Abstract
Reduced bone mineral density, and muscle strength are the hallmark of aging-related motor coordination deficits and related neuropathologies. Since cerebellum regulates motor movements and balance perception of our body, therefore it may be an important target to control the age-related progression of motor dysfunctions. Dry stem powder of Tinospora cordifolia (TCP) was tested as a food supplement to elucidate its activity to attenuate age-associated locomotor dysfunctions. Intact acyclic middle-aged female rats were used in this study as the model system of the transition phase from premenopause to menopause in women along with cycling young adult rats. Normal chow or 30% High Fat Diet (HFD), supplemented with or without TCP was fed to animals for 12 weeks and then tested for locomotor performance on rotarod followed by post-sacrifice protein expression studies. In comparison to young adults, middle-aged animals showed an increase in number of falls and lesser time spent in rotarod performance test, whereas, animals given TCP supplemented feed showed improvement in performance with more pronounced effects observed in normal chow than HFD fed middle-aged rats. Further, due to its multicomponent nature TCP was found to target the expression of various markers of neuroinflammation, apoptosis, cell survival, and synaptic plasticity in the cerebellum region. The current findings suggest that TCP supplementation in the diet may prove to be a potential interventional strategy for the management of frailty and fall-associated morbidities caused by aging-related deterioration of bone mineral density, and muscle strength.
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Abbreviations
- Akt:
-
Protein kinase B
- AP-1:
-
Activator protein 1
- BAD:
-
BCL2 associated agonist of cell death
- Bax:
-
Bcl-2-associated X protein
- Bcl-xL:
-
B-cell Lymphoma-extra large
- BDNF:
-
Brain-derived neurotrophic factor
- B-TCE:
-
Butanol extract of Tinospora cordifolia
- CNS:
-
Central nervous system
- CREB:
-
CAMP-response element binding protein
- ERα/β:
-
Estrogen receptor α/β
- ERK:
-
Extracellular signal-regulated kinase
- GFAP:
-
Glial fibrillary acidic protein
- HFD:
-
High fat diet
- HFD-M:
-
HFD fed middle-aged rats
- HRP:
-
Horseradish peroxidase
- HRT:
-
Hormone replacement therapy
- THFD-M:
-
TCP supplemented high-fat diet fed middle-aged rats
- IBA1:
-
Ionized calcium binding adaptor molecule 1
- IL-1β:
-
Interleukin 1 beta
- IL-6:
-
Interleukin 6
- LFD-M:
-
Low fat diet fed middle-aged rats
- TLFD-M:
-
TCP supplemented low fat diet fed middle-aged rats
- LFD-Y:
-
Low fat diet fed young control rats
- MAPK:
-
Mitogen-activated protein kinase
- MCP-1:
-
Monocyte chemoattractant protein-1
- MPTP:
-
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
- nNOS:
-
Neuronal nitric oxide synthase
- OVX:
-
Ovariectomized
- PFC:
-
Prefrontal cortex
- SEM:
-
Standard error of mean
- SERM:
-
Selective estrogen receptor modulator
- SKA:
-
Sequentially kinetic activated
- TBST:
-
Tris buffered saline with tween
- TCE:
-
Hydroalcoholic extract of Tinospora cordifolia
- TCP:
-
Dry stem powder of Tinospora cordifolia
- TNF-α:
-
Tumour necrosis factor alpha
- Trkβ:
-
Tropomyosin receptor kinase B
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Funding
This work was supported by Department of Biotechnology, Government of India (GOI) under grant 102/IFD/SAN/ 3329/2015 to Gurcharan Kaur.
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AB, AS and GK: Conceptualized the study; GK: Funding acquisition; AB and SK: conducted the experiments; PB: helped in behavioral study; AB: collected and processed the data; AB, AS and GK: Writing, Reviewing and Editing of MS.
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All experimental protocols for animals were approved (Permission number—266/2020/12) and carried out in accordance with the institutional guidelines of 'Animal Care and Use' established by the Institutional Animal Ethical Committee of Guru Nanak Dev University, Amritsar, India.
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Bhandari, A., Kalotra, S., Bajaj, P. et al. Dietary intervention with Tinospora cordifolia improved aging-related decline in locomotor coordination and cerebellar cell survival and plasticity in female rats. Biogerontology 23, 809–824 (2022). https://doi.org/10.1007/s10522-022-09975-w
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DOI: https://doi.org/10.1007/s10522-022-09975-w