The functional effects of piperine and piperine plus donepezil on hippocampal synaptic plasticity impairment in rat model of Alzheimer's disease.

AIMS: The modulatory effects of piperine on drug metabolizing enzymes play an important role in the control of pharmacokinetic and the bioavailability properties of the administered drugs. The present study investigated the effect of piperine and piperine-donepezil co-administration on cognitive functions and synaptic plasticity at hippocampal perforant pathway (PP) to dentate gyrus (DG) synapses in an experimental model of Alzheimer's disease (AD). MATERIALS AND METHODS: Intracerebroventricularly (ICV) streptozotocin (STZ) injected rats were treated once daily with piperine, donepezil and piperine combined with donepezil for 4 weeks. Cognitive performance was evaluated using passive avoidance and Morris water maze performance tasks. Analysis of evoked field potentials was done to explore possible effects on input/output response, paired-pulse facilitation and long-term synaptic plasticity (LTP) at PP to DG synapses of hippocampus. KEY FINDINGS: Rats subjected to ICV injection of STZ exhibited cognitive deficit associated with a hippocampal oxidative stress, effects that were reversed by chronic treatment with piperine or donepezil and or piperine combined with donepezil. Chronic treatment with piperine or donepezil restored the disruptive effects of STZ on LTP without altering basal synaptic transmission. SIGNIFICANCE: We found that optimal hippocampal function is dependent on tissue redox homeostasis. Piperine might reduce the synaptotoxic effects of STZ on hippocampal synaptic neurotransmission and correspondently is a good potential for neuroprotection against oxidative damage from ICV injection of STZ. These results suggest that piperine or donepezil significantly ameliorate cognitive deficit and LTP induction by attenuating oxidative status.

Neurotoxic effects of high-dose piperine on hippocampal synaptic transmission and synaptic plasticity in a rat model of memory impairment.

In recent years, piperine has attracted much attention due to its various biological effects as a neuroprotective agent. Therefore, clarification of the possible side effects of piperine is important to identify its potential pharmacological action. Thus, the effects of piperine on the long-term plasticity of perforant pathway to dentate gyrus synapses were studied in hippocampus of an animal model of Alzheimer's disease (AD). Adult male rats were injected with intracerebroventricular (ICV) streptozotocin (STZ) bilaterally, on days 1 and 3 (3 mg/kg). The STZ-injected rats were treated with different doses of piperine for 4 weeks before being used in behavioral, electrophysiological and histopathological experiments. The passive-avoidance test was conducted on all animals in order to determine the cognitive performance. Rats were placed in a stereotaxic frame to implant a recording electrode in the hippocampal dentate gyrus and a stimulating electrode in the perforant path. Additionally, we assessed the density of survived neurons stained by cresyl violet. In this study, chronic administration of piperine low dose improved the ICV-STZ induced learning and long-term potentiation (LTP) impairments with no significant effect on baseline synaptic activity. In contrast, remarkable learning and long-term plasticity impairments were observed in rats treated by high dose of piperine in comparison to the other groups. Interestingly, this impaired hippocampal LTP was accompanied by an obvious alteration in baseline activity and significantly decreased neuronal numbers within the hippocampus. Therefore, our data provides a new understanding of the piperine supplementation effects on hippocampal electrophysiological profile although the consequences may be either beneficial or detrimental.