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大鼠出生后发育过程中脑儿茶酚胺能神经元的神经化学特征

Neurochemical characteristics of cerebral catecholamine neurons during the postnatal development in the rat.

作者信息

Hedner T, Lundborg P

出版信息

Med Biol. 1981 Aug;59(4):212-23.

PMID:6803074
Abstract

The development of cerebral dopamine (DA) and noradrenaline (NA) neurons was studied biochemically in 1- to 28-day-old rats. The precursor amino acid tyrosine increased to a steady state level in the whole brain during early postnatal age. After 14 days, however, there was a marked drop in the brain tyrosine level. In general, regional tyrosine levels also decreased between 4 and 28 days. DOPA accumulation was measured in whole brain and regional brain areas after inhibition of L-aromatic amino acid decarboxylase with NSD 1015. This is a well recognized method for estimating the in vivo rate of tyrosine hydroxylase activity. Whole brain DOPA accumulation after NSD 1015 increased progressively during postnatal life, and between 1 and 28 days a more than 3-fold increase was noted. Similar increases were also found in whole brain DA and NA levels during the corresponding period. Regional DA and NA levels generally increased with advancing age, with the highest DA levels in the striatum region and NA levels in the midbrain region. Regional DOPA accumulation after NSD 1015, reflecting in vivo tyrosine hydroxylase activity, increased in a similar fashion as the endogenous neurotransmitter levels. Measurements of DA and NA disappearance after alpha-methyltyrosine indicated the existence of an adult-like nerve impulse activity in DA neurons in the striatum and midbrain regions and in NA neurons in the hemispheres region of the 4-day-old rats. Gammahydroxybutyric acid (GHBA), which causes an inhibition of nerve impulse activity, was given to 4- and 28-day-old rats. This induced an initial increase in CA synthesis as measured by the NSD 1015 method at both ages. The results from this investigation show that the age-related regional increases in endogenous DA and NA levels closely follow the increase in regional tyrosine hydroxylase activity measured in vivo. Furthermore, the study also supports the view that feed-back mechanisms, resulting in an increased transmitter synthesis, exist in DA neurons after nerve impulse inhibition by GHBA at an early postnatal age.

摘要

采用生化方法研究了1至28日龄大鼠脑内多巴胺(DA)和去甲肾上腺素(NA)神经元的发育情况。出生后早期,全脑中的前体氨基酸酪氨酸增加至稳态水平。然而,14天后,脑内酪氨酸水平显著下降。总体而言,4至28天期间各区域的酪氨酸水平也有所降低。用NSD 1015抑制L-芳香族氨基酸脱羧酶后,测定全脑和脑区的多巴积累量。这是一种公认的估算酪氨酸羟化酶体内活性速率的方法。NSD 1015处理后,全脑多巴积累量在出生后逐渐增加,1至28天内增加了3倍多。同期全脑DA和NA水平也有类似增加。各区域DA和NA水平一般随年龄增长而升高,纹状体区域DA水平最高,中脑区域NA水平最高。NSD 1015处理后各区域的多巴积累量反映了体内酪氨酸羟化酶活性,其增加方式与内源性神经递质水平相似。α-甲基酪氨酸处理后对DA和NA消失情况的测量表明,4日龄大鼠的纹状体和中脑区域的DA神经元以及半球区域的NA神经元中存在类似成年动物的神经冲动活动。向4日龄和28日龄大鼠注射γ-羟基丁酸(GHBA),它会抑制神经冲动活动。这在两个年龄段均通过NSD 1015法测定诱导了儿茶酚胺合成的初始增加。本研究结果表明,内源性DA和NA水平与年龄相关的区域增加密切跟随体内测量的区域酪氨酸羟化酶活性的增加。此外,该研究还支持这样一种观点,即在出生后早期,GHBA抑制神经冲动后,DA神经元中存在导致递质合成增加的反馈机制。

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