Early glutathione intervention educed positive correlation between VGLUT1 expression and spatial memory in the Nω-nitro-L-arginine methyl rat model of IUGR

Philemon D Shallie; Adedeji I Sulaiman; Motunrayo K Oladejo; Oluwadamilola F Shallie; Thajasvarie Naicker

doi:10.1016/j.ibneur.2021.02.003

Early glutathione intervention educed positive correlation between VGLUT1 expression and spatial memory in the Nω-nitro-L-arginine methyl rat model of IUGR

IBRO Neurosci Rep. 2021 Feb 9:10:136-141. doi: 10.1016/j.ibneur.2021.02.003. eCollection 2021 Jun.

Authors

Philemon D Shallie¹, Adedeji I Sulaiman¹, Motunrayo K Oladejo¹, Oluwadamilola F Shallie², Thajasvarie Naicker³

Affiliations

¹ Department of Anatomy, Olabisi Onabanjo University, Ago-Iwoye, Nigeria.
² Discipline of Physiological Sciences, University of KwaZulu-Natal., Durban, South Africa.
³ Optics and Imaging Centre, University of KwaZulu-Natal., Durban, South Africa.

Abstract

Introduction: One of the most compelling causes of perinatal mortality and morbidity is intrauterine growth restriction (IUGR). IUGR is linked with numerous health challenges that last lifelong, including neurodevelopmental impairment and a high incidence of brain dysfunction. There is mounting evidence that places the glutamatergic system at the center of the neurobiology and treatment of neurological diseases. Therefore, this study investigated the effects of postnatal glutathione intervention on the spatial memory and the expressions of vesicular glutamate transporter 1 (VGLUT1) in the hippocampus and the cerebellar cortex of Nω-nitro-L-arginine methyl (L-NAME)-induced rat model of IUGR.

Materials and method: Twelve adult female rats were divided into Control and L-NAME groups; each containing 6 female rats. The control group received a single daily dose of normal saline while the L-NAME group was administered 50 mg/kg L-NAME daily from gestational day 9 until parturition. Offspring of the control rats were given free access to feeds while offspring from the L-NAME group were assigned into 3 groups: G1: given free access to feeds; G2 and G3 were administered 1.5 mg/kg body weight of glutathione from postnatal day (PND) 4-9 and PND 25-31 respectively. At the end of the intervention, Y-maze was conducted, and the rats euthanized on PND 35. The brain sections were processed, and immunofluorescence staining was performed using the Vectafluor Excel R.T.U Antibody kit.

Results: IUGR caused a significant 31.1% decrease in spontaneous alternation percentage (SAP), while early treatment with glutathione at PND 4-9 significantly (p < 0.01) increased SAP, while late treatment at PND 25-9 significantly decreased SAP compared to IUGR group. Furthermore, IUGR caused significant (p < 0.001) downregulation in corrected total cell fluorescence (CTCF) of VGLUT1 in both the hippocampus and cerebellar cortex. While treatment with glutathione caused upregulation in CTCF of VGLUT1 in the hippocampus and the cerebellar cortex.

Conclusion: Our results showed that early intervention with glutathione has significant therapeutic potential via upregulation of VGLUT1 expression in both hippocampus and cerebellar cortex, which positively correlated with enhanced spatial memory in IUGR rat model.

Keywords: Cerebellar cortex; Glutathione; Hippocampus; IUGR; L-NAME; VGLUT1.