Neuroprotective effect of low-dose paracetamol treatment against cognitive dysfunction in d-galactose-induced aging mice
Background: Aging is closely associated to several deleterious conditions and cognitive impairment. Administration of low-dose paracetamol (APAP) has previously been reported to improve cognitive performance in both human and animal studies. However, the altered cognitive effects of low-dose APAP tr...
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| Format: | Article |
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Elsevier
2022-10-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844022023969 |
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| author | Laddawan Lalert Supang Maneesri le-Grand Tachpon Techarang Soontaraporn Huntula Chuchard Punsawad |
| author_facet | Laddawan Lalert Supang Maneesri le-Grand Tachpon Techarang Soontaraporn Huntula Chuchard Punsawad |
| author_sort | Laddawan Lalert |
| collection | DOAJ |
| description | Background: Aging is closely associated to several deleterious conditions and cognitive impairment. Administration of low-dose paracetamol (APAP) has previously been reported to improve cognitive performance in both human and animal studies. However, the altered cognitive effects of low-dose APAP treatment in the aging brain have not been elucidated. Objectives: The purpose of this study was to determine whether low-dose APAP treatment improves cognitive dysfunction in a d-galactose (d-gal)-induced aging model. Materials and methods: APAP (15 and 50 mg/kg p.o.) and vitamin E (Vit E 100 mg/kg p.o.) were administered once daily to d-gal-injected mice (200 mg/kg s.c.) for 6 weeks. The elevated plus maze (EPM), open field, novel object recognition (NOR), and Morris water maze (MWM) tests, respectively, were used to measure altered neurobehavioral functions, including anxiety-like behavior and exploratory locomotor activity, as well as learning and memory performance. The gene transcription of brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling in brain tissues was evaluated by real-time polymerase chain reaction. Results: Compared to the control, d-gal significantly decreased exploratory locomotor activity and NOR and MWM performance but did not significantly change the activity in the EPM test. However, APAP50 and Vit E significantly reversed the effects of d-gal injection on exploratory locomotor activity. In addition, low-dose APAP (15 and 50 mg/kg) and Vit E significantly improved the reduction in NOR and MWM performance induced by d-gal. Real-time polymerase chain reaction analysis revealed that the mRNA expression of BDNF, neurotrophic tyrosine receptor kinase (NTRK), which is the gene coding TrkB receptor, and cAMP response element-binding protein (CREB) was significantly decreased in the frontal cortex and hippocampus of the d-gal mice. However, APAP50 and Vit E significantly increased BDNF and NTRK mRNA expression in both the frontal cortex and the hippocampus. A lower dose of APAP (15 mg/kg) significantly elevated the mRNA expression of NTRK, but only in the hippocampus. Moreover, APAP50 significantly increased CREB mRNA expression in the frontal cortex and hippocampus. Conclusion: Low-dose APAP treatment has a neuroprotective effect on cognitive dysfunction in the d-gal aging model, and the underlying molecular mechanisms depend on the activation of BDNF/TrkB signaling. |
| first_indexed | 2024-04-12T15:17:48Z |
| format | Article |
| id | doaj.art-c5b92a98c01c4f199c2edf6b99f5122c |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-12T15:17:48Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-c5b92a98c01c4f199c2edf6b99f5122c2022-12-22T03:27:34ZengElsevierHeliyon2405-84402022-10-01810e11108Neuroprotective effect of low-dose paracetamol treatment against cognitive dysfunction in d-galactose-induced aging miceLaddawan Lalert0Supang Maneesri le-Grand1Tachpon Techarang2Soontaraporn Huntula3Chuchard Punsawad4Department of Medical Science, School of Medicine, Walailak University, Nakhon Si Thammarat 80160, Thailand; Research Center in Tropical Pathobiology, Walailak University, Nakhon Si Thammarat 80160, Thailand; Corresponding author.Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Medical Science, School of Medicine, Walailak University, Nakhon Si Thammarat 80160, Thailand; Research Center in Tropical Pathobiology, Walailak University, Nakhon Si Thammarat 80160, ThailandDepartment of Sport and Exercise Science, School of Medicine, Walailak University, Nakhon Si Thammarat 80160, Thailand; Research Center in Tropical Pathobiology, Walailak University, Nakhon Si Thammarat 80160, ThailandDepartment of Medical Science, School of Medicine, Walailak University, Nakhon Si Thammarat 80160, Thailand; Research Center in Tropical Pathobiology, Walailak University, Nakhon Si Thammarat 80160, ThailandBackground: Aging is closely associated to several deleterious conditions and cognitive impairment. Administration of low-dose paracetamol (APAP) has previously been reported to improve cognitive performance in both human and animal studies. However, the altered cognitive effects of low-dose APAP treatment in the aging brain have not been elucidated. Objectives: The purpose of this study was to determine whether low-dose APAP treatment improves cognitive dysfunction in a d-galactose (d-gal)-induced aging model. Materials and methods: APAP (15 and 50 mg/kg p.o.) and vitamin E (Vit E 100 mg/kg p.o.) were administered once daily to d-gal-injected mice (200 mg/kg s.c.) for 6 weeks. The elevated plus maze (EPM), open field, novel object recognition (NOR), and Morris water maze (MWM) tests, respectively, were used to measure altered neurobehavioral functions, including anxiety-like behavior and exploratory locomotor activity, as well as learning and memory performance. The gene transcription of brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling in brain tissues was evaluated by real-time polymerase chain reaction. Results: Compared to the control, d-gal significantly decreased exploratory locomotor activity and NOR and MWM performance but did not significantly change the activity in the EPM test. However, APAP50 and Vit E significantly reversed the effects of d-gal injection on exploratory locomotor activity. In addition, low-dose APAP (15 and 50 mg/kg) and Vit E significantly improved the reduction in NOR and MWM performance induced by d-gal. Real-time polymerase chain reaction analysis revealed that the mRNA expression of BDNF, neurotrophic tyrosine receptor kinase (NTRK), which is the gene coding TrkB receptor, and cAMP response element-binding protein (CREB) was significantly decreased in the frontal cortex and hippocampus of the d-gal mice. However, APAP50 and Vit E significantly increased BDNF and NTRK mRNA expression in both the frontal cortex and the hippocampus. A lower dose of APAP (15 mg/kg) significantly elevated the mRNA expression of NTRK, but only in the hippocampus. Moreover, APAP50 significantly increased CREB mRNA expression in the frontal cortex and hippocampus. Conclusion: Low-dose APAP treatment has a neuroprotective effect on cognitive dysfunction in the d-gal aging model, and the underlying molecular mechanisms depend on the activation of BDNF/TrkB signaling.http://www.sciencedirect.com/science/article/pii/S2405844022023969Paracetamold-galactoseAgingCognitive dysfunctionBDNF/TrkB signaling |
| spellingShingle | Laddawan Lalert Supang Maneesri le-Grand Tachpon Techarang Soontaraporn Huntula Chuchard Punsawad Neuroprotective effect of low-dose paracetamol treatment against cognitive dysfunction in d-galactose-induced aging mice Heliyon Paracetamol d-galactose Aging Cognitive dysfunction BDNF/TrkB signaling |
| title | Neuroprotective effect of low-dose paracetamol treatment against cognitive dysfunction in d-galactose-induced aging mice |
| title_full | Neuroprotective effect of low-dose paracetamol treatment against cognitive dysfunction in d-galactose-induced aging mice |
| title_fullStr | Neuroprotective effect of low-dose paracetamol treatment against cognitive dysfunction in d-galactose-induced aging mice |
| title_full_unstemmed | Neuroprotective effect of low-dose paracetamol treatment against cognitive dysfunction in d-galactose-induced aging mice |
| title_short | Neuroprotective effect of low-dose paracetamol treatment against cognitive dysfunction in d-galactose-induced aging mice |
| title_sort | neuroprotective effect of low dose paracetamol treatment against cognitive dysfunction in d galactose induced aging mice |
| topic | Paracetamol d-galactose Aging Cognitive dysfunction BDNF/TrkB signaling |
| url | http://www.sciencedirect.com/science/article/pii/S2405844022023969 |
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