SEROTONERGIC NEUROTRANSMISSION IN THE SPINAL-CORD AND MOTOR CORTEX OFPATIENTS WITH MOTOR-NEURON DISEASE AND CONTROLS - QUANTITATIVE AUTORADIOGRAPHY FOR 5-HT1A AND 5-HT2 RECEPTORS
V. Forrest et al., SEROTONERGIC NEUROTRANSMISSION IN THE SPINAL-CORD AND MOTOR CORTEX OFPATIENTS WITH MOTOR-NEURON DISEASE AND CONTROLS - QUANTITATIVE AUTORADIOGRAPHY FOR 5-HT1A AND 5-HT2 RECEPTORS, Journal of the neurological sciences, 139, 1996, pp. 83-90
Serotonin 5-HT is a potent modulator of motor neuron excitability in t
he spinal cord. Serotonergic neurotransmission, because of its effects
on glutamatergic excitation, may be relevant to the pathogenesis and
therapy of motor neuron disease (MND). The human motor system was stud
ied at two levels, spinal cord and motor cortex, by autoradiography fo
r the 5-HT1A and 5-HT2 receptor subclasses. In addition, biochemical e
stimations of indole metabolites were performed in the spinal cord. Po
st mortem tissue from control cases and MND patients showed a reductio
n in 5-HT1A receptor binding in the cervical (p < 0.01) but not lumbar
ventral horn in MND. 5-HT2 receptors were preserved in the ventral ho
rn at both levels and were focally abundant around motor neuron somata
. Tissue levels of 5-HT were unchanged in the spinal cord in MND. The
metabolite 5-HIAA was increased in the cervical spinal cord in MND as
was the molar ratio of 5HIAA:5-HT, implying that there may be an incre
ased turnover of 5HT. In the motor cortex and premotor cortex the 5-HT
1A receptor remained unchanged in MND. There was a 20% reduction in 5-
HT2 receptor binding sites (p < 0.05) across all the cortical laminae
with preservation of the normal pattern of laminar binding. These chan
ges in two levels of the motor system in MND most likely represent phy
siological adaptations in the spinal cord and motor cortex rather than
primary involvement of the serotonergic system in the pathogenesis of
the disease.