Sleep Alterations in a Mouse Model of Spinocerebellar Ataxia Type 3.

Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder showing progressive neuronal loss in several brain areas and a broad spectrum of motor and non-motor symptoms, including ataxia and altered sleep. While sleep disturbances are known to play pathophysiologic roles in other neurodegenerative disorders, their impact on SCA3 is unknown. Using spectrographic measurements, we sought to quantitatively characterize sleep electroencephalography (EEG) in SCA3 transgenic mice with confirmed disease phenotype.

Multiple cholinesterase inhibitors have antidepressant-like properties in the mouse forced swim test.

There is high clinical interest in improving the pharmacological treatment of individuals with Major Depressive Disorder (MDD). This neuropsychiatric disorder continues to cause significant morbidity and mortality worldwide, where existing pharmaceutical treatments such as selective serotonin reuptake inhibitors often have limited efficacy. In a recent publication, we demonstrated an antidepressant-like role for the acetylcholinesterase inhibitor (AChEI) donepezil in the C57BL/6J mouse forced swim test (FST).

Repurposing Cholinesterase Inhibitors as Antidepressants? Dose and Stress-Sensitivity May Be Critical to Opening Possibilities.

When stress becomes chronic it can trigger lasting brain and behavioral changes including Major Depressive Disorder (MDD). There is conflicting evidence regarding whether acetylcholinesterase inhibitors (AChEIs) may have antidepressant properties. In a recent publication, we demonstrated a strong dose-dependency of the effect of AChEIs on antidepressant-related behavior in the mouse forced swim test: whereas the AChEI donepezil indeed promotes depression-like behavior at a high dose, it has antidepressant-like properties at lower doses in the same experiment.

The cholinesterase inhibitor donepezil has antidepressant-like properties in the mouse forced swim test.

Finding new antidepressant agents is of high clinical priority given that many cases of major depressive disorder (MDD) do not respond to conventional monoaminergic antidepressants such as the selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, and monoamine oxidase inhibitors. Recent findings of effective fast-acting antidepressants indicate that there are biological substrates to be taken advantage of for fast relief of depression and that we may find further treatments in this category. In this vein, the cholinergic system may be a relatively overlooked target for antidepressant medications, given its major role in motivation and attention.