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. 2023 Nov;13(11):e3224.
doi: 10.1002/brb3.3224. Epub 2023 Aug 18.

Prangos ferulacea (L.) ameliorates behavioral alterations, hippocampal oxidative stress markers, and apoptotic deficits in a rat model of autism induced by valproic acid

Maryam Saadat  1 , Abbas Ali Taherian  1   2 , Mohammad Reza Aldaghi  3   1 , Payman Raise-Abdullahi  2 , Hamid Reza Sameni  3   1 , Abbas Ali Vafaei  2   4
Affiliations

Prangos ferulacea (L.) ameliorates behavioral alterations, hippocampal oxidative stress markers, and apoptotic deficits in a rat model of autism induced by valproic acid

Maryam Saadat et al. Brain Behav. 2023 Nov.

Abstract

Background: Prenatal exposure to valproic acid (VPA) may enhance the risk of autism spectrum disorder (ASD) in children. This study investigated the effect of Prangos ferulacea (L.) on behavioral alterations, hippocampal oxidative stress markers, and apoptotic deficits in a rat model of autism induced by valproic acid.

Methods: Pregnant rats received VPA (600 mg/kg, intraperitoneally [i.p.]) or saline on gestational day 12.5 (E 12.5). Starting from the 30th postnatal day (PND 30), the pups were i.p. administered Prangos ferulacea (PF, 100 and 200 mg/kg), or the vehicle, daily until PND 58. On PND 30 and 58, various behavioral tasks were used to evaluate pups, including the open field, elevated plus-maze, hot-plate, and rotarod test. On PND 65, the animals were euthanized, and their brains were removed for histopathological and biochemical assay.

Results: Prenatal exposure to VPA caused significant behavioral changes in the offspring, reversed by administering an extract of Prangos ferulacea (L.). Additionally, prenatal VPA administration resulted in increased levels of malondialdehyde and deficits in antioxidant enzyme activities in the hippocampus, including catalase and glutathione, ameliorated by PF. Likewise, postnatal treatment with PF improved VPA-induced dysregulation of Bax and Blc2 in the hippocampus and reduced neuronal death in CA1, CA3, and dentate gyrus.

Conclusion: The findings of this study suggest that postnatal administration of PF can prevent VPA-induced ASD-like behaviors by exhibiting antiapoptotic and antioxidant properties. Therefore, PF may have the potential as an adjunct in the management of ASD.

Keywords: Prangos ferulacea (L.); autism; hippocampus; oxidative stress; valproic acid.

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Conflict of interest statement

The authors declare no conflicts of interest. No financial gain was made during the research.

Figures

FIGURE 1
FIGURE 1
The time line of behavioral training, testing, and drug injections (see Section 2 for more details). GD: gestational day; PND: postnatal day; VPA: valproic acid.
FIGURE 2
FIGURE 2
The effects of Prangos ferulaceae (L.) on (a) anxiety‐like behaviors in the elevated plus maze (EPM), (b) motor balance in the rotarod (RT), (c) anxiety‐like behavior in the open field (OFT), and (d) pain responses in the hot plate (HPT) in offspring rats prenatally exposed to valproic acid (VPA) before and after treatment. Data are expressed as mean ± standard error of the mean (SEM): (a) p < .01 versus the control group, (b) p < .05 versus the PF100 group, (c) p < .01 versus the PF200 group, (d) p < .05 versus the VPA group. Control: healthy rats, PF100 and PF200: healthy rats received PF100 or PF200 (mg/kg), VPA: prenatally VPA‐exposed rats that received the vehicle, VPA+PF100 and VPA+PF200: prenatally VPA‐exposed rats that received PF100 or PF200 (mg/kg).
FIGURE 3
FIGURE 3
The effects of Prangos ferulaceae (L.) on hippocampal levels of (a) malondialdehyde (MDA), (b) catalase (CAT), and (c) glutathione (GSH) in a valproic acid (VPA)‐induced model of autism. Data are expressed as mean ± standard error of the mean (SEM): (a) p < .01 versus the control group, (b) p < .05 versus the VPA group, (c) p < .05 versus the VPA+PF100 group. Control: healthy rats, PF100 and PF200: Healthy rats received PF100 or PF200 (mg/kg), VPA: prenatally VPA‐exposed rats that received the vehicle, VPA+PF100 and VPA+PF200: prenatally VPA‐exposed rats that received PF100 or PF200 (mg/kg).
FIGURE 4
FIGURE 4
The effects of Prangos ferulaceae (L.) on the hippocampal protein levels of (a and b) Bax, (a and c) Bcl‐2, and (d) the Bax/Bcl‐2 ratio in a valproic acid (VPA)‐induced model of autism were analyzed through immunoblotting. Data are expressed as mean ± standard error of the mean (SEM): (a) p < .01 versus the control group, (b) p < .05 versus the PF100 group, (c) p < .01 versus the PF200 group. Control: healthy rats, PF100 and PF200: Healthy rats received PF100 or PF200 (mg/kg), VPA: prenatally VPA‐exposed rats that received the vehicle, VPA+PF100 and VPA+PF200: prenatally VPA‐exposed rats that received PF100 or PF200 (mg/kg).
FIGURE 5
FIGURE 5
The effects of Prangos ferulaceae (L.) on the percentage of neuronal death in the hippocampal CA1, CA3, and DG subregions in a valproic acid (VPA)‐induced model of autism. Data are expressed as mean ± standard error of the mean (SEM): (a) p < .001 versus the control group, (b) p < .01 versus the VPA group, (c) p < .05 versus the VPA+PF100 group. Control: healthy rats, PF100 and PF200: Healthy rats received PF100 or PF200 (mg/kg), VPA: prenatally VPA‐exposed rats that received the vehicle, VPA+PF100 and VPA+PF200: prenatally VPA‐exposed rats that received PF100 or PF200 (mg/kg), Nissl staining, (the scale bars are as follows: row 1 = 200 μm, row 2 = 100 μm, and row 3 = 20 μm, respectively).
FIGURE 5
FIGURE 5
The effects of Prangos ferulaceae (L.) on the percentage of neuronal death in the hippocampal CA1, CA3, and DG subregions in a valproic acid (VPA)‐induced model of autism. Data are expressed as mean ± standard error of the mean (SEM): (a) p < .001 versus the control group, (b) p < .01 versus the VPA group, (c) p < .05 versus the VPA+PF100 group. Control: healthy rats, PF100 and PF200: Healthy rats received PF100 or PF200 (mg/kg), VPA: prenatally VPA‐exposed rats that received the vehicle, VPA+PF100 and VPA+PF200: prenatally VPA‐exposed rats that received PF100 or PF200 (mg/kg), Nissl staining, (the scale bars are as follows: row 1 = 200 μm, row 2 = 100 μm, and row 3 = 20 μm, respectively).
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