Targeting Tools: Anti-ChAT-SAP

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Choline acetyltransferase (ChAT) catalyzes the synthesis of the neurotransmitter acetylcholine (ACh) from choline and acetyl-CoA in cholinergic neurons. ChAT serves as a specific marker for cholinergic neurons in both peripheral and central nervous systems. Evidence shows that ChAT exists in two forms inside cholinergic nerve terminals, a soluble hydrophilic form and the membrane-associated amphiphilic form.[1-2] Membrane-bound ChAT has served as the feature condition that allows specific targeting with an affinity-purified antibody to ChAT conjugated to saporin to specifically target and eliminate those specific cells. Anti-ChAT-SAP (Cat. #IT-42) is made with an antibody using a 22-amino acid peptide from porcine ChAT.

The targeted toxin has been shown in several papers to eliminate cholinergic neurons in the rat brain[3-6] (also see Cover Article) and is expected to cross-react with mouse, and many other species.

Representative sections of ChAT-immunostained tissues of N.Acc. from rats that (A and C) received an intra-accumbens micro-injection of Rabbit IgG-SAP (Cat. #IT-35; 250 ng; control), and (B and D) received an intra-accumbens micro-injection of Anti-ChAT-SAP (250 ng). Administration of Anti-ChAT-SAP reduced significantly the amount of cholinergic interneurons at the injection site while sparing adjacent areas. Scales A and B = 200 μm; C and D = 1 mm; ac: anterior commissure.

François LaPlante. Targeting Trends, 2013. 14(1): p. 1,6.

References:

  1. Gabrielle P1, Jeana M, Lorenza EC.Laplante F, Dufresne MM, Ouboudinar J, Ochoa-Sanchez R, Sullivan RM. (2013) Cytosolic choline acetyltransferase binds specifically to cholinergic plasma membrane of rat brain synaptosomes to generate membrane-bound enzyme. Neurochem Res 28(3-4):543-549.
  2. Smith CP, Carroll PT. (1980) A comparison of solubilized and membrane bound forms of choline-O-acetyltransferase (EC 2.3.1.6) in mouse brain nerve endings. Brain Res 185(2):363-371.
  3. Aoki S, Liu AW, Zucca A, Zucca S, Wickens JR. (2015) Role of striatal cholinergic interneurons in set-shifting in the rat. J Neurosci 35(25):9424-9431.
  4. Laplante F, Dufresne MM, Ouboudinar J, Ochoa-Sanchez R, Sullivan RM. (2013) Reduction in cholinergic interneuron density in the nucleus accumbens attenuates local extracellular dopamine release in response to stress or amphetamine. Synapse 67(1):21-29.
  5. Laplante F, Zhang ZW, Huppe-Gourgues F, Dufresne MM, Vaucher E, Sullivan RM. (2012) Cholinergic depletion in nucleus accumbens impairs mesocortical dopamine activation and cognitive function in rats. Neuropharmacology 63(6):1075-1084.
  6. Laplante F, Lappi DA, Sullivan RM (2011) Cholinergic depletion in the nucleus accumbens: Effects on amphetamine response and sensorimotor gating. Prog Neuropsychopharmacol Biol Psychiatry 35(2):501-509.
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