Neuroprotective action of diazepam at very low and moderate doses in Alzheimer's disease model rats.

Neuroprotective action of diazepam at very low and moderate doses in Alzheimer's disease model rats. Neuropharmacology. 2018 Nov 05;: Authors: Pilipenko V, Narbute K, Pupure J, Rumaks J, Jansone B, Klusa V Abstract Early manifestations of Alzheimer's disease (AD) include neuroinflammation, disrupted neurotransmission and cognitive deficits. Impairment of the GABAergic system is essentially involved in the pathogenesis of AD. Traditionally, agonists of GABAA receptors at doses above 1 mg/kg are known to possess memory impairing effects. However, we have previously found that GABAA receptor GABA site ligand muscimol at very low doses acted contrary - enhanced spatial learning/memory, as well as prevented neuroinflammation and augmented neurotransmission in AD model rats. Therefore, in the present study we focused on the assessment of the effects of non-sedative - very low (0.05 mg/kg) and moderate (1 mg/kg) - doses of diazepam, a positive allosteric modulator of benzodiazepine site of GABAA receptors. Its effects on spatial learning/memory and brain proteins related to neuroinflammation (GFAP and Iba-1), synaptic plasticity (SYP1), as well as acetylcholine breakdown and GABA biosynthesis were studied. Non-transgenic AD model rats (intracerebroventricular streptozocin injection) were used with the aim to mimic the pre-dementia stage of AD in humans. The obtained data showed that diazepam at both doses protected against streptozocin indu...
Source: Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Neuropharmacology Source Type: research