Postnatal melatonin treatment protects against affective disorders induced by early-life immune stimulation by reducing the microglia cell activation and oxidative stress

Abstract

Our results demonstrated that melatonin possesses potent protective effect against the depression and anxiety induced by LPS. The underlying effect of melatonin is probably due to the reduction of nitric oxide toxic effect and lipid peroxidation in addition to its anti-inflammatory effect.

Repetitive Neonatal Erythropoietin and Melatonin Combinatorial Treatment Provides Sustained Repair of Functional Deficits in a Rat Model of Cerebral Palsy

“…Similarly, complimenting the EPOR distribution on glia, and neurons, and the importance of receptor/ligand balance in the developing brain ( 55 ), MLT receptors, MT1 and MT2, are present in regions of the brain that are important to cognition and memory, including the hippocampus and frontal cortex and are similarly regulated by endogenous MLT ( 69 , 87 , 95 , 96 ). In rodents, several studies have reported improved social behavior, anxiolytic, antidepressant, and memory-facilitating effects of exogenous MLT related to modulation of essential neurotransmitters and their receptors, including GABAergic, dopaminergic, glutamatergic, cholinergic, and noradrenergic transmission ( 69 , 97 – 100 ). Consistent with our data, studies in mice confirm a MLT-induced decrease in open field hyperlocomotion ( 69 ).…”

Pineal Calcification, Melatonin Production, Aging, Associated Health Consequences and Rejuvenation of the Pineal Gland

“…This association is connected with the melatonin levels synthesized by this gland. It is well established that melatonin is a neuroprotector with its potent antioxidant function and anti-inflammatory activity [ 171 , 172 , 173 , 174 , 175 , 176 ]. The brain is rich in lipid, lacks the antioxidative enzyme, catalase, and consumes large quantity of oxygen (roughly 20% of the total oxygen consumed by the brain with 1% of the total body weight).…”

Microglial Function in the Effects of Early-Life Stress on Brain and Behavioral Development

“…The authors suggested that this increased neuroinflammatory response to bacterial molecules in neonatal but not periadolescent pups may underlie the sensitivity to infection that characterizes early postnatal neurodevelopment. Additionally, early LPS administration has been shown to have a long-lasting effect on microglial responses: injection applied during the first or second postanal week increases microglial cell density, IBA-1 expression, and hypertrophic morphology later in life, registered in the PFC [101,102], HIP [101,103,104], and substantia nigra [105][106][107]. Moreover, high colocalization between apoptosis-associated speck-like protein (ASC, part of the NLRP3 inflammasome) and IBA-1 was found in adolescent brains from LPS-exposed rats [101], suggesting an effect on apoptotic pathways in microglia.…”

“…Moreover, they demonstrated that microglial activation was driven by alcohol-induced apoptotic cell death, and not by the direct effects of alcohol on microglia [88]. In an experiment of neonatal immune activation, minocycline pretreatment before LPS injection failed to rescue the locomotor, anxiety, and depression-like behavioral alterations in adult mice [102]. However, a more extended treatment (minocycline exposure pre-and post LPS injection) significantly attenuated LPS-induced brain injury and improved neurobehavioral performance in P21 rats [106].…”

“…Preclinical work suggests that melatonin can reduce microglial alterations in brain regions such as the AMY, hypothalamus, ipsilateral basal cortex, and HIP [139][140][141]. Melatonin can modulate microglia density and morphology as well as phagocytic response to LPS in the HIP both in adulthood [142,143] and in early life [102]. Furthermore, melatonin treatment during gestation has attenuated microglia activation in the HIP as a result of umbilical cord occlusion in early life, and kainic acid administration via intraperitoneal injection in adulthood [144,145].…”