Serotonergic neurotransmission in the spinal cord and motor cortex of patients with motor neuron disease and controls: quantitative autoradiography for 5-HT 1a and 5-HT 2 receptors

Abstract

Serotonin 5-HT is a potent modulator of motor neuron excitability in the 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 studied at two levels, spinal cord and motor cortex, by autoradiography for the 5-HT 1A and 5-HT 2 receptor subclasses. In addition, biochemical estimations of indole metabolites were performed in the spinal cord. Post mortem tissue from control cases and MND patients showed a reduction in 5-HT 1A receptor binding in the cervical ( p < 0.01) but not lumbar ventral horn in MND. 5-HT 2 receptors were preserved in the ventral horn 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 increased 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-HT 2 receptor binding sites ( p < 0.05) across all the cortical laminae with preservation of the normal pattern of laminar binding. These changes in two levels of the motor system in MND most likely represent physiological adaptations in the spinal cord and motor cortex rather than primary involvement of the serotonergic system in the pathogenesis of the disease.