Effect of inhibiting melatonin biosynthesis on spatial memory retention and tau phosphorylation in rat

Abstract

We have found recently that melatonin protects SH-SY5Y neuroblastoma cells from calyculin A-induced neurofilament impairment and neurotoxicity. In the present study, we further investigated the in vivo effect of inhibiting melatonin biosynthesis on spatial memory retention and tau phosphorylation in rats and the potential underlying mechanisms by using haloperidol, a specific inhibitor of 5-hydroxyindole-O-methyltransferase, and a key enzyme in melatonin biosynthesis. We have found that injection of haloperidol into the lateral ventricle and into peritoneal cavity compromises spatial memory retention of rats and induces hyperphosphorylation of microtubule-associated protein tau at tau-1 (Ser199/Ser202) and PHF-1 (Ser396/Ser404) epitopes. At mean time, the activity of protein phosphatase-2A (PP-2A), a deficit phosphatase in the Alzheimer's disease brain and superoxide dismutase decreases with an elevated level of malondialdehyde. Supplementation with melatonin by prior injection for 1 wk and reinforcement during the haloperidol administration significantly improves memory retention deficits, arrests tau hyperphosphorylation and oxidative stress, and restores PP-2A activity. These results strongly support the involvement of decreased melatonin in Alzheimer-like spatial memory impairment and tau hyperphosphorylation, and PP-2A may play a role in mediating aberrant melatonin-induced lesions.

Reactive Oxygen Species in the Regulation of Synaptic Plasticity and Memory

“…Melatonin and learning and memory. Similar to what has been observed in LTP studies, behavioral studies indicate that melatonin has a detrimental effect on learning and memory performance (242,355,375,466). On the other hand, in studies performed under situations of oxidative stress, the effect of melatonin on learning and memory deficits is for the most part positive.…”

Morfología de la Glándula Pineal: Revisión de la Literatura

“…La glándula pineal es una pequeña estructura que en la gran mayoría de los vertebrados se encuentra ubicada en el techo del diencéfalo, su principal función es regular los ritmos circadianos (sueño-vigilia), secretar melatonina, hormona con fuerte efecto sobre la acción gonadal, además de efectos oncostático, geroprotector, antioxidante (Stehle et al, 2011), así como un importante rol inmunoprotector (Arias et al, 2003), también ha sido descrita en el tratamiento de enfermedades degenerativas, tales como la enfermedad de Alzheimer (Zhu et al, 2004).…”

Therapeutical Implications of Melatonin in Alzheimer’s and Parkinson’s Diseases

“…The inhibition of melatonin biosynthesis in rats not only resulted in impairment of spatial memory but also induced an increase in tau phosphorylation, an effect prevented by melatonin supplementation (Zhu et al 2004 ). Melatonin also prevented the oxidative damage and organelles injury found in animal models.…”