Memantine treatment prevents okadaic acid induced neurotoxicity at the systemic and molecular levels

Abstract

The present study was designed to investigate the effects of okadaic acid intracerebroventricular (ICV) injection on memory function and expression level of α7 subunit of nicotinic acetylcholine receptor (nAChR) and NR2B subunit of NMDA glutamate receptors in the hippocampus, as well as effect of the antidementic drug memantine on okadaic acid induced changes at systemic and molecular levels in rats. Okadaic acid was dissolved in artificial cerebrospinal fluid (aCSF) and injected ICV 200 ng/10 μl. Vehicle control received 10 μl of aCSF ICV bilaterally. Control and okadaic acid injected rats were divided into two subgroups: treated i.p. with saline or memantine (5 mg/kg daily for 13 days starting from the day of okadaic acid injection). Rats were trained in the dual-solution plus-maze task that can be solved by using place or response strategies. The Western immunoblotting was used to determine relative amount of hippocampal receptors protein levels. Obtained data revealed that okadaic acid ICV injected rats were severely impaired at acquiring the place version of the maze accompanied by significant decline in hippocampal α7 subunit of nACh receptors protein levels. Memantine treatment can prevent okadaic acid induced impairment of hippocampal-dependent spatial memory and accompanied by modulation of the expression level of α7 subunit of nACh and NR2B subunit of NMDA receptors in the hippocampus. Thus, our results support the presumption that α7 nACh receptors may play an important role in the cognitive enhancer effects of memantine and emphasize the role of cholinergic–glutamatergic interactions in memory.

Kolaviron neuroprotective effect against okadaic acid-provoked cognitive impairment

“…On this basis, selected doses for kolaviron in this study were far lower than its LD50 dose and seem safe for therapeutic purposes. Dose of OA (200 ng/rat) was in accordance to an earlier report on its neurotoxicity in the rat [ 32 ]. At 4th week post-surgery, animals were evaluated in behavioral tasks.…”

Alpha7 nicotinic‐N‐methyl‐D‐aspartate hypothesis in the treatment of schizophrenia and beyond

“…“Fishing” RCTs with other medications with different mechanisms of actions were not likely successful. Most of the RCTs in schizophrenia have targeted mechanisms outside of glutamatergic and cholinergic systems (Aigner, 1995; Dashniani et al, 2020) and failure was inevitable (Girgis et al, 2019). Specifically, modulating NMDA (Duncan, Sheitman, & Lieberman, 1999) and α7nACh receptors (Bencherif, Stachowiak, Kucinski, & Lippiello, 2012) concurrently (Geerts & Grossberg, 2006; Grossberg, Edwards, & Zhao, 2006) may improve positive, cognitive, and negative symptoms concurrently (Bencherif et al, 2012; Duncan et al, 1999; Koola, Looney, Hong, Pillai, & Hou, 2020).…”