targeted-toxins

Stornetta RL, Rosin DL, Wang H, Sevigny CP, Weston MC, Guyenet PG (2003) A group of glutaminergic interneurons expressing high levels of both neurokinin-1 receptors and somatostatin identifies the region of the pre-Bötzinger complex. J Comp Neurol 455(4):499-512. doi: 10.1002/cne.10504

Summary: 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.

Related Products: SSP-SAP (Cat. #IT-11)

Berntson GG, Shafi R, Sarter M (2002) Specific contributions of the basal forebrain corticopetal cholinergic system to electroencephalographic activity and sleep/waking behaviour. Eur J Neurosci 16(12):2453-2461. doi: 10.1046/j.1460-9568.2002.02310.x

Summary: 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.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Silveira DC, Cha BH, Holmes GL (2002) Effects of lesions of basal forebrain cholinergic neurons in newborn rats on susceptibility to seizures. Dev Brain Res 139:277-283. doi: 10.1016/s0165-3806(02)00586-2

Summary: 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.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Hartonian I, Mufson EJ, de Lacalle S (2002) Long-term plastic changes in galanin innervation in the rat basal forebrain. Neuroscience 115(3):787-795. doi: 10.1016/s0306-4522(02)00453-0

Summary: 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.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Helm KA, Han JS, Gallagher M (2002) 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. Neuroscience 115(3):765-774. doi: 10.1016/s0306-4522(02)00487-6

Summary: 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.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Riley J, Lin LH, Chianca DA, Talman WT (2002) Ablation of NK1 receptors in rat nucleus tractus solitarii blocks baroreflexes. Hypertension 40(6):823-826. doi: 10.1161/01.hyp.0000042089.34004.cf

Summary: 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.

Related Products: SP-SAP (Cat. #IT-07)

Ricceri L, Hohmann C, Berger-Sweeney J (2002) Early neonatal 192 IgG saporin induces learning impairments and disrupts cortical morphogenesis in rats. Brain Res 954(2):160-172. doi: 10.1016/s0006-8993(02)03172-4

Summary: 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.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Wang H, Guyenet PG (2002) Neurokinin-1 receptor immunoreactive (NK1R-ir) neurons control caudal ventrolateral medulla (VLM) gabaergic depressor neurons. Neuroscience 2002 Abstracts 862.4. Society for Neuroscience, Orlando, FL.

Summary: Depressor responses to injection of DL-homocysteic acid (DLH) into the caudal VLM are attenuated after selective unilateral lesion of the NK1R-ir cells of the VLM with a saporin-NK1R agonist conjugate (SSP-SAP)(Wang et al., J. Neurosci 2002). Here we tested whether SSP-SAP treatment destroys caudal VLM depressor GABAergic neurons thereby causing loss of DLH-induced sympathoinhibition. Two weeks after unilateral lesion of VLM NK1R-ir cells (97% reduction without loss of catecholaminergic neurons), DLH (5-10 nl, 10mM) was injected into multiple regions of the caudal and rostral VLM on both sides of the brain. The decrease in BP and sympathetic tone (SND) caused by DLH injections into caudal VLM were blunted on the lesioned side vs the intact side (p<.05, N = 7). The rise in BP and SND caused by DLH injection into rostral VLM were normal on both sides. To determine if the GABAergic barosensitive cells of the caudal VLM express NK1R, conscious rats were infused with L-phenylephrine (PE) (7μg/min, for 25 min) or saline. PE infusion raised BP by 25% and decreased HR 27% (mean; N= 4). Saline infusion produced no effect. Fos-ir neurons were mapped throughout the VLM. The caudal VLM of PE-treated rats contained many more Fos-ir cells than that of the saline controls (128.7 ± 4.2 vs. 18.7 ± 1.6, N= 4). Caudal VLM Fos-ir neurons were not NK1R-ir in either group of rats. In conclusion, the baroreceptor-activated GABAergic neurons of the caudal VLM are not NK1R-ir. The data suggests that NK1R-ir cells might provide an excitatory drive to the caudal VLM barosensitive neurons (HL 28785 to PGG).

Related Products: SSP-SAP (Cat. #IT-11)

Nagle RA, Liberatore MA, Zombon NJ, Pokala VN, Li PK, Pokala VN, Johnson DA (2002) Effect of selective cholinergic lesioning of basal forebrain with 192 IgG-saporin on neurotransmitter concentrations in hippocampus of rat. Neuroscience 2002 Abstracts 880.6. Society for Neuroscience, Orlando, FL.

Summary: In vivo microdialysis techniques were used to examine the effects of lesioning of cholinergic neurons of the medial septum using the selective cholinergic neurotoxin 192-IgG-Saporin (SAP), on hippocampal acetylcholine (ACh), glutamate and GABA in adult male Sprague Dawley rats. High and low (1.0 and 0.22 μg) doses of SAP were used for infusion into the basal forebrain. SAP treated rats showed a significant dose dependent decrease of 74% and 59% in ACh for the high and low doses respectively, compared to controls. Glutamate decreased 50% in animals treated with 0.22 μg SAP. The data suggest that lesioning of basal forebrain neurons with SAP results in changes in neurotransmitter concentrations in the hippocampus.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Watts AG, Sanchez-Watts G, Dinh TT, Ritter S (2002) Immunotoxic lesions of ascending catechoalminergic afferents abolish the CRH gene transcriptional response to 2-deoxyglucose in the rat paraventricular nucleus. Neuroscience 2002 Abstracts 865.2. Society for Neuroscience, Orlando, FL.

Summary: CRH neurons in the medial parvicellular (mp) part of the paraventricular nucleus (PVH) are critical for the neural control of the hypothalamo-pituitary-adrenal axis. One of their most prominent afferents sets derives from hindbrain catecholaminergic neurons that are thought to help mediate viscerosensory influences on the PVHmp. Despite the prominence of this input, its precise role in controlling CRH neuronal function remains controversial. Here we report the effect on basal and stimulated CRH gene expression of an immunotoxin that selectively destroys catecholaminergic neurons. Rats were injected in the PVH with either a saporin-anti-dopamine B-hydroxylase (DBH) conjugate (DSAP), which leads to total loss of DBH immunoreactivity in the PVH, or saporin alone (SAP), which does not. Three weeks later, animals were injected either with 250mg/kg of 2-deoxy-D-glucose (2DG) or vehicle. Thirty mins later they were anesthetized and perfused with 4% buffered paraformaldehyde. Fifteen um frozen sections were cut through the hypothalamus and hybridized for CRH mRNA, CRH hnRNA, or c-fos mRNA. DSAP treatment had no effect on CRH mRNA levels in the PVH of vehicle- or 2DG-injected animals, but abolished the CRH hnRNA and c-fos mRNA responses to 2DG. We have reported elsewhere that DSAP lesions selectively abolish the corticosterone response to 2DG, but not to swim stress, or circadian corticosterone release. We now show that catecholaminergic afferents are required for 2DG-induced CRH gene expression, but not for basal expression.

Related Products: Anti-DBH-SAP (Cat. #IT-03)