Simvastatin reverses the downregulation of M1/4 receptor binding in 6-hydroxydopamine-induced parkinsonian rats: The association with improvements in long-term memory

Abstract

. (2014). Simvastatin reverses the downregulation of M1/4 receptor binding in 6-hydroxydopamine-induced parkinsonian rats: the association with improvements in long-term memory. Neuroscience, 267 57-66.Simvastatin reverses the downregulation of M1/4 receptor binding in 6-hydroxydopamine-induced parkinsonian rats: the association with improvements in long-term memory AbstractBackground It is believed that muscarinic M1/4 receptors are closely correlated to the dopaminergic system and are strongly involved in the pathogenesis of Parkinson's disease (PD). In addition to regulating lipid metabolism and protection from stroke, statins have been used to regulate the declined cognition. We aimed to explore the regional changes in M1/4 receptors in the 6-hydroxydopamine (6-OHDA)-lesioned rat brain. Methods PD rat model was set up by injecting 6-OHDA into the unilateral medial forebrain bundle; while simvastatin (10 mg/kg/day) or saline was orally administrated for 3 weeks, respectively. Long-term memory was measured using the Morris water maze.[3H]pirenzepine binding autoradiography was applied to investigate the alterations of M1/4 receptors in the PD rat brains. Results 6-OHDA induced long-term memory deficits along with downregulation of M1/4 receptors in the hippocampus, the medial amygdala, the posteromedial cortical and the piriform cortex; simvastatin administration significantly ameliorated the impaired memory and reversed the downregulation of M1/4 receptors in the examined brain regions. Profound positive correlations were verified between the decline in long-term memory activity and the restoration of M1/4 receptors in different brain regions after simvastatin treatment. Conclusions/significance Our results provide strong evidence that M1/4 receptor modulation after simvastatin administration did, at least partially, contribute to the improvement in the long-term memory in 6-OHDA-induced PD rats. These results provide a possible mechanism for simvastatin treatment in psycho-neurological diseases such as PD via M1/4 receptors.

Reversal effect of simvastatin on the decrease in cannabinoid receptor 1 density in 6-hydroxydopamine lesioned rat brains

“…These results combined with another study that was published by our group on the same rats and treatments in this study found longterm memory impairments were prevented in 6-OHDA rats treated with simvastatin [56]. By testing the rats in a Morris Water Maze, it was observed that 6-OHDA rats treated with simvastatin (10 mg/kg/day) had a significantly shorter total distance travelled that resembled the control rats.…”

Simvastatin as a Potential Disease-Modifying Therapy for Patients with Parkinson’s Disease: Rationale for Clinical Trial, and Current Progress

“…They argued that chronic inflammation offers a clear biochemical mechanism which can promote the development of PD. Huang et al [ 44 ] recently showed in multiple models that Simvastatin ameliorated memory deficits in patients with Alzheimer’s disease as well as in laboratory models of AD, and that it achieved this through reduction of mRNA expression of inflammatory cytokines and mediators as well as by improving neuronal survival, supporting earlier work by Wang et al [ 45 ].…”

Dietary Galacto‐Oligosaccharides and Resistant Starch Protect Against Altered CB1 and 5‐HT1A and 2A Receptor Densities in Rat Brain: Implications for Preventing Cognitive and Appetite Dysfunction During a High‐Fat Diet

“…Quantification of binding sites was performed using a high‐resolution Beta Imager (BioSpace, Paris, France) according to our previous studies . Briefly, sections were placed in a sample holder inside the detection chamber of the Beta Imager.…”