References

Kruashvili L, Beselia G, Chkhikvishvili N (2019) Effect of medial septal selective and non selective lesions on exploratory behavior and recognition memory. Neuroscience 2019 Abstracts 336.01. Society for Neuroscience, Chicago, IL.

Summary: Investigation of cholinergic system and memory interaction has especially become the object of scientific attention due to the clinical and experimental data, in which the severity of dementia in Alzheimer’s disease (AD) was found to have a positive correlation with the extent of the cholinergic loss. The septum is connected to the hippocampus via the fimbria-fomix, which carries projections from the medial septum (MS), and the vertical limb of the diagonal band of Broca. These projections are predominantly cholinergic and GABAergic. Lesions of the fimbria-fomix, or electrolytic lesions of the MS, impair hippocampal- dependent learning and memory. The purpose of this study was to investigate ability to acquire and use spatial (or non-spatial) information as well as to habituate exploratory activity over time in sham-operated, electrolytic, neuro or immunotoxic MS lesioned rats. Methods: A total of 39 male rats were used. For electrolytic lesions a stainless steel was inserted in the MS. All injections were performed stereotaxically. Rats were individually given five 3-min sessions in the open field. All experiments were approved by the Animal Care and Use Committee of the Center and were in accordance with the principles of laboratory animal care. Results: Examination of the AChE stained sections showed that after injections of 192 IgG saporin into the MS, animals exhibited significantly less AChE staining in MS and hippocampus as compared to sections obtained from control animals. The MS electrolytic and ibotenic acid lesioned rats showed an increase in their exploratory activity to the objects and were impaired in habituating to the objects in the repeated spatial environment, rats with immunolesions of the MS did not differ from control rats. Electrolytic lesions of the MS disrupt spatial recognition memory, rats with immuno- or neurotoxic lesions of the MS were normal in detecting spatial novelty. The MS lesioned and control rats clearly reacted to the object novelty by exploring the new object more than familiar ones. Conclusions: MS is sufficient for spatial recognition, but is not sufficient for object recognition memory, the selective loss of septohippocampal cholinergic or noncholinergic projections does not disrupt the function of the hippocampus to a suffi cient extent to impair spatial recognition memory. Therefore, the present study demonstrates dissociation between the two major components (cholinergic and noncholinergic) of the septohippocampal pathway in exploratory behavior assessed in the open field.

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

Nazmuddin M, Rao HA, Van Laar T, Sarter MF (2019) How to stimulate: Basal forebrain DBS parameters to restore the attentional performance of rats with cholinergic losses. Neuroscience 2019 Abstracts 377.10. Society for Neuroscience, Chicago, IL.

Summary: The degeneration of basal forebrain (BF) cholinergic neurons is an index of the severity of cognitive impairment in Alzheimer disease (AD) and Parkinson’s disease (PD). Moreover, in PD patients, gait and balancing deficits, and an increased propensity for falls have been attributed to cholinergic losses. Thus, Deep Brain Stimulation (DBS) of the BF has been considered a potential therapeutic intervention to improve cognition and movement control in these patients. However, efficacy of BF DBS in clinical populations has yet to be conclusively demonstrated. Likewise, the demonstration of beneficial effects of BF DBS in rodent models has been hampered by uncertainties about useful animal models and behavioral tasks and, importantly, a lack of consensus concerning DBS parameters (duration, frequency, current, intermittent versus continuous, prior and/or during task, etc.). Here we assessed various DBS parameters in rats with a partial loss of the cortical cholinergic input system. In rats, such cholinergic losses have been frequently demonstrated to impair the detection of cues during the performance of a Sustained Attention Task (SAT) and to attenuate performance recovery following a distractor challenge (dSAT). In PD patients with cholinergic losses, attentional impairments were also attributed to cortical and thalamic cholinergic losses (Kim et al., 2017). The attribution of SAT impairments to cholinergic losses is consistent with evidence showing that the detection of cues and associated attentional control parameters depend on cortical cholinergic signaling (e.g., Howe et al., 2017). Here, rats acquired the SAT, received infusions of the cholino-specific neurotoxin 192-IgG-saporin into the BF, and were implanted bilaterally with BF unipolar stimulation electrodes. Initial DBS parameters consisted of continuous high (130 Hz) versus low (20 Hz) frequency stimulation, intermittent (20-s ON at 80 Hz and 40-s OFF) stimulation, with pulse width and amplitude kept constant at 100 µs and 100 µA, respectively. We first assessed the effects of these DBS parameters on the behavior of rats in an open field space and then when administered during, or only prior to (for 1 hr), SAT and dSAT performance. Ongoing experiments indicate that these stimulation parameters are well tolerated as indicated by the absence of effects on locomotor and exploratory activity. We predict that BF DBS will be particularly effective in restoring attentional performance in the dSAT condition. If confirmed, this finding will suggest that demonstration of efficacy in patients will require measures indicating their attentional capacities in response to taxing performance challenges.

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

Blumenthal SA, Maness EBL, Fadel JR, Burk JA (2019) Effects of an orexin-2 receptor agonist on attention in rats following loss of cortical cholinergic projections. Neuroscience 2019 Abstracts 418.06. Society for Neuroscience, Chicago, IL.

Summary: Deterioration to the basal forebrain cholinergic system (BFCS) is linked to age-related cognitive impairment, specifically to the pathology of Alzheimer’s disease (AD). Animals with BFCS damage perform poorly on learning, memory, and attention tasks, indicating cognitive deficits. The orexin neuropeptide system, comprised of two neuropeptides (orexin A and orexin B), has also been implicated in the cognitive decline associated with aging, likely due to the role of orexins in promoting attention. Two orexin receptor subtypes exist, orexin 1 (Ox1R) and orexin 2 (Ox2R). Studies have examined the effects of stimulation and blockage of both receptors together and Ox1R alone on attention; but no studies have examined the role of Ox2Rs in attention through the use of Ox2R agonists. Ox2Rs may be implicated in attentional processes and the loss of orexin neurons seen in age-related cognitive decline. In order to examine the role of Ox2Rs in attention following BFCS deterioration, the present study administered the Ox2R agonist, YNT-185, to rats given intrabasalis infusions of either saline (n = 12) or 192 IgG saporin (n=11), an immunotoxin which selectively destroys the BFCS. Animals received infusions of YNT-185 to the lateral ventricle (LV) in doses of 0, 1, 10, and 100nM across four separate sessions and performance was then assessed on a sustained attention task requiring discrimination between signal and non-signal trials through lever presses. The 100nM dose of YNT-185 improved attentional performance, as compared to the 0nM dose, for rats given the immunotoxin, but worsened performance for rats given saline lesions. YNT-185 may be efficacious in aiding attentional function in animals with vulnerable cholinergic systems but may lead to overexcitation for those with intact cholinergic function.

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

Guyenet PG, Stornetta RL, Souza GMPR, Abbott SBG, Shi Y, Bayliss DA. (2019) The retrotrapezoid nucleus: Central chemoreceptor and regulator of breathing automaticity. Trends Neurosci 42(11):807-824. doi: 10.1016/j.tins.2019.09.002

Summary: This review describes the neurons of the retrotrapezoid nucleus (RTN), their transcriptome, developmental lineage, and anatomical projections. The authors also review their contribution to CO2 homeostasis and to the regulation of breathing automaticity during sleep and wake.

Usage: Local injection of SSP-SAP to kill RTN neurons.

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

Li J, Xiang X, Xu H, Shi Y (2019) Cilostazol promotes angiogenesis and increases cell proliferation after myocardial ischemia–reperfusion injury through a camp-dependent mechanism. Cardiovasc Eng Technol 10(4):638-647. doi: 10.1007/s13239-019-00435-0 PMID: 31625080

Usage: western

Related Products: Fibroblast Growth Factor Rabbit Polyclonal, mammalian (Cat. #AB-07)

Kucinski A, Phillips KB, Koshy Cherian A, Sarter M (2020) Rescuing the attentional performance of rats with cholinergic losses by the M1 positive allosteric modulator TAK-071. Psychopharmacology (Berl) 237(1):137-153. doi: 10.1007/s00213-019-05354-5 PMID: 31620809

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

Avrampou K, Pryce KD, Ramakrishnan A, Sakloth F, Gaspari S, Serafini RA, Mitsi V, Polizu C, Swartz C, Ligas B, Richards A, Shen L, Carr FB, Zachariou V (2019) RGS4 maintains chronic pain symptoms in rodent models. J Neurosci 39(42):8291-8304. doi: 10.1523/JNEUROSCI.3154-18.2019 PMID: 31308097

Usage: western

Related Products: Metabotropic Glutamate Receptor 2 (mGluR2) Mouse Monoclonal (Cat. #AB-N32)

Wercberger R, Basbaum AI (2019) Spinal cord projection neurons: A superficial, and also deep, analysis. Curr Opin Physiol 11:109-115. doi: 10.1016/j.cophys.2019.10.002

Summary: Modern approaches to map complex neural circuits require knowledge of the molecular language that defines cell type specificity. However, with few exceptions, NK1R remains the marker consistently used to define projection neurons and even to interrogate their contribution to pain and itch (Mantyh et al.) The first of two studies demonstrating that SP-SAP-mediated ablation of dorsal horn NK1R-expressing neurons reduces injury-induced hyperalgesia. (Carstens et al.) In this paper SP-SAP-mediated ablation of dorsal horn NK1R-expressing neurons reduced pruritogen-evoked scratching.

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

See Also:

• Mantyh PW et al. Inhibition of hyperalgesia by ablation of lamina I spinal neurons expressing the substance P receptor. Science 278:275-279, 1997.
• Carstens EE et al. Dorsal horn neurons expressing NK-1 receptors mediate scratching in rats. Neuroreport 21:303-308, 2010.

Murillo-Rodríguez E, Millán-Aldaco D, Palomero-Rivero M, Morales-Lara D, Mechoulam R, Drucker-Colín R (2019) Cannabidiol partially blocks the excessive sleepiness in hypocretindeficient rats: Preliminary data. CNS Neurol Disord Drug Targets 18(9):705-712. doi: 10.2174/1871527318666191021143300

Objective: To determine whether the systemic injection of CBD (5 mg/kg, i.p.) would block the excessive sleepiness in a narcoleptic model.

Summary: Preliminary findings suggest that CBD might prevent sleepiness in narcolepsy.

Usage: Orexin-SAP (490 ng/0.5 μL, n= 10) was bilaterally injected into the LH of rats to eliminate HCRT leading to the establishment of narcoleptic-like behavior.

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

Martins JR, Reichhart N, Kociok N, Stindl J, Foeckler R, Lachmann P, Todorov V, Castrop H, Strauß O (2019) Systemic ß adrenergic stimulation/ sympathetic nerve system stimulation influences intraocular RAS through cAMP in the RPE. Exp Eye Res 189:107828. doi: 10.1016/j.exer.2019.107828 PMID: 31589840

Objective: To investigate whether systemic β-adrenergic stimulation of the retinal pigment epithelium (RPE) also modulates renin expression in the RPE.

Summary: In vitro analysis of renin gene expression using polarized porcine RPE showed that the activity of the renin promoter can be increased by cAMP stimulation (IBMX/forskolin) but was not influenced by angiotensin-2.

Usage: Immunohistochemistry; eye sections were labeled overnight at 4°C with Anti-AT-1R.

Related Products: Angiotensin II receptor (AT-1R) Rabbit Polyclonal, affinity-purified (Cat. #AB-N27AP)