Thymelaea lythroides extract attenuates microglial activation and depressive-like behavior in LPS-induced inflammation in adult male rats.

Thymelaea lythroides extract is widely used as a traditional folk medicine in Morocco, especially for the treatment of diabetes, rheumatism and Inflammatory disease. The aim of the study is to evaluate the possible effect of methanolic extract of Thymelaea lythroides in repressing the inflammatory responses and long-lasting depression-like behavior associated with neuroinflammation in adult rats after neonatal LPS exposure. Male rat pups were treated systemically with either LPS (250??g/kg) or vehicle (phosphate buffer saline) on postnatal day 14. Six hours later, the LPS groups were assigned to intraperitoneal (ip) injection of Minocycline (50?mg/kg) or Thymelaea lythroides (200?mg/kg). Thereafter, in adulthood (postnatal days 90-97), the spontaneous locomotor activity and depression-like behavior were assessed successively in open field and forced swim tests. The levels of proinflammatory cytokines, oxidative damage, and activation of microglia were determined in the hippocampus (HP) of male rats on (PND90-97). Our results showed that open field hypoactivity and increased immobility period in LPS-induced adult rats were normalized on treatment with Thymelaea lythroides and minocycline. Both treatments attenuate the overactivated microglial cells in the CA1 and CA3 of hippocampus (HP) and significantly reduced the oxidative-nitrosative stress markers and cytokine (TNF ?) production in the HP. Thymelaea lythroides seems to have similar neuroprotective effects to Minocycline, and such protection may be due to: reduction of oxidative stress, upregulation of inflammatory mediators production, antidepressant behavior which all are associated with neuroinflammation.

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

BACKGROUND: Systemic inflammation induced by neonatal infection may result as long-term hyper-activation of microglial cells followed by an overproduction of pro-inflammatory cytokines, such as tumor necrosis factor-alpha, nitric oxide and lipid peroxidation. Those inflammation mediators can trigger behavioral disruption and/or cognitive disorders. OBJECTIVE: The present work aims to evaluate the effect of melatonin (a cytokine release modulator and antioxidant agent) in the reduction of the prefrontal microglia activation and depressive-like behaviors induced by lipopolysaccharide (LPS) injection in adult rats. RESULTS: The effect of melatonin (5 mg/kg) was compared to minocycline (50 mg/kg), a well-known anti-inflammatory drug with potent inhibitory effect on microglial activation. Our results showed that LPS injection induced a significant increase in prefrontal cortex tumor necrosis factor-alpha and nitric oxide levels. Furthermore, lipid peroxidation and microglial activation were highly increased in the prefrontal cortex compared to control. The melatonin treatment induced a significant decrease on nitric oxide and lipid peroxidation levels in the prefrontal cortex and significant decrease on tumor necrosis factor-alpha and microglia activation. Melatonin can also induce a significant reduction in the anxiety and depression-like effect induced by PND9 LPS administration. CONCLUSION: 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.