Developmental expression of the neurotransmitter transporter NTT4

Neurotransmitter transporters are involved in termination of the synaptic neurotransmission and are implicated as the sites of action of antidepressant medicines and illicit drugs. In addition to their function in neurotransmission, neurotransmitter transporters play a key role in neuroregulation and brain development. In this report, the developmental distribution of the "orphan" transporter NTT4, whose substrate has not yet been shown, is described. Immunohistochemical studies have previously shown NTT4 to be specifically and widely localized to the central nervous system. In this report, the distribution of NTT4 in brain areas enriched in glutamatergic and gamma-aminobutyric acid-ergic innervations is further substantiated. NTT4 is detected beginning at E18 in various parts of the rat brain, including the cerebral cortex, fimbria hippocampi, fornix, lateral lemniscus, anterior commissure, and spinal cord. At E18, strong immunoreactivity of NTT4 is observed in the cortical subplate and marginal layers that later develops into the fimbria hippocampi, and at P22, the expression of NTT4 in the hippocampal formation reaches the mature form. The expression of NTT4 in the spinal cord begins at E18 in the ventral white matter. Heavy staining for NTT4 is observed in the substantia nigra since birth and through all time points examined. Transient immunoreactivity is observed in the inferior colliculus, reaching maximal expression at P10, whereas the superior colliculus commences to express NTT4 only after this time point. The globus pallidus is highly stained after birth, and the caudate putamen shows strong staining for NTT4 only at P22. In the adult rat brain, NTT4 is strongly expressed in the olfactory bulb, cerebral cortex, striatum, hippocampus, thalamus, substantia nigra, pontine nucleus, cerebellum, and spinal cord. The developmental distribution of NTT4 suggests involvement in central nervous system maturation.