Crassocephalum crepidioides extracts reverses the effects of valproic acid in an in-utero mouse model of autistic disorders

Irene Alice Folefack; Sefirin Djiogue; Jean G. Beppe; Nanou Gael Allah-Doum; Chiara N. Adjoffoin; Rudig Nikanor T. Djikem; Bertrand M. Barga; Perpetue M. Atsama; Woudamkine Sadou; Elisabeth Ngo Bum

doi:10.18203/2320-6012.ijrms20251274

Authors

Irene Alice Folefack Faculty of Science, University of Maroua, Maroua, Cameroon
Sefirin Djiogue Faculty of Science, University of Yaounde I, Yaounde, Cameroon
Jean G. Beppe Faculty of Science, University of Maroua, Maroua, Cameroon
Nanou Gael Allah-Doum Faculty of Science, University of Maroua, Maroua, Cameroon
Chiara N. Adjoffoin Faculty of Science, University of Yaounde I, Yaounde, Cameroon
Rudig Nikanor T. Djikem Faculty of Science, University of Yaounde I, Yaounde, Cameroon
Bertrand M. Barga Faculty of Science, University of Maroua, Maroua, Cameroon
Perpetue M. Atsama Faculty of Science, University of Yaounde I, Yaounde, Cameroon
Woudamkine Sadou Faculty of Science, University of Maroua, Maroua, Cameroon
Elisabeth Ngo Bum Faculty of Science, University of Maroua, Maroua, Cameroon

DOI:

https://doi.org/10.18203/2320-6012.ijrms20251274

Keywords:

Crassocephalum crepidioides, Social behaviour, Neuroprotection, Autism spectrum disorder, Valproic acid

Abstract

Background: Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by deficits in social communication and interaction, alongside restricted or repetitive behaviours. This study investigates the potential of hydroethanolic extract of Crassocephalum crepidioides (HEE) to ameliorate ASD-related behaviours in a valproic acid (VPA)-induced mouse model of in utero ASD. VPA exposure disrupts neurodevelopmental processes, affecting synaptic function and neural connectivity which are also seen in Autism.

Methods: Thirty pregnant female mice were used among which, six served as normal control group. the twenty-four remaining mice received valproic acid 600 mg/kg on gestational day 10 to day 12. Following parturition, offspring were treated daily from postnatal day 21 to 50. Behavioural assessments were conducted during the treatment period. Upon completion of behavioural testing, brains were collected for biochemical analysis of monoamine levels.

Results: Compared to the VPA-exposed control group, HEE treatment at all tested doses significantly reduced (p<0.001) the time spent investigating an empty chamber in a social preference test, and significantly increased (p<0.001) the time spent interacting with a social stimulus (sentinel). Furthermore, HEE treatment significantly increased (p<0.001) brain tissue concentrations of monoamines.

Conclusions: These findings suggest that Crassocephalum crepidioides extract may exert neuroprotective effects, improving both social behaviour and reducing repetitive behaviours in this VPA-induced mouse model of ASD. HEE has therapeutic potential by modulating neurotransmitter systems known to be disrupted in Autism.

Metrics

Metrics Loading ...

References

Sala R, Amet L, Blagojevic-Stokic N, Shattock P and Whiteley P. Bridging the gap between physical health and autism spectrum disorder. Neuropsychiatr Dis Treat. 2020;16:1605-18. DOI: https://doi.org/10.2147/NDT.S251394

CIM-10 Version. Disponible sur: Available at: http ://apps.Who.int/classifications/icd10/browse/2008/fr#/F84. Accessed on 17th March 2023.

Fombonne E. Epidemiology of pervasive developmental disorders. Pediatr Res. 2009;65(6):591- 8. DOI: https://doi.org/10.1203/PDR.0b013e31819e7203

Amiet C, Gourfinkel-An I, Bouzamondo A, Tordjman S, Baulac M, Lechat P, et al. Epilepsy in autism is associated with intellectual disability and gender: evidence from a meta-analysis. Biol Psychiatry. 2008;64:577–82. DOI: https://doi.org/10.1016/j.biopsych.2008.04.030

Poirier R, Jacquot S, Vaillend C, Soutthiphong AA, Libbey M, Davis S, et al. Deletion of the Coffin-Lowry syndrome gene Rsk2 in mice is associated with impaired spatial learning and reduced control of exploratory behavior. Behavior Genetics. 2007;37(1):31–50. DOI: https://doi.org/10.1007/s10519-006-9116-1

Nicolini C, Fahnestock M. Le modèle de rongeur induit par l'acide valproïque de l'autisme. Exp Neurol. 2018;299 (Pt A):217-27.

Ospina MB, Krebs SJ, Clark B, Karkhaneh M, Hartling L, Tjosvold L. Behavioural and developmental interventions for autism spectrum disorder : a clinical systematic review. PloS One. 2008;3(11):e 3755. DOI: https://doi.org/10.1371/journal.pone.0003755

McPheeters ML, Warren Z, Sathe N, Bruzek JL, Krishnaswami S, Jerome RN. A systematical review of medical treatments for children with autistic spectrum disorders. Pédiatrie, 2011;127(5):e1312–21. DOI: https://doi.org/10.1542/peds.2011-0427

Ernst E. Herb-drug interactions : potentially important but woefully under-researched. European Journal of Clinical Pharmacology. 2000;56(8):523-4. DOI: https://doi.org/10.1007/s002280000194

Noordin MY, Kim WC, Shahid I, Maznah I. Phenolic Content and Antioxidant Activity of Hibiscus cannabinus L, Seed Extracts after Sequential Solvent Extraction. Molecules. 2012;17(2012):12612-21. DOI: https://doi.org/10.3390/molecules171112612

Sandhya T, Sowjanya J, Veeresh B. Bacopa monniera (L.) Wettst ameliorates behavioral alterations and oxidative markers in sodium valproate induced autism in rats. Neurochemical Research. 2012;37(5):1121–31. DOI: https://doi.org/10.1007/s11064-012-0717-1

Samson G, Geoffroy G, Ouedraogo RL, Timofte D, Foyet HS, Hilou A, Kiendrebéogo M. Anxiolytic and anti-depressant effect of Salvia spp. essential oil on rat model of Autism Spectrum Disorder. Bulletin of Integrative Psychiatry. 2020;84. DOI: https://doi.org/10.36219/BPI.2020.1.02

Adjatin A, Dansi A, Badoussi E, Loko YL, Dansi M, Gbaguidi F, et al. Pphytochimical sceening and toxicity studies of Crassocephalum rubens and Crassocephalum crepidioides consumed as vegetable in Benin. Journal of Chemical and Pharmaceutical Research. 2013;6:160–7.

Sanjeev K. Activité anti inflammatoire, immunorégulateur et antigénotoxicité de l’extrait méthanolique de Crassocephalum crepidioides, 2018.

Adedayo BC, Ganiyu O, Sunday I, Oyeleye II, Ejakpovi AA, Boligon ML. Blanching alters the phenolic constituants and in vitro Antioxidant and anticholinesterase properties of fireweed Crassocephalum crepidioides, 2015. DOI: https://doi.org/10.1016/j.jtumed.2015.09.003

Benzie IFF, Strain JJ. The Ferric Reducing Ability of Plasma (FRAP) as a Measure of “Antioxidant Power” The FRAP Assay. Analytical Biochemistry. 1996;239(1):70–6. DOI: https://doi.org/10.1006/abio.1996.0292

Sun T, Tang J, Powers JR. Effect of Pectolytic Enzyme Preparations on the Phenolic Composition and Antioxidant Activity of Asparagus Juice. Journal of Agricultural and Food Chemistry. 2005;113:964-9. DOI: https://doi.org/10.1021/jf0491299

Ter Horst JP, van der Mark M, Kentrop J, Arp M, van der Veen R, De Kloet R, et al. Deletion of the forebrain mineralocorticoid receptor impairs social discrimination and decision-making in male, but not in female mice. Frontiers in Behavioral Neuroscience, 2014;8:26. DOI: https://doi.org/10.3389/fnbeh.2014.00026

Taiwe GS, Ngo Bum E, Dimo T, Weiss N, Moto FCO, Sidikki N, et al. Antidepressant, myorelaxant and anti-anxiety-like effects of Nauclea latifolia Smith (Rubiaceae) roots extract in murine models. J Pharmacol, 2010;6:364-71. DOI: https://doi.org/10.3923/ijp.2010.364.371

Wilbur KN, Bernheim F, Shapiro OW. Determination of lipid peroxidation. Archives of Biochemistry and Biophysics. 1949;24:305-10.

Mishra HP, Fridovich I. The role of superoxide anion in the autooxidation of epinephrine and a simple assay for superoxide dismutase. The journal of Biological Chemistry. 1972;247:1972-3170. DOI: https://doi.org/10.1016/S0021-9258(19)45228-9

Shina AK. Calorimetric assay of catalase, Analytical Biochemistry. 1972;47(2):389-94. DOI: https://doi.org/10.1016/0003-2697(72)90132-7

Robinson RG, SHoemaker WJ, Schlumpf MT, Bloom FE. Effect of experimental cerebral infarction in rat brain on catecholamine and behaviour. Nature. 1975;255(5506):332-4. DOI: https://doi.org/10.1038/255332a0

Laprade N, Soghomonian JJ. Glutamate decarboxylase (GAD65) gene expression is increased by dopamine receptor agonists in a subpopulation of rat striatal neurons. Mol Brain Research. 1997;48(2):333-45. DOI: https://doi.org/10.1016/S0169-328X(97)00112-5

Lowe IP, Robins E, Eyermen GS. The fluorimetric measurement of glutamic decarboxylase and its distribution in brain. J Neurochem. 1958;3(1):8-18. DOI: https://doi.org/10.1111/j.1471-4159.1958.tb12604.x

Cannet C. Artéfacts : les difficultés de la technique histologique de la circulation à la coupe. Rev Fr Histotechnol, 2006;19:71–84.

American Psychiatric Association, Diagnostic and statistical manual of mental disorders (5th ed.), 2013 ; Arlington, VA: auteur; 2013. DOI: https://doi.org/10.1176/appi.books.9780890425596

Kang J, Kim E. La suppression de la fonction des récepteurs NMDA chez les souris exposées avant la naissance à l'acide valproïque améliore les déficits sociaux et les comportements répétitifs. Front Mol Neurosci. 2015;;8:17.

Anderson G M: Development and neurobiology, Part 4: Serotonin in autism, Journal of the American Academy of Child & Adolescent Psychiatry. 2002;41:1513-6. DOI: https://doi.org/10.1097/00004583-200212000-00025

Murray F, Smith D W and Hutson P H: Chronic low dose corticosterone exposuredecreased hippocampal cell proliferation, volume and induced anxiety and depression like behaviours in mice. Eur J Pharmacol, 2008;583:115–27. DOI: https://doi.org/10.1016/j.ejphar.2008.01.014

Schneider T, Roman A, Basta-Kaim A, Kubera M, Budziszewska B, Schneider K and Przewłocki R : Gender-specific behavioral and immunological alterations in an animal model of autism induced by prenatal exposure to valproic acid. Psychoneuroendocrinology, 2008;33(6):728–40. DOI: https://doi.org/10.1016/j.psyneuen.2008.02.011

Bourin M, Hascoёt M. Implication of 5-HT2 receptor subtypes in the mechanism of action of the GABAergic compound etifoxine in the fourplate test in Swiss mice. Behavioural Brain Research. 2010;208:352-68. DOI: https://doi.org/10.1016/j.bbr.2009.11.046

Makkonen I, Riikonen R, Kokki H, Airaksinen MM, Kuikka JT. Serotonin and dopamine transporter binding in children with autism determined by SPECT. Dev Med Child Neurol. 2008;50:593-7. DOI: https://doi.org/10.1111/j.1469-8749.2008.03027.x

Lopes F, Ganzer L, Borges A, Kochenborger L, Januário C, Faria S, et al. Effects of GABA ligands injected into the nucleus accumbens shell on fear/anxiety-like and feeding behaviors in food-deprived rats. Pharm Biochem Behav, 2012;101:41-8. DOI: https://doi.org/10.1016/j.pbb.2011.11.013

Dringen R, Gutterer JM, Hirrlinger J. Glutathione metabolism in brain metabolic interaction between astrocytes and neurons in the defense against reactive oxygen species. Eur J Biochem. 2000;267:4912-6. DOI: https://doi.org/10.1046/j.1432-1327.2000.01597.x

Élizabeth B. Stress oxydatif cérébrovasculaire et rupture de la barrière hématoencéphalique dans le syndrome de Wernicke-Korsakoff expérimental. Thèse de Doctorat, Université de Montréal, 2010.

Boubekri C. Etude de l’activité antioxydante des polyphénols extraits de Solanum melongena par des techniques électrochimiques, Thèse Doctorat, Université de Biskra Algérie, 2014;56.

Alioune F, Ndiaye A, Hzounda F, Ndiefi FJ, Mbaye D, Mbacké DS et al. Phytochemical screening, polyphenol content and antioxidant studies of ethanol leaf extract of Combretum aculeatum Vent, European Journal of Medicinal Plants. 2015;10:1-7. DOI: https://doi.org/10.9734/EJMP/2015/20294

Luca M, Luca A, Calandra C. The Role of Oxidative Damage in the Pathogenesis and Progression of Alzheimer's Disease and Vascular Dementia. Oxid Med Cell Longev. 2015;504-678. DOI: https://doi.org/10.1155/2015/504678

Jie L, Wuliji O, Wei L, Zhi-Gang J, Hossein AG. Oxidative Stress and neurodegenerative Disorders. Int J Mol Sci. 2013;14(12):24438-75. DOI: https://doi.org/10.3390/ijms141224438

Garait B. Le stress oxydant induit par voie métabolique (régimes alimentaires) ou par voie gazeuse (hyperoxie) et effet de la GliSODin. (PhD thesis), Universite Joseph Fourier, grenoble, 2006;219p.

Sodhi MS, Sanders-Bush E. Serotonin and brain development. Int Rev Neurobiol. 2004;59:111-74. DOI: https://doi.org/10.1016/S0074-7742(04)59006-2

Vauzour, Rodriguez-Mateos A, Corova G, Oruna-Concha M, Spencer J. Polyphenols and human health: prevention of disease and mechanisms of action. Nutrients. 20102;1106-31. DOI: https://doi.org/10.3390/nu2111106