Cocaine causes deficits in radial migration and alters the distribution of glutamate and GABA neurons in the developing rat cerebral cortex.

Cocaine causes deficits in radial migration and alters the distribution of glutamate and GABA neurons in the developing rat cerebral cortex.
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DOI:
10.1002/syn.20814
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发表时间:
2011-01
期刊:
影响因子:
2.3
通讯作者:
Freed, William J.
Freed, William J.
中科院分区:
医学4区
文献类型:
--
作者:
Lee, Chun-Ting;Chen, Jia;Worden, Lila T.;Freed, William J.

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出生前接触可卡因可引起胚胎新皮质细胞结构的改变,然而,参与这些改变的皮质神经元的生物学机制和类型尚不清楚。先前我们发现,可卡因抑制了新皮质脑室区(VZ)的神经前体细胞的增殖;在这里,我们研究了产前暴露于可卡因诱导的皮质神经发生和谷氨酸和GABA神经元迁移的变化。在新皮质神经发生的三个时期,妊娠大鼠每隔12小时两次腹腔注射20 mg/kg可卡因。通过对大脑皮层不同区域的Tuj1+、Glu+或GABA+细胞进行计数,观察新皮质面积和发育中神经元的分布。可卡因通过减小Tuj1+层的大小来减少新皮质面积,但仅在新皮质神经发生的早期给予可卡因。VZ内的谷氨酸能神经元数量增加,而皮质外板的数量减少。虽然新皮质和神经节隆起VZ的GABA+神经元数量没有变化,但其他所有新皮质板层的GABA+细胞数量都减少了。可卡因也破坏了GABA+细胞的切向迁移。这些发现表明,宫内暴露可卡因干扰了新皮质神经元的径向迁移,可能是由于促进了新皮质VZ前体细胞的分化,减少了对径向胶质细胞的引导支持。可卡因可阻断新皮质内谷氨酸和GABA能神经元的径向迁移,以及GABA能神经元从皮质下远脑区的切向迁移。这可能会导致新皮质细胞结构异常,并伴随着不良的功能影响。
Prenatal cocaine exposure induces cytoarchitectural changes in the embryonic neocortex; however, the biological mechanisms and type of cortical neurons involved in these changes are not known. Previously we found that neural progenitor proliferation in the neocortical ventricular zone (VZ) is inhibited by cocaine; here we examine the changes in cortical neurogenesis and migration of glutamate and GABA neurons induced by prenatal cocaine exposure. Pregnant rats received 20 mg/kg of cocaine intraperitoneally twice at an interval of 12 hr during three periods of neocortical neurogenesis. Neocortical area and distribution of developing neurons were examined by counting Tuj1+, glutamate+ or GABA+ cells in different areas of the cerebral cortex. Cocaine decreased neocortical area by reducing the size of the Tuj1+ layer, but only when administered during early periods of neocortical neurogenesis. The number of glutamatergic neurons was increased in the VZ, but was decreased in the outer cortical laminae. Although the number of GABA+ neurons in the VZ of both the neocortex and ganglionic eminences was unchanged, GABA+ cells decreased in all other neocortical laminae. Tangential migration of GABA+ cells was also disrupted by cocaine. These findings suggest that in utero cocaine exposure disturbs radial migration of neocortical neurons, possibly due to decreased radial glia guiding support through enhanced differentiation of neocortical VZ progenitors. Cocaine interrupts radial migration of both glutamatergic and GABAergic neurons within the neocortex, in addition to the tangential migration of GABAergic neurons from the subcortical telecephalon. This may result in abnormal neocortical cytoarchitecture and concomitant adverse functional effects.
DOI: 10.1016/j.ntt.2006.12.002
发表时间: 2007-05-01
影响因子: 2.9
作者:
Chiriboga, Claudia A.;Kuhn, Louise;Wasserman, Gail A.
通讯作者: Wasserman, Gail A.
DOI: 10.1111/j.1749-6632.1998.tb09725.x
发表时间: 1998-01-01
期刊: COCAINE: EFFECTS ON THE DEVELOPING BRAIN
影响因子: --
作者:
Frank, DA;Augustyn, M;Zuckerman, BS
通讯作者: Zuckerman, BS
DOI: 10.1037/0012-1649.34.3.565
发表时间: 1998-05-01
影响因子: 4
作者:
Alessandri, SM;Bendersky, M;Lewis, M
通讯作者: Lewis, M
DOI: 10.1016/0006-8993(92)90450-n
发表时间: 1992-02-14
期刊: BRAIN RESEARCH
影响因子: 2.9
作者:
AKBARI, HM;KRAMER, HK;AZMITIA, EC
通讯作者: AZMITIA, EC
DOI: 10.1093/jpepsy/jsj027
发表时间: 2006-01-01
影响因子: 3.6
作者:
Behnke, M;Eyler, FD;Wobie, K
通讯作者: Wobie, K