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Activation of SIRT-1 Signalling in the Prevention of Bipolar Disorder and Related Neurocomplications: Target Activators and Influences on Neurological Dysfunctions

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Abstract

SIRT-1 (silent mating-type information regulation 2 homolog-1) is a protein found in neuronal nuclei, microglia, and astrocyte cells of the brain. It is sometimes referred to as NAD + -dependent deacetylase (nicotinamide adenine dinucleotide). The activation of sirtuins (SIRT-1–7) has been shown to protect against a wide range of disorders, including neurodegenerative and neuropsychiatric disorders. SIRT-1 has gained considerable interest from these families because of its early link to long-life expansion and calorie restriction involvement. SIRT-1 is necessary for gene silencing, cell cycle regulation, fat and glucose metabolism, oxidative stress, ageing, and memory formation. In this review, we investigate the role of SIRT-1 downregulation in the progression of bipolar disorder (BD) and neurological abnormalities, as well as related neurological alterations such as genetic dysfunction, neurotransmitter imbalance, oxidative stress-induced apoptosis, and mitochondrial dysfunction. BD is a psychiatric disease distinguished by extreme mood fluctuations that range from depressive lows to manic highs. BD is a complicated disorder with numerous clinical signs and neurocomplications that produce significant behavioural problems. SIRT-1 deficiency in the brain has been demonstrated to affect the activity of its transcription factors and molecular changes, including genetic defects. SIRT-1 is now being studied as a potential therapeutic target for a range of brain disorders. A recent study also found that activating SIRT-1 signalling performs a protective effect in avoiding depression and mania-like behaviours. Furthermore, this review investigates the potential mechanisms by which SIRT-1 regulates neuronal transmission and neurogenesis. As a result of our review, we revealed that SIRT-1 activators have neuroprotective potential in BD and related neurological dysfunctions.

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Abbreviations

SIRT-1 :

Silent mating-type information regulation 2 homolog-1

NAD  +  :

Nicotinamide adenine dinucleotide

BD :

Bipolar disorder

Th17-cells :

T helper 17 cells

IL-1β :

Interleukin-1β

MDD :

Major depressive disorder

AD :

Alzheimer disease

PD :

Parkinson’s disease

MS :

Multiple sclerosis

NADH :

Nicotinamide adenine dinucleotide hydrogen

p53 :

Tumour proteins p53

FOXO1/3 :

Fork head box protein O1/3

PGC-1α :

Peroxisome proliferator-activated gamma co-activator-1 alpha

NF-kB :

Nuclear factor kappa light chain enhancer of activated B-cells

DG :

Dentate gyrus

CA3 :

Cornuammonis 3

WBC :

White blood cells

Na  +  K  +  -ATPase :

Sodium and potassium-activated adenosine triphosphatase

miR-138 :

MicroRNA-138

PPD :

Postpartum depression

NiO :

Nickel oxide

PFC :

Prefrontal cortex

CNS :

Central nervous system

AKT :

A serine/threonine-protein kinase

GSK-3 :

Glycogen synthase kinase-3

RNA :

Ribonucleic acid

NHLH-2 :

Nescient helix loop helix-2

MAO-A :

Monoamine oxidase-A

HT :

Serotonin

5-HIAA :

5-Hydroxy indole acetic acid

MPTP :

1-Methyl-4-phenyl-1, 2, 3 and 6-tetrahydropyridine

ALS :

Amyotrophic lateral sclerosis

NAc :

Nucleus accumbens

AMPK :

AMP-activated protein kinase

PKC :

Protein kinase C

IP3 :

Inositol 1,4,5 triphosphate

TNF-α :

Tumour necrosis factor-alpha

AP-1 :

Activator protein-1

ROS :

Reactive oxygen species

RNS :

Reactive nitrogen species

BSKO :

Brain-specific SIRT-1 knockout

GPCR :

G protein-coupled receptor

mRNA :

Messenger RNA

eQTL :

Expression quantitative trait loci

BDNF :

Brain-derived neurotrophic factor

CUMS :

Chronic unpredictable mild stress

ATP :

Adenosine triphosphate

HIFs :

Hypoxia-induced factors

IFN-γ :

Interferon-gamma

IL-6 :

Interleukin-6

DG-SGZ :

Dentate gyrus-subgranular zone

LPS :

Lipopolysaccharide

BAX :

Bcl-2-associated X protein

ERK1/2 :

Extracellular signalling-regulated protein kinases 1 &2

CVS :

Chronic variable stress

NRF-1 :

Nuclear respiratory factor-1

CREB :

CAMP-response element-binding protein

cAMP :

Cyclic adenosine monophosphate

NLRP3 :

NLR family pyrin domain containing 3

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Acknowledgements

The authors express their gratitude to Chairman, Mr. Parveen Garg, and Director, Dr. G. D. Gupta, ISF College of Pharmacy, Moga (Punjab), India, for their great vision and support.

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  1. Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga, 142001, Punjab, India

    Bidisha Rajkhowa, Sidharth Mehan, Pranshul Sethi & Aradhana Prajapati

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  1. Bidisha Rajkhowa
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  2. Sidharth Mehan
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BR (Bidisha Rajkhowa) and (PS) Pranshul Sethi involved in the investigation, writing-original draft, review writing; SM (Sidharth Mehan) has contributed towards conceptualization, resource gathering, supervision, writing-review and critical editions. All authors read and approved the manuscript, and all data were generated in-house and that no paper mill was used.

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Rajkhowa, B., Mehan, S., Sethi, P. et al. Activation of SIRT-1 Signalling in the Prevention of Bipolar Disorder and Related Neurocomplications: Target Activators and Influences on Neurological Dysfunctions. Neurotox Res 40, 670–686 (2022). https://doi.org/10.1007/s12640-022-00480-z

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