Eliminating CBF Neurons

as seen in Targeting Trends Newsletter, Jul-Aug-Sep 2004

   
   
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What dosage of 192-Saporin (192-IgG-SAP, Cat. #IT-01) should be used in the lateral ventricle to eliminate cholinergic neurons in the basal forebrain, including substantia innominata (SI)? I read that Calza et al [1] used 2 or 3 micrograms/4.5 ┬Ál and found this was highly effective.

It has been our experience that two- or three-micrograms into the lateral ventricle is necessary to obtain a maximum cholinergic basal forebrain (CBF) lesion. However, these doses typically kill some cerebellar Purkinje cells. Another issue is that some cholinergic neurons in the NBM region are never killed by 192-Saporin.

Should we expect to be able to kill all or almost all ChAT SI neurons?

Mesulam's lab has some data [2,3] to suggest that these neurons innervate the amygdala and adjacent cortex. Generally lesions of the septum and diagonal band are complete, but when you get more caudal, i.e. SI region, there will be some cholinergic neurons left. When you do ChAT or AChE stains, the amygdala and adjacent cortex are not denervated whereas the hippocampus, olfactory system and all the rest of the cortex are devoid of cholinergic terminals.

Is there another toxin that will eliminate the remaining ChAT SI neurons?

There may be other targeted conjugates that could clean out the residual cells in the SI region if we knew what markers they co-express. For example, our SSP-saporin (Cat. #IT-11) conjugate is very good at removing cells that express the NK-1 receptor such as striatal cholinergic interneurons.

References

  1. Calza L, Giuliani A, Fernandez M, Pirondi S, D'Intino G, Aloe L, Giardino L (2003) Neural stem cells and cholinergic neurons: Regulation by immunolesion and treatment with mitogens, retinoic acid, and nerve growth factor. Proc Natl Acad Sci U S A 100(12):7325-7330.
  2. Heckers S, Mesulam M-M (1994) Two types of cholinergic projections to the rat amygdala. Neuroscience 60:383-397.
  3. Heckers S, Ohtake T, Wiley R, Lappi DA, Geula C, Mesulam M-M (1994) Complete and selective cholinergic denervation of rat neocortex and hippocampus but not amygdala by an immunotoxin against the p75 NGF receptor. J Neurosci 14:1271-1289.

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