Cholinergic neurotransmission in the central nervous system of the snell dwarf mouse

Abstract

An unequal decrease in cholinergic activity has been evidenced in discrete brain areas in the growth hormone, thyroid-stimulating hormone and prolactin deficient Snell dwarf mouse. The effect of the mutation's pituitary deficit on central cholinergic mechanisms appears to be selective: Normally high cholinergic activity areas such as striatum, olfactory tubercles, and hippocampus show strong alterations in this neurotransmitter system. Structures which appear earlier in ontogenesis are less affected, if at all. The lack of pituitary hormones seems to have effects on choline acetyltransferase activity and/or synthesis as well as on the development of high affinity (H.A.) cholinergic uptake mechanisms, both strongly defective in hippocampus and striatum. Therefore, a lower density of cholinergic terminals can be inferred. Furthermore, our observations are consistent with a close functional coupling of the choline H.A. transport and of subsequent choline acetylation. Acetylcholinesterase activity does not seem to be affected. Moreover, a compensatory effect at the postsynaptic level may have occurred due to developmental or functional plasticity for cholinergic responsiveness. In conclusion, the dwarf mouse seems to be a useful model for a better understanding of the influences of growth hormone and thyroid hormones on the development of central cholinergic mechanisms. It also provides the possibility to attempt a functional restoration of the deficient cholinergic neurotransmission and the behavioral disturbances which may be linked to them, by hormone replacement.

PET imaging of cholinergic deficits in rats using [18F]fluoroethoxybenzovesamicol ([18F]FEOBV)

“…This distribution pattern is in agreement with published values for concentrations of VAChT, known to be associated with cholinergic terminals (Gilmor et al, 1996;Ichikawa et al, 1997;Weihe et al, 1996). That distribution pattern is also consistent with the one found in other immunohistochemistry studies targeting presynaptic cholinergic markers such as ChAT and VAChT (Fuhrmann et al, 1985), as well as with previous PET imaging studies with [ 18 F] FEOBV (Landry St-Pierre et al, 2008a;Mulholland et al, 1998). The time-activity profiles of cortical and striatal uptakes are also mostly concordant with those reported by Kilbourn et al (2009), with the exception of a lower uptake toward the end of the scanning period, possibly explained by the different rat strain used.…”

Cholinergic Depletion in Alzheimer’s Disease Shown by [18F]FEOBV Autoradiography

“…In terms of ROI distribution, the relative concentrations of [ 18 F]FEOBV binding in the cortex and hippocampus match those found in postmortem studies using cholinergic markers both in humans [32, 33] and rodents [34]. Interestingly, the variance of [ 18 F]FEOBV binding is much lower in the AD tissues than in controls both for the PFC and hippocampal ROIs.…”

Postnatal growth hormone deficiency in growing rats causes marked decline in the activity of spinal cord acetylcholinesterase but not butyrylcholinesterase

“…Lastly they found that while ChAT was marked affected by GH deficiency, AChE was less affected whereas we found marked and significant declines in the AChE activity of the SC. Notwithstanding the differences between the study of Fuhrmann et al (1985) and ours, both clearly suggest that GH plays an important role in the postnatal development of the CNS cholinergic system.…”