating its potential as a p75 marker.

Reactivity to object and spatial novelty is normal in older Ts65Dn mice that model Down syndrome and Alzheimer’s disease.

Hyde LA, Crnic LS.

Brain Res 945(1):26-30, 2002.

The authors hypothesized that a mouse model for Down syndrome may show some of the same cognitive deficits exhibited by rats lesioned with 192-Saporin (Cat. #IT-01), which eliminates cholinergic cells in the basal forebrain. The results suggest that in this Down syndrome model, cell loss has a much greater cognitive effect if it happens early in development as opposed to in adulthood.

Motoneuron-derived neurotrophin-3 is a survival factor for PAX2-expressing spinal interneurons.

Bechade C, Mallecourt C, Sedel F, Vyas S, Triller A.

J Neurosci 22(20):8779-8784, 2002.

In the rat, half of motoneurons die between embryonic day 15 and postnatal day 1. Programmed cell death of interneurons is not as well characterized. The authors cultured explants of brachial neural tubes from rat embryos in the presence of 200 ng/ml of 192-Saporin (Cat. #IT-01). Although 192- Saporin had no direct effect on interneurons in culture, elimination of p75-neurotrophin receptor-expressing neurons caused the interneurons to die.

Effect of 192 IgG-saporin on circadian activity rhythms, expression of P75 neurotrophin receptors, calbindin-D28K, and light-induced Fos in the suprachiasmatic nucleus in rats.

Beaule C, Amir S.

Exp Neurol 176(2):377-389, 2002.

The authors used bilateral icv injections of 200 ng of 192-Saporin (Cat. #IT-01) to NTR investigate the contribution of p75-expressing neurons to the determination of a circadian rhythm. The data show that NTR p75 -expressing neurons are not essential for this process.

Rivastigmine antagonizes deficits in prepulse inhibition induced by selective immunolesioning of cholinergic neurons in nucleus basalis magnocellularis.

Ballmaier M, Casamenti F, Scali C, Mazzoncini R, Zoli M, Pepeu G, Spano PF.

Neuroscience 114(1):91-98, 2002.

The authors injected 300 nl of 400 ng/μl 192-Saporin (Cat. #IT-01) bilaterally into the nucleus basalis magnocellularis of rats, then treated the lesioned animals with rivastigmine, a cholinesterase inhibitor. Animals treated with rivistagmine exhibited raised levels of cortical acetylcholine, in contrast to undetectable acetylcholine levels in lesioned animals not treated with rivastigmine.

Mnemonic deficits in animals depend upon the degree of cholinergic deficit and task complexity.

Pizzo DP, Thal LJ, Winkler J.

Exp Neurol 177(1):292-305, 2002.

In this study, the authors compared icv and intraparenchymal injections of 192-Saporin (Cat. #IT-01, 3.3 μg and 450 ng, respectively). While a similar reduction in choline acetyltransferase activity was observed with each strategy, and performance in certain allocentric tasks was similar, an egocentric task showed a marked difference between the two groups.