Substance P-containing neurons in the mesopontine tegmentum are severely affected in Parkinson's disease.
Substance P immunoreactive (SP+) neurons were analysed quantitatively in serial sections of the mesopontine tegmentum in 6 patients with idiopathic Parkinson's disease and 5 age-matched normal controls. In the tegmentum of the Parkinson's disease brains many SP+ neurons contained swollen, twisted neuronal processes as well as Lewy bodies. There were significant reductions in the total number of SP+ neurons in the pedunculopontine tegmental nucleus (loss 43%), in the laterodorsal tegmental nucleus (loss 28%), in the oral pontine reticular nucleus (loss 41%) and in the median raphe nucleus (loss 76%). It was the large SP+ (greater than 20 microns) neurons that were particularly affected. In our control group we did not document a significant relationship between age at death and number of SP+ neurons in these tegmental nuclei or between age at death and number of pigmented neurons in the locus coeruleus. In contrast, in patients with Parkinson's disease, there was a strong inverse relationship between age at death and numbers of SP+ and pigmented neurons. Our findings suggest an interaction between the pathophysiological mechanisms initiated by Parkinson's disease and other processes related to ageing. Since tegmental SP+ neurons are affected by the primary pathological processes underlying Parkinson's disease as severely as catecholamine-synthesizing neurons are affected, theories of pathogenesis and therapeutic strategies in Parkinson's disease will need to take into account the involvement of these SP+ neurons.
Gai
W P
WP
Department of Physiology, Flinders University of South Australia, Bedford Park.
Halliday
G M
GM
Blumbergs
P C
PC
Geffen
L B
LB
Blessing
W W
WW
D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000737:chemistry; D010300:Parkinson Disease / Q000378:metabolism*; D011149:Pons / Q000737:chemistry; D013373:Substance P / Q000032:analysis*; D013681:Tegmentum Mesencephali / Q000737:chemistry*
D013373:Substance P