Cholinergic neurotransmission in the central nervous system of the Snell dwarf mouse.
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.
Fuhrmann
G
G
Durkin
T
T
Thiriet
G
G
Kempf
E
E
Ebel
A
A
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000502:physiology*; D001923:Brain Chemistry; D002794:Choline / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002799:Cholinergic Fibers / Q000502:physiology*; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D011976:Receptors, Muscarinic / Q000032:analysis; D009435:Synaptic Transmission
D011976:Receptors, Muscarinic; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D002794:Choline