The potential neuroprotective effects of Spirulina platensis in a valproic acid-induced experimental model of autism in the siblings of albino rats: targeting PIk3/AKT/mTOR signalling pathway

ABSTRACT

Introduction: Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders with poor social interaction, communication issues, aberrant motor movements, and limited repetitive interests and behaviour. Spirulina platensis (SP) contains several multi-nutrients and has a wide range of neuroprotective properties.

Aim: The target of the current experiment is to detect the protective effects of S. platensis on valproic-induced autism in adult female albino rats’ siblings for the first time.

Materials and Methods: Twelve Pregnant rats were separated into four main groups; Group I (control); Group II (S. platensis); Group III (autistic group); and Group IV (autistic SP-treated group). Fifteen offspring pups from each group were sacrificed, brain was divided for biochemical analysis as superoxide dismutase and malondialdehyde were evaluated spectrophotometrically while interleukin-6, interleukin-12, Bcl-2-associated X protein, B-cell lymphoma-2, Beclin-1, brain-derived neurotrophic factor were assessed by ELISA, other division of brain were used for gene expression of PI3k, Akt and mTOR pathway, last division of brain were stained using (H&E) and Giemsa stains. Tumour necrosis factor alpha (TNF-$\alpha )$ and Synaptophysin (SYN) markers were used for immunohistochemical staining.

Results: Autistic Group (III) showed an increment in levels of MDA, IL-6, IL12 and BAX while showing a decrement in SOD, Bcl-2 and Beclin-1 as well as increased PI3k, Akt and mTOR gene expression. Autistic Group (III) also exhibited hypocellularity and disorganization of hippocampal and prefrontal cortex cells. The autistic SP-treated group (IV) showed improvement in these biochemical markers and pathological changes. Our findings suggest that Spirulina platensis will be significant in managing autism.

KEYWORDS:

• Hippocampus
• prefrontal cortex
• Bcl-2-associated X protein
• brain-derived neurotrophic factor
• synaptophysin

Acknowledgements

Conceptualization, R I, A R A, and W A N; Methodology and Formal analysis, R I, A R A, W A N, A O, S M, E H B and H A I; investigation, F H R, A F E, NGMA and A E; Funding acquisition, N.A. and NGMA. Writing- original draft preparation, R I, A R A, W A N, E H B, NA, and H A I; writing-review and editing, R I, A R A, W A N, F H R, A F E, A O and S M; supervision, R I. All authors have read and approved the final manuscript. Animals used in these experiments were treated in accordance with the procedures approved by the ethical committee of Tanta University (Approval Code Number: 35867/9/22), approval date: 9/2022. NO human blood sample was included.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The authors confirm that the data supporting this study are available within the article [and/or] its supplementary materials.

Additional information

Funding

The authors extend their appreciation to Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2024R89), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia for funding this work.

Notes on contributors

Radwa Ismail

Radwa Ismail is lecturer of Anatomy and Embryology Department, faculty of medicine Tanta university, Egypt. PhD in anatomy and embryology, 13 years' experience in teaching, Medical neuroscience online course from brain research center- Duke university, and has a certain interest in neuroscience research and 3D slicer platform brain volumetric analysis.

Walaa A. Negm

Walaa A. Negm Assistant professor of Pharmacognosy Faculty of Pharmacy Tanta University. Winner of the Tanta University Encouragement Award in the field of Medical Sciences for the academic year 2022/2023. She has more than 85 scientific papers in the field of pharmaceutical and medical sciences in many prestigious international journals especially in natural products and phytochemistry fields.

Eman H. Basha

Eman H. Basha is lecturer of physiology at physiology department, faculty of medicine Tanta university, Egypt. PhD in physiology and has a certain interest in neuroscience and endocrinal research.

Fatma H. Rizk

Fatma H. Rizk is an assistant professor of physiology at the Faculty of Medicine, Tanta University, Egypt, and interested in neuroscience.

Nashwah G. M. Attallah

Nashwah G. M. Attallah Associate professor of pharmaceuticals chemistry in Egyptian Drug Authority. Interested in research in field of synthesis of new molecules with expected pharmacological effects as well as isolation and identification of different chemical compounds and analysis of chemical compounds using recent analysis techniques.

Najla Altwaijry

Najla Altwaijry Associate professor, Pharmaceutical Sciences Department, Princess Nourah bint Abdulrahman University. B.Pharm from King Saud University. Msc degree in Pharmaceutical Analysis. Ph.D in Pharmaceutical Sciences – Strathclyde Institute of Pharmacy and Biomedical Sciences (SIPBS) – University of Strathclyde, Glasgow, Scotland. Postgraduate Certificate in Researcher Professional Development –- University of Strathclyde, Glasgow, Scotland Leadership Training Program – INSEAD Business School, Fontainebleau, France. Research interests in drug discovery and development of anticancer drugs.

Hoda Ali Ibrahim

Hoda Ali Ibrahim is an assistant professor of medical biochemistry and molecular biology, Faculty of Medicine, Tanta University, Egypt.

Asmaa Fawzy Eltantawy

Asmaa Fawzy Eltantawy is a lecturer of Medical Pharmacology at Medical Pharmacology department, Faculty of Medicine, Tanta university, Egypt, and interested in gene therapy and neurological disorders.

Alaa Elkordy

Alaa Elkordy is lecturer of neuropsychiatry at Neuropsychiatry department, faculty of medicine, Tanta university, Egypt, and has a certain interest in neuroscience and stroke research.

Aya Osama

Aya Osama a senior researcher in the proteomics and metabolomics unit at the Children's Cancer Hospital in Egypt, specializes in proteomics, metaproteomics, metabolomics, and molecular biology. Her research interests include proteomics, the microbiome, and molecular biology. Among her notable publications are Integrated Multiomics Analysis to Infer COVID-19 Biological Insights and UniprotR: Retrieving and Visualizing Protein Sequence and Functional Information from Universal Protein Resource (UniProt Knowledgebase).

Sameh Magdeldin

Sameh Magdeldin Head of proteomics and metabolomics unit at the Children's Cancer Hospital in Egypt, specializes in proteomics, Mass spectrometry and metabolomics. His research interests include proteomics, metaproteomics, and metabolomics. Among his notable publications are Detection of early prognostic biomarkers for metastasis of Ewing's sarcoma in pediatric patients and UniprotR: Retrieving and Visualizing Protein Sequence and Functional Information from Universal Protein Resource (UniProt Knowledgebase).

Asmaa Ramadan Azzam

Asmaa Ramadan Azzam is a lecturer of Anatomy and Embryology Department, ffaculty of medicine Tanta university, Egypt. PhD in anatomy and embryology, 14 years' experience in teaching and has a certain interest in neuroscience research.