RESUMEN
Bipolar disorder (BD) is a chronic mental illness characterized by mood fluctuations that range from depressive lows to manic highs. Several studies have linked the downregulation of SIRT-1 (silent mating type information regulation-2 homologs) signaling to the onset of BD and other neurological dysfunctions. This research aimed to look into the neuroprotective potential of Solanesol (SNL) in rats given ICV-Ouabain injections, focusing on its effect on SIRT-1 signaling activation in the brain. Ouabain, found in hypothalamic and medullary neurons, is an endogenous inhibitor of brain Na+/K+ ATPase. The inhibition of brain Na+/K+ ATPase by Ouabain may also result in changes in neurotransmission within the central nervous system. SNL is a Solanaceae family active phytoconstituent produced from the plant Nicotiana tabacum. SNL is used as a precursor for the production of CoQ10 (Coenzyme Q10), a powerful antioxidant and neuroprotective compound. In the current study, lithium (Li), an important mood stabilizer drug, was used as a control. This study looked at the neuroprotective potential of SNL at dosages of 40 and 80 mg/kg in ICV-OUA injections that caused BD-like neurobehavioral and neurochemical defects in Wistar rats. Wistar rats were placed into eight groups (n = 6) and administered 1 mM/0.5 µL ICV-OUA injections for three days. Neurochemical assessments were done in rat brain homogenates, CSF, and blood plasma samples at the end of the experiment protocol schedule. Long-term SNL and lithium administration have been shown to decrease the number of rearing and crossings and reduce time spent in the center, locomotor activities, and immobility time. Solansesol treatment gradually raises the amount of Na+/K+ ATPase, limiting the severity of behavioural symptoms. These findings also revealed that SNL increases the levels of SIRT-1 in CSF, blood plasma, and brain homogenate samples. Moreover, in rat brain homogenates and blood plasma samples, SNL modulates apoptotic markers such as Caspase-3, Bax (pro-apoptotic), and Bcl-2 (anti-apoptotic). Mitochondrial-ETC complex enzymes, including complex-I, II, IV, V, and CoQ10, were also restored following long-term SNL treatment. Furthermore, SNL lowered inflammatory cytokines (TNF-α, IL-1ß) levels while restoring neurotransmitter levels (serotonin, dopamine, glutamate, and acetylcholine) and decreasing oxidative stress markers. Histological examinations also validated Solanesol's protective effect. As a result, our findings suggest that SNL, as a SIRT-1 signalling activator, may be a promising therapeutic approach for BD-like neurological dysfunctions.
RESUMEN
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.