2021 Targeting Trends Review

Duggan MR, Joshi S, Strupp J, Parikh V (2021) Chemogenetic inhibition of prefrontal projection neurons constrains top-down control of attention in young but not aged rats. Brain Struct Funct 226(7):2357-2373. doi: 10.1007/s00429-021-02336-2

Objective: To test the hypothesis that reduced PFC output would exert differential effects on attentional capacities in young and aged rats, with the latter exhibiting a more robust decline in performance.

Summary: There is a reduced efficiency of PFC-mediated top–down control of attention and cholinergic system in aging, and that activity of PFC output neurons does not reflect compensation in aged rats, at least in the attention domain.

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

See Also:

• Dalley JW et al. Cortical cholinergic function and deficits in visual attentional performance in rats following 192 IgG-Saporin-induced lesions of the medial prefrontal cortex. Cereb Cortex 14(8):922-932, 2004.
• Newman LA et al. Cholinergic deafferentation of prefrontal cortex increases sensitivity to cross-modal distractors during a sustained attention task. J Neurosci 28:2642-2650, 2008.
• Maddux JM et al. Dissociation of attention in learning and action: effects of lesions of the amygdala central nucleus, medial prefrontal cortex, and posterior parietal cortex. Behav Neurosci 121(1):63-79, 2007.

Barrett MJ, Murphy JM, Zhang J, Blair JC, Flanigan JL, Nawaz H, Dalrymple WA, Sperling SA, Patrie J, Druzgal TJ (2021) Olfaction, cholinergic basal forebrain degeneration, and cognition in early Parkinson disease. Parkinsonism Relat Disord 90:27-32. doi: 10.1016/j.parkreldis.2021.07.024

Summary: This study examined the relationship between olfaction, longitudinal change in cholinergic basal forebrain nuclei and their target regions, and cognition in early Parkinson’s Disease.

See: Linster C et al. Selective Loss of Cholinergic Neurons Projecting to the Olfactory System Increases Perceptual Generalization Between Similar, but Not Dissimilar, Odorants. Behav Neurosci 115(4):826-833, 2001.

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

Soma S, Suematsu N, Sato AY, Tsunoda K, Bramian A, Reddy A, Takabatake K, Karube F, Fujiyama F, Shimegi S (2021) Acetylcholine from the nucleus basalis magnocellularis facilitates the retrieval of well-established memory. Neurobiol Learn Mem 183:107484. doi: 10.1016/j.nlm.2021.107484

Summary: The authors tested the effect of a cholinesterase inhibitor, donepezil, on the retrieval of memory after a long no-task period in extensively trained rats. The results suggest that acetylcholine released from the NBM contributes to the retrieval of well-established memory developed by a daily routine.

Usage: Cholinergic neurons of the nucleus basalis magnocellularis (NBM) were lesioned with 192-IgG-SAP. NBM-lesioned rats showed severely impaired task initiation and performance. These abilities recovered as the trials progressed, though they never reached the level observed in rats with intact NBM. Saline with or without 192-IgG-SAP (0.3 μg in 1 μL, per site) was bilaterally injected into 2 sites of the NBM.

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

Jimenez-Martin J, Potapov D, Potapov K, Knöpfel T, Empson RM (2021) Cholinergic modulation of sensory processing in awake mouse cortex. Sci Rep 11(1):17525. doi: 10.1038/s41598-021-96696-8

Objective: To decipher the timing and significance of acetylcholine actions.

Summary: Study provides new insights into how the cortex processes sensory information and how loss of acetylcholine, for example in Alzheimer’s Disease, disrupts sensory behaviours.

Usage: Focal cortical injection of mu p75-SAP or Rabbit IgG-SAP (1.7 mg/ml, 0.3 µl total volume, rate 0.075 µl/minute).

Related Products: mu p75-SAP (Cat. #IT-16), Rabbit IgG-SAP (Cat. #IT-35)

Borkowski LF, Smith CL, Keilholz AN, Nichols NL (2021) Divergent receptor utilization is necessary for phrenic long-term facilitation over the course of motor neuron loss following CTB-SAP intrapleural injections. J Neurophysiol 126(3):709-722. doi: 10.1152/jn.00236.2021

Objective: The authors tested the hypothesis that phrenic long-term facilitation (pLTF) following treatment with CTB-SAP is: 1) adenosine 2A (A2A) receptor-dependent at 7d; and 2) serotonin (5-HT) receptor-dependent at 28d.

Summary: This study furthers understanding of the contribution of differential receptor activation to pLTF and its implications for breathing following respiratory motor neuron death.

Usage: Male rats received bilateral, intrapleural injections of CTB-SAP or Saporin Control (25 μg).

Related Products: CTB-SAP (Cat. #IT-14), Saporin (Cat. #PR-01)

Wiedlocha A, Haugsten EM, Zakrzewska M (2021) Roles of the FGF-FGFR signaling system in cancer development and inflammation. Cells 10(9):2231. doi: 10.3390/cells10092231

Objective: To highlight the latest advances in understanding the role of the FGF-FGFR signaling system in the development of neoplastic diseases and in the induction and maintenance of inflammation and its sequelae.

Related Products: FGF-SAP (Cat. #IT-38)

Sangartit W, Ha KB, Lee ES, Kim HM, Kukongviriyapan U, Lee EY, Chung CH (2021) Tetrahydrocurcumin ameliorates kidney injury and high systolic blood pressure in high-fat diet-induced type 2 diabetic mice. Endocrinol Metab (Seoul) 36(4):810-822. doi: 10.3803/EnM.2021.988 PMID: 34474516

Objective: To investigate the protective effect of tetrahydrocurcumin (THU) on intrarenal RAS expression, kidney injury, and systolic blood pressure (SBP) in high-fat diet (HFD)-induced type 2 diabetic mice.

Summary: THU alleviated kidney injury in mice with HFD-induced type 2 diabetes, possibly by blunting the activation of the intrarenal RAS/nicotinamide adenine dinucleotide phosphate oxidase IV (NOX4)/monocyte chemoattractant protein 1 (MCP-1) axis and by lowering the high SBP.

Usage: Western Blot (1:1000)

Related Products: Angiotensin II receptor (AT-2R) Rabbit Polyclonal, affinity-purified (Cat. #AB-N28AP)

Han D, Shi Y, Han F (2022) The effects of orexin-A and orexin receptors on anxiety- and depression-related behaviors in a male rat model of post-traumatic stress disorder. J Comp Neurol 530(3):592-606. doi: 10.1002/cne.25231

Objective: To determine the role of the orexin system in mediating anxiety- and depression-related behaviors in PTSD.

Summary: Intracerebroventricular administration of orexin-A alleviated behavioral changes in a PTSD rat model and partly restored the increased levels of OX1R in the medial prefrontal cortex (mPFC). These results suggest that the orexin system plays a role in the anxiety- and depression-related symptoms observed in PTSD.

See: Kaur S et al. Hypocretin-2 saporin lesions of the ventrolateral periaquaductal gray (vlPAG) increase REM sleep in hypocretin knockout mice. PLoS One 4:e6346, 2009.

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

Mori A, Cross B, Uchida S, Kerrick Walker J, Ristuccia R (2021) How are adenosine and adenosine A2A receptors involved in the pathophysiology of amyotrophic lateral sclerosis?. Biomedicines 9(8):1027. doi: 10.3390/biomedicines9081027

Objective: To examine potential biomarkers and the acute symptomatic pharmacology, including respiratory motor neuron control, of adenosine A2A receptor antagonism, and to explore the potential of the A2A receptor as a target for Amyotrophic Lateral Sclerosis (ALS) therapy.

Summary: CTB-SAP is listed in a table of experimental animal models of ALS. Intrapleural CTB-SAP injected rats (neurotoxic model of respiratory motor neuron death).

See: Seven YB et al. Adenosine 2A receptor inhibition protects phrenic motor neurons from cell death induced by protein synthesis inhibition. Exp Neurol 323:113067, 2020.

Related Products: CTB-SAP (Cat. #IT-14)

Llorca-Torralba M, Camarena-Delgado C, Suárez-Pereira I, Bravo L, Mariscal P, Garcia-Partida JA, López-Martín C, Wei H, Pertovaara A, Mico JA, Berrocoso E (2022) Pain and depression comorbidity causes asymmetric plasticity in the locus coeruleus neurons. Brain 145(1):154-167. doi: 10.1093/brain/awab239

Summary: There is strong comorbidity between chronic pain and depression. This study explores how this comorbidity occurs. The authors refer to published research that shows icv administration of anti-DBH-SAP or intra-LC administration of lidocaine dampened the evoked pain in conditions of long-term nerve-injury. However, icv injection of anti-DBH-SAP disrupts all noradrenergic nuclei (A1-A7), some of which contribute to sensorial hypersensitivity.

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

See Also:

• Brightwell JJ et al. Noradrenergic Neurons in the Locus Coeruleus Contribute to Neuropathic Pain. Neuroscience 160:174-185, 2009.
• Marques-Lopes J et al. The hyperalgesic effects induced by the injection of angiotensin II into the caudal ventrolateral medulla are mediated by the pontine A(5) noradrenergic cell group. Brain Res 1325:41-52, 2010.