Neuronal and Astroglial Response to Pre- and Perinatal Exposure to Delta-9-Tetra- Hydrocannabinol in the Rat Substantia nigra

Abstract

The responses of neurons and astroglial cells to pre- and perinatal exposure to Δ⁹-tetrahydrocannabinol (Δ⁹-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 Δ⁹-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 Δ⁹-THC decreased TH immunoreactivity in the SN of males on PD21 when compared to both their controls and Δ⁹-THC-exposed females of the same age. Furthermore, the TH expression decreased with age in Δ⁹-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 Δ⁹-THC-exposed females from PD21. These differences in neuronal development caused by prenatal Δ⁹-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 Δ⁹-THC-exposed male rats. Although GFAP expression increased in Δ⁹-THC-exposed males with age, it did not reach control levels by PD70. On the contrary, significantly increased GFAP expression in the Δ⁹-THC-exposed females on PD21 was observed, compared to their controls and also to Δ⁹-THC-exposed male rats; however, the GFAP expression shown by Δ⁹-THC-exposed females stabilized from PD21. These Δ⁹-THC-induced changes in the glial development could indicate that Δ⁹-THC accelerated the maturation of astrocytes in female rats, whereas Δ⁹-THC delayed astrocytic maturation in Δ⁹-THC-exposed males. These findings suggest that pre- and perinatal exposure to Δ⁹-THC can lead to long-term effects in both neurons and glial cells.