2007 Targeting Trends Review

Fletcher BR, Baxter MG, Guzowski JF, Shapiro ML, Rapp PR (2007) Selective cholinergic depletion of the hippocampus spares both behaviorally induced Arc transcription and spatial learning and memory. Hippocampus 17:227-234. doi: 10.1002/hipo.20261

Summary: The immediate early gene Arc is required for long-term synaptic changes and memory consolidation. The authors lesioned the fornix to examine cholinergic contributions of the medial septum and the vertical diagonal band to spatial learning impairments and behavioral induction of Arc transcription. 0.24-0.36 µg of 192-IgG-SAP (Cat. #IT-01) was delivered to the fornix of rats. Results from various water-maze tasks indicate that spatial learning deficits and impaired Arc transcription associated with lesions of the fornix are not caused by cholinergic deafferentation.

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

Truitt WA, Sajdyk TJ, Dietrich AD, Oberlin B, McDougle CJ, Shekhar A (2007) From anxiety to autism: spectrum of abnormal social behaviors modeled by progressive disruption of inhibitory neuronal function in the basolateral amygdala in Wistar rats. Psychopharmacology (Berl) 191(1):107-118. doi: 10.1007/s00213-006-0674-y

Summary: The amygdala has been identified as being involved in social behaviors. Six 4 ng injections of SSP-SAP (Cat. #IT-11) were administered bilaterally into the basolateral nucleus (BLA) of the amygdala of rats. Blank-SAP (Cat. #IT-21) was used as a control. Results of a social interaction paradigm suggest that in normal animals social inhibition can be overcome by habituation. In lesioned animals, however, social inhibition is not reversed by habituation, indicating that NK-1 receptor-expressing GABAergic interneurons in the BLA are important in this system.

Related Products: SSP-SAP (Cat. #IT-11), Blank-SAP (Cat. #IT-21)

Yip WL, Weyergang A, Berg K, Tonnesen HH, Selbo PK (2007) Targeted delivery and enhanced cytotoxicity of cetuximab-saporin by photochemical internalization in EGFR-positive cancer cells. Mol Pharm 4(2):241-251. doi: 10.1021/mp060105u

Summary: Photochemical internalization (PCI) releases macromolecules from endocytic vesicles using photosensitizer activation by light. This technique allows the release of endocytosed molecules before degradation occurs in the lysosome. The authors demonstrate the proof-of-concept for this technique by combining biotinylated cetuximab (a chimeric monoclonal antibody to the EGFr) with streptavidin-ZAP (Cat. #IT-27). The conjugate was applied to three different human cancer cell lines, demonstrating enhanced specificity and toxicity against cells expressing the EGFr.

Related Products: Streptavidin-ZAP (Cat. #IT-27)

Furlong T, Carrive P (2007) Neurotoxic lesions centered on the perifornical hypothalamus abolish the cardiovascular and behavioral responses of conditioned fear to context but not of restraint. Brain Res 1128(1):107-119. doi: 10.1016/j.brainres.2006.10.058

Summary: This work examined the role of orexin-containing neurons in the perifornical hypothalamus (PeF) during stress response. Orexin-SAP (Cat. #IT-20) or the control conjugate blank-SAP (Cat. #IT-21) was injected into the PeF of pre-conditioned rats. Tests measuring restraint and conditioned fear to context were then performed on the lesioned animals. While the lesioning was not specific enough to connect results to orexin-containing neurons, the data indicate that the PeF is critical for some forms of stress, but not others.

Related Products: Orexin-B-SAP (Cat. #IT-20), Blank-SAP (Cat. #IT-21)

Dwyer TA, Servatius RJ, Pang KC (2007) Noncholinergic lesions of the medial septum impair sequential learning of different spatial locations. J Neurosci 27:299-303. doi: 10.1523/JNEUROSCI.4189-06.2007

Summary: The medial septum and the vertical limb of the diagonal band of Broca (MSDB) have extensive connections to the hippocampus. In general, impairments due to loss of cholinergic neurons in this area have been smaller than those due to the loss of noncholinergic neurons. The authors treated rats with either 192-IgG-SAP (Cat. #IT-01) or kainic acid into each hemisphere of the medial septum. Behavioral testing following surgery demonstrated that the animals with noncholinergic lesions had impaired performance, even when compared to the animals with cholinergic lesions.

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

Walker BR, Diefenbach KS, Parikh TN (2007) Inhibition within the nucleus tractus solitarius (NTS) ameliorates environmental exploration deficits due to cerebellum lesions in an animal model for autism. Behav Brain Res 176(1):109-120. doi: 10.1016/j.bbr.2006.08.008

Summary: In this work the authors use environmental exploration deficits in rats as a model for autism. Animals received 2 µg of either OX7-SAP (Cat. #IT-02) or 192-Saporin (Cat. #IT-01) into each ventricle. Only the OX7-SAP treated rats displayed a reduction in exploration behavior, and the anticonvulsant muscimol restored exploration behavior to control levels. This system may have use in controlling behavior deficits seen in autism.

Related Products: 192-IgG-SAP (Cat. #IT-01), OX7-SAP (Cat. #IT-02)

Ma W, Eisenach JC (2007) Neuronal nitric oxide synthase is upregulated in a subset of primary sensory afferents after nerve injury which are necessary for analgesia from alpha2-adrenoceptor stimulation. Brain Res 1127(1):52-58. doi: 10.1016/j.brainres.2006.10.008

Summary: Peripheral nerve injury resulting in neuropathic pain often responds poorly to opioid treatment. alpha2-adrenoreceptor (AR) agonists, however, perform better after this type of injury. After a spinal nerve ligation, rats were treated with a 0.6 µg-intrathecal injection of 192-saporin (Cat. #IT-01). The increase of neuronal nitric oxide synthase (nNOS) caused by spinal ligation was abolished in the lesioned animals. The data indicate that AR agonists may reduce sensitization by activating nNOS fibers in the superficial dorsal horn.

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

Ohtori S, Inoue G, Koshi T, Ito T, Doya H, Moriya H, Takahashi K (2006) Substance P-saporin down-regulates substance P receptor immunoreactive sensory dorsal root ganglion neurons innervating the lumbar intervertebral discs in rats. Spine 31:2987-2991. doi: 10.1097/01.brs.0000250306.12996.fa

Summary: Neurokinin-1 (NK-1) receptor expressing neurons that innervate lumbar intervertebral discs may be involved in lower back pain. Here the authors investigate the basic effect of SP-SAP (Cat. #IT-07) on neurons innervating the L5/6 intervertebral disc. Rats were injected with 175 ng of SP-SAP. The number of NK-1 receptor expressing neurons was reduced by over 75% in the treated animals, demonstrating SP-SAP as a useful tool to investigate the mechanism of discogenic low back pain, particulary for investigating behavioral impacts.

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

Cabrera SM, Chavez CM, Corley SR, Kitto MR, Butt AE (2006) Selective lesions of the nucleus basalis magnocellularis impair cognitive flexibility. Behav Neurosci 120:298-306. doi: 10.1037/0735-7044.120.2.298

Summary: In humans, one aspect of cognitive flexibility is being able to shift attention under a variety of pressures. Here the authors suggest that lesions to the cholinergic nucleus basalis magnocellularis (NBM) will impair cognitive flexibility. The NBM of rats was lesioned with 0.08 µg of 192-IgG-SAP (Cat. #IT-01). Both lesioned and controlled animals displayed a similar ability to learn a discrimination task, but lesioned animals displayed perseveration – the uncontrollable repetition of a previously correct response – indicating a loss of cognitive flexibility.

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

Vera-Portocarrero LP, Zhang ET, King T, Ossipov MH, Vanderah TW, Lai J, Porreca F (2007) Spinal NK-1 receptor expressing neurons mediate opioid-induced hyperalgesia and antinociceptive tolerance via activation of descending pathways. Pain 129:35-45. doi: 10.1016/j.pain.2006.09.033

Summary: Administration of opioids can induce hyperalgesia in humans and other mammals. In this work the authors examined the role of NK-1 receptor-expressing neurons in the spinal dorsal horn during a hyperalgesic condition not induced by tissue injury. 5 µl of 10 µM SP-SAP (Cat. #IT-07) was injected into the intrathecal space of rats. Saporin (Cat. #PR-01) was used as a control. Osmotic pumps then delivered morphine. Data from the lesioned animals indicate that NK-1 receptor-expressing neurons play a critical role in this hyperalgesic circuit.

Related Products: SP-SAP (Cat. #IT-07), Saporin (Cat. #PR-01)