Suárez I, Bodega G, Ramos J A, Fernández-Ruiz J J, Fernández B
Departamento de Biología Celular y Genética, Universidad de Alcalá, Madrid, España.
Dev Neurosci. 2000;22(4):253-63. doi: 10.1159/000017449.
The responses of neurons and astroglial cells to pre- and perinatal exposure to Delta(9)-tetrahydrocannabinol (Delta(9)-THC) were evaluated in the substantia nigra (SN) of male and female rats, at three postnatal ages (PD21, PD30 and PD70), by immunohistochemical detection of tyrosine hydroxylase (TH) in dopaminergic neurons and of glial fibrillary acidic protein (GFAP) in astrocytes. Our results showed that the effects of pre- and perinatal exposure to Delta(9)-THC on neuronal and astroglial immunoreactivities in the SN (compacta and reticulata) varied with sex, with male rats being more susceptible than females. Prenatal exposure to Delta(9)-THC decreased TH immunoreactivity in the SN of males on PD21 when compared to both their controls and Delta(9)-THC-exposed females of the same age. Furthermore, the TH expression decreased with age in Delta(9)-THC-exposed males in the SNc pars compacta, whereas it increased in controls. On the contrary, TH expression was maintained stable in the SN pars compacta of Delta(9)-THC-exposed females from PD21. These differences in neuronal development caused by prenatal Delta(9)-THC exposure were associated with significant differences in GFAP expression by astroglial cells in both sexes. On PD21, GFAP immunoreactivity decreased in the SN in Delta(9)-THC-exposed male rats. Although GFAP expression increased in Delta(9)-THC-exposed males with age, it did not reach control levels by PD70. On the contrary, significantly increased GFAP expression in the Delta(9)-THC-exposed females on PD21 was observed, compared to their controls and also to Delta(9)-THC-exposed male rats; however, the GFAP expression shown by Delta(9)-THC-exposed females stabilized from PD21. These Delta(9)-THC-induced changes in the glial development could indicate that Delta(9)-THC accelerated the maturation of astrocytes in female rats, whereas Delta(9)-THC delayed astrocytic maturation in Delta(9)-THC-exposed males. These findings suggest that pre- and perinatal exposure to Delta(9)-THC can lead to long-term effects in both neurons and glial cells.
通过免疫组织化学检测多巴胺能神经元中的酪氨酸羟化酶（TH）和星形胶质细胞中的胶质纤维酸性蛋白（GFAP），评估了雄性和雌性大鼠在出生前和围产期暴露于Δ⁹-四氢大麻酚（Δ⁹-THC）后，在三个出生后年龄（出生后第21天、第30天和第70天）黑质（SN）中的神经元和星形胶质细胞的反应。我们的结果表明，出生前和围产期暴露于Δ⁹-THC对SN（致密部和网状部）中神经元和星形胶质细胞免疫反应性的影响因性别而异，雄性大鼠比雌性更易受影响。与对照组和同年龄的Δ⁹-THC暴露雌性大鼠相比，出生前暴露于Δ⁹-THC使出生后第21天雄性大鼠SN中的TH免疫反应性降低。此外，在黑质致密部中，暴露于Δ⁹-THC的雄性大鼠的TH表达随年龄下降，而对照组则升高。相反，从出生后第21天起，暴露于Δ⁹-THC的雌性大鼠黑质致密部中的TH表达保持稳定。出生前暴露于Δ⁹-THC引起的神经元发育差异与两性星形胶质细胞中GFAP表达的显著差异有关。在出生后第21天，暴露于Δ⁹-THC的雄性大鼠SN中的GFAP免疫反应性降低。尽管暴露于Δ⁹-THC的雄性大鼠中GFAP表达随年龄增加，但到出生后第70天仍未达到对照水平。相反，与对照组以及暴露于Δ⁹-THC的雄性大鼠相比，观察到出生后第21天暴露于Δ⁹-THC的雌性大鼠中GFAP表达显著增加；然而，暴露于Δ⁹-THC的雌性大鼠中GFAP表达从出生后第21天起稳定下来。这些由Δ⁹-THC诱导的神经胶质发育变化可能表明，Δ⁹-THC加速了雌性大鼠星形胶质细胞的成熟，而Δ⁹-THC延迟了暴露于Δ⁹-THC的雄性大鼠星形胶质细胞的成熟。这些发现表明，出生前和围产期暴露于Δ⁹-THC可对神经元和神经胶质细胞产生长期影响。
