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Fulltext Antidepressant-Like Properties of Fish Oil on Postpartum Depression-Like Rats Model: Involvement of Serotonergic System

Abdul Aziz NU, Chiroma SM, Mohd Moklas MA, Adenan MI, Ismail A, Hidayat Baharuldin MT

Brain Sci, 2020 Oct 13;10(10).
PMID: 33066310 DOI: 10.3390/brainsci10100733

Pathophysiology of postpartum depression (PPD) has been associated with many factors, such as neuroendocrine, neuroinflammation and neurotransmitter changes. Fish oil (FO) improves PPD both in humans and animals. However, little is known with regards to its pharmacology on a PPD-like rat model. Hence, the current study aimed at investigating the effects of FO on a PPD-like rat model. Female rats were induced with PPD-like symptoms and then randomly divided into six groups (n = 6) for two experimental protocols. Protocol 1 consisted of PPD-like rats (2 mL distilled water), PPD-like + FO (9 g/kg/d) and PPD-like + Fluoxetine (FLX) (15 mg/kg/d) groups of rats, whereas Protocol 2 consisted of PPD-like rats (2 mL distilled water) + PCPA (p-chlorophenylalanine) 150 mg/kg, PPD-like + FO (9 g/kg/d) + PCPA 150 mg/kg and PPD-like + FLX (15 mg/d) + PCPA 150 mg/kg groups of rats, respectively. All treatments were administered orally for 10 days postpartum, except PCPA, which was given intraperitoneally. Prior to euthanasia, the antidepressant-like effect of the FO was evaluated using the forced swimming test (FST) and open field test (OFT) on day 10 postpartum. Biochemical analysis of serotonin, serotonin metabolite and serotonin turnover from their prefrontal cortex and hippocampus were also measured. The results showed that FO decreased immobility time and increased swimming time significantly, but not climbing time in FST. Further, it also decreased serotonin metabolite and turnover significantly in the hippocampus of the PPD-like rats. In contrast, administration with PCPA reversed all the outcomes. The antidepressant-like effects of FO were found to be similar with that of FLX. Thus, it can be concluded that FO exerts its antidepressant-like effects in PPD-like rats through modulation of serotonergic system.
Fulltext Effect of Resistance Training Methods and Intensity on the Adolescent Swimmer's Performance: A Systematic Review

Guo W, Soh KG, Zakaria NS, Hidayat Baharuldin MT, Gao Y

Front Public Health, 2022;10:840490.
PMID: 35444975 DOI: 10.3389/fpubh.2022.840490

BACKGROUND: Resistance training has been widely used in various sports and improves competition performance, especially in swimming. Swimming performance is highly dependent on muscle strength, especially short distances. For adolescent athletes, the existing literature has bound to prove that resistance training is undoubtedly bound to improve swimmers' performance.
OBJECTIVES: This study adopts a systematic literature review to (1) examine the effects of resistance training on the performance of adolescent swimmers, and (2) summarize their training methods and intensity.
METHODS: The literature search was undertaken in five international databases: the SCOUPS, PubMed, EBSCOhost (SPORTDiscus), CNKL, Web of Science. The searches covered documents in English and Chinese published until 30th December 2020. Electronic databases using various keywords related to "strength training" and "adolescent swimmers" were searched. Sixteen studies met the inclusion and exclusion criteria where the data was then systematically reviewed using the PRISMA guideline. Furthermore, the physical therapy evidence database (PEDro) scale was used to measure each study's scientific rigor.
RESULTS: This review found that to improve the swimming performance of adolescents, two types of resistance training were used, specifically in water and on land, where both types of training can improve swimming performance. In addition, training with two types of resistance machines were better in the water than with one equipment. Resistance training can improve the swimming performance of adolescent swimmers at 50 m, 100 m, 200 m and 400 m distances. However, most studies only focused on the swimming performance at 50 m and 100 m lengths. A low-intensity, high-speed resistance training programme is recommended for adolescent swimmers to obtain the best training results.
CONCLUSION: Water or land resistance training can improve the swimming performance. Given that both types of exercises have their strengths and weaknesses, combining these methods may enhance the swimmers' performance. In addition, despite the starting and turning phases consuming up to one-third of the total swimming time for short distances, literature in this area is limited.
SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero, identifier: CRD42021231510.
Fulltext Establishing Natural Nootropics: Recent Molecular Enhancement Influenced by Natural Nootropic

Suliman NA, Mat Taib CN, Mohd Moklas MA, Adenan MI, Hidayat Baharuldin MT, Basir R

Evid Based Complement Alternat Med, 2016;2016:4391375.
PMID: 27656235 DOI: 10.1155/2016/4391375

Nootropics or smart drugs are well-known compounds or supplements that enhance the cognitive performance. They work by increasing the mental function such as memory, creativity, motivation, and attention. Recent researches were focused on establishing a new potential nootropic derived from synthetic and natural products. The influence of nootropic in the brain has been studied widely. The nootropic affects the brain performances through number of mechanisms or pathways, for example, dopaminergic pathway. Previous researches have reported the influence of nootropics on treating memory disorders, such as Alzheimer's, Parkinson's, and Huntington's diseases. Those disorders are observed to impair the same pathways of the nootropics. Thus, recent established nootropics are designed sensitively and effectively towards the pathways. Natural nootropics such as Ginkgo biloba have been widely studied to support the beneficial effects of the compounds. Present review is concentrated on the main pathways, namely, dopaminergic and cholinergic system, and the involvement of amyloid precursor protein and secondary messenger in improving the cognitive performance.
Fulltext Protective effect of Centella asiatica against D-galactose and aluminium chloride induced rats: Behavioral and ultrastructural approaches

Chiroma SM, Hidayat Baharuldin MT, Mat Taib CN, Amom Z, Jagadeesan S, Adenan MI, et al.

Biomed Pharmacother, 2019 Jan;109:853-864.
PMID: 30551539 DOI: 10.1016/j.biopha.2018.10.111

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder and the commonest cause of dementia among the aged people. D-galactose (D-gal) is a senescence agent, while aluminium is a known neurotoxin linked to pathogenesis of AD. The combined administration of rats with d-gal and aluminium chloride (AlCl3) is considered to be an easy and a cheap method to obtain an animal model of AD. The plant Centella asiatica (CA) is reported to exert neuroprotective effects both in vitro and in vivo. Therefore, this study explored the protective effects of CA on cognition and brain ultrastructure in d-gal and AlCl3 induced rats.
MATERIALS AND METHODS: Rats were exposed to d-gal 60 mg/kg/b.wt/day + AlCl3 200 mg/kg/b.wt/day and CA (200, 400 and 800 mg/kg/b.wt/day) and 1 mg/kg/b.wt/day of donepezil for 70 days. Different cognitive paradigms viz. T maze spontaneous alternation, modified elevated plus maze and novel object recognition test, were used to evaluate full lesions of the hippocampus, spatial learning and memory and non-spatial learning and memory respectively. Nissl's staining was used to determine the survival of hippocampus CA1 pyramidal cells, while transmission electron microscopy was used to check the ultrastructural changes.
RESULTS: The results revealed that d-gal and AlCl3 could significantly impair behavior and cognitive functions, besides causing damage to the hippocampal CA1 pyramidal neurons in rats. In addition, it also caused ultrastructural morphological alterations in rat hippocampus. Conversely, co-administration o;f CA, irrespective of the dosage used, alleviated the cognitive impairments and pathological changes in the rats comparable to donepezil.
CONCLUSION: In conclusion the results suggest that CA could protect cognitive impairments and morphological alterations caused by d-gal and AlCl3 toxicity in rats. Biochemical and molecular studies are ongoing to elucidate the probable pharmacodynamics of CA.
Fulltext WIN55,212-2 Attenuates Cognitive Impairments in AlCl3 + d-Galactose-Induced Alzheimer's Disease Rats by Enhancing Neurogenesis and Reversing Oxidative Stress

Mahdi O, Chiroma SM, Hidayat Baharuldin MT, Mohd Nor NH, Mat Taib CN, Jagadeesan S, et al.

Biomedicines, 2021 Sep 19;9(9).
PMID: 34572456 DOI: 10.3390/biomedicines9091270

Neurotransmission and cognitive dysfunctions have been linked to old age disorders including Alzheimer's disease (AD). Aluminium is a known neurotoxic metal, whereas d-galactose (d-gal) has been established as a senescence agent. WIN55,212-2 (WIN), is a potent cannabinoid agonist which partially restores neurogenesis in aged rats. The current study aimed to explore the therapeutic potentials of WIN on Aluminium chloride (AlCl3) and d-gal-induced rat models with cognitive dysfunction. Healthy male albino Wistar rats weighing between 200-250 g were injected with d-gal 60 mg/kg intra peritoneally (i.p), while AlCl3 (200 mg/kg) was orally administered once daily for 10 consecutive weeks. Subsequently, from weeks 8-11 rats were co-administered with WIN (0.5, 1 and 2 mg/kg/day) and donepezil 1 mg/kg. The cognitive functions of the rats were assessed with a Morris water maze (MWM). Furthermore, oxidative stress biomarkers; malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and neurogenesis markers: Nestin and glial fibrillary acidic protein (GFAP) were also evaluated, as well as the histology of the hippocampus. The results revealed that rats exposed to AlCl3 and d-gal alone showed cognitive impairments and marked neuronal loss (p < 0.05) in their hippocampal conus ammonis 1 (CA1). Additionally, a significant decrease in the expressions of GFAP and Nestin was also observed, including increased levels of MDA and decreased levels of SOD and GSH. However, administration of WIN irrespective of the doses given reversed the cognitive impairments and the associated biochemical derangements. As there were increases in the levels SOD, GSH, Nestin and GFAP (p < 0.05), while a significant decrease in the levels of MDA was observed, besides attenuation of the aberrant cytoarchitecture of the rat's hippocampi. The biochemical profiles of the WIN-treated rats were normal. Thus, these findings offer possible scientific evidence of WIN being an effective candidate in the treatment of AD-related cognitive deficits.
Regulatory role of the endocannabinoid system on glial cells toward cognitive function in Alzheimer's disease: A systematic review and meta-analysis of animal studies

Kamaruzzaman MA, Romli MH, Abas R, Vidyadaran S, Hidayat Baharuldin MT, Nasaruddin ML, et al.

Front Pharmacol, 2023;14:1053680.
PMID: 36959856 DOI: 10.3389/fphar.2023.1053680

Objective: Over the last decade, researchers have sought to develop novel medications against dementia. One potential agent under investigation is cannabinoids. This review systematically appraised and meta-analyzed published pre-clinical research on the mechanism of endocannabinoid system modulation in glial cells and their effects on cognitive function in animal models of Alzheimer's disease (AD). Methods: A systematic review complying with PRISMA guidelines was conducted. Six databases were searched: EBSCOHost, Scopus, PubMed, CINAHL, Cochrane, and Web of Science, using the keywords AD, cannabinoid, glial cells, and cognition. The methodological quality of each selected pre-clinical study was evaluated using the SYRCLE risk of bias tool. A random-effects model was applied to analyze the data and calculate the effect size, while I2 and p-values were used to assess heterogeneity. Results: The analysis included 26 original articles describing (1050 rodents) with AD-like symptoms. Rodents treated with cannabinoid agonists showed significant reductions in escape latency (standard mean difference [SMD] = -1.26; 95% confidence interval [CI]: -1.77 to -0.76, p < 0.00001) and ability to discriminate novel objects (SMD = 1.40; 95% CI: 1.04 to 1.76, p < 0.00001) compared to the control group. Furthermore, a significant decrease in Aβ plaques (SMD = -0.91; 95% CI: -1.55 to -0.27, p = 0.006) was observed in the endocannabinoid-treated group compared to the control group. Trends were observed toward neuroprotection, as represented by decreased levels of glial cell markers including glial fibrillary acid protein (SMD = -1.47; 95% CI: -2.56 to -0.38, p = 0.008) and Iba1 (SMD = -1.67; 95% CI: -2.56 to -0.79, p = 0.0002). Studies on the wild-type mice demonstrated significantly decreased levels of pro-inflammatory markers TNF-α, IL-1, and IL-6 (SMD = -2.28; 95% CI: -3.15 to -1.41, p = 0.00001). Despite the non-significant decrease in pro-inflammatory marker levels in transgenic mice (SMD = -0.47; 95% CI: -1.03 to 0.08, p = 0.09), the result favored the endocannabinoid-treated group over the control group. Conclusion: The revised data suggested that endocannabinoid stimulation promotes cognitive function via modulation of glial cells by decreasing pro-inflammatory markers in AD-like rodent models. Thus, cannabinoid agents may be required to modulate the downstream chain of effect to enhance cognitive stability against concurrent neuroinflammation in AD. Population-based studies and well-designed clinical trials are required to characterize the acceptability and real-world effectiveness of cannabinoid agents. Systematic Review Registration: [https://inplasy.com/inplasy-2022-8-0094/], identifier [Inplasy Protocol 3770].