Ljubic-Thibal V, Morin A, Diksic M, Hamel E
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, QC, Canada.
Synapse. 1999 Jun 1;32(3):177-86. doi: 10.1002/(SICI)1098-2396(19990601)32:3<177::AID-SYN4>3.0.CO;2-D.
The regulation of serotonin synthesis was investigated in the serotonergic neurons, which provide afferents to the dorsolateral hypothalamus (DLH). The origin of the DLH projection neurons within the raphe nucleus was identified by retrograde transport of Cholera toxin (CTb) and their serotonergic nature confirmed by tryptophan hydroxylase (TPH) immunocytochemistry. Disruption of serotonin synthesis steady-state was induced unilaterally by a selective and local destruction of serotonergic nerve terminals with 5,7-dihydroxytryptamine (5,7-DHT), stereotaxically injected in the right DLH. The results show that most of the serotonergic dorsal raphe neurons projecting to the DLH have an ipsilateral localization within the lateral aspects of the nucleus. In rats with unilateral DLH lesion, a population of serotonergic cells within the raphe nucleus exhibited a clear increase in TPH mRNA. These cells were about five times more numerous in the ipsilateral as compared to the contralateral dorsal raphe nucleus and they had, for the most part, a lateral localization within the raphe nucleus. Sham-operated rats did not exhibit any upregulation of TPH mRNA. Together, the present results provide the first demonstration that a discreet and selective destruction of serotonergic terminals induces a circumscribed and striking increase in TPH mRNA expression in a subset of brainstem serotonergic neurons projecting to and/or passing through the DLH. On the basis of these results and previous in vivo measurements of TPH activity (e.g., 5-HT synthesis), we suggest that this upregulation in TPH mRNA expression results from the loss of pre-synaptic and/or post-synaptic regulation of serotonin synthesis. These new findings raise important issues related to the repercussions of a local disruption in serotonergic neurotransmission on brain areas remote from the site of injury.
研究了向背外侧下丘脑（DLH）提供传入神经的5-羟色胺能神经元中5-羟色胺合成的调节。通过霍乱毒素（CTb）的逆行转运确定了中缝核内DLH投射神经元的起源，并通过色氨酸羟化酶（TPH）免疫细胞化学证实了它们的5-羟色胺能性质。通过立体定位注射到右侧DLH中的5,7-二羟基色胺（5,7-DHT）选择性地局部破坏5-羟色胺能神经末梢，单侧诱导5-羟色胺合成稳态的破坏。结果表明，大多数投射到DLH的5-羟色胺能背侧中缝神经元在核的外侧具有同侧定位。在单侧DLH损伤的大鼠中，中缝核内的一群5-羟色胺能细胞表现出TPH mRNA明显增加。与对侧背侧中缝核相比，同侧这些细胞的数量大约多五倍，并且它们在中缝核内大部分位于外侧。假手术大鼠未表现出TPH mRNA的任何上调。总之，目前的结果首次证明，5-羟色胺能末梢的离散和选择性破坏会导致投射到和/或穿过DLH的脑干5-羟色胺能神经元亚群中TPH mRNA表达出现局限性且显著增加。基于这些结果和先前对TPH活性的体内测量（例如5-羟色胺合成），我们认为TPH mRNA表达的这种上调是由于5-羟色胺合成的突触前和/或突触后调节丧失所致。这些新发现提出了与5-羟色胺能神经传递局部破坏对远离损伤部位的脑区的影响相关的重要问题。
