Journal Article

The effect of NAD-299 and TCB-2 on learning and memory, hippocampal BDNF levels and amyloid plaques in Streptozotocin-induced memory deficits in male rats

Rohani, Ali Haeri, Asl, Sara Soleimani, Shahidi, Siamak, Komaki, Alireza, Afshar, Simin

2018

Overview

Alzheimer's disease (AD) is the most common form of dementia characterized by a progressive decline in cognitive function. The serotonergic system via the 5-HT1A receptor and 5-HT2A receptor is proposed to affect the cognitive process. In the present study, the effects of NAD-299 (5-HT1AR antagonist) and TCB-2 (5-HT2AR agonist) on learning and memory processes, hippocampal brain-derived neurotrophic factor (BDNF) levels, neuronal necrosis, and Aβ plaque production have been investigated on the intracerebroventricular (icv) injection of streptozotocin (STZ)-induced memory deficits in rats. Fifty-four adult male Wistar rats (250-300 g) were divided into six groups (n = 9 in each group): control, sham-operated, AD (icv-STZ (3 mg/kg, 10 μl)), AD+NAD-299 (5 μg/1 μl icv for 30 days), AD+TCB-2 (5 μg/1 μl icv for 30 days), and AD+NAD-299 + TCB-2 (NAD-299 (5 μg/0.5 μl icv) and TCB-2 (5 μg/0.5 μl icv) for 30 days). Following the treatment period, rats were subjected to behavioral tests of learning and memory. Then, hippocampal BDNF, amyloid-beta (Aβ) plaque, and neuronal loss were determined by ELISA Kit, Congo red staining, and Nissl staining, respectively. The results of behavioral tests showed that icv-STZ injection decreased the discrimination index in the novel object recognition (NOR) test. In the passive avoidance learning (PAL) task, icv-STZ injection significantly decreased step-through latency (STLr) and increased time spent in dark compartment (TDC). Treatment with NAD-299, TCB-2, and NAD-299 + TCB-2 attenuated the STZ-induced memory impairment in both NOR and PAL tasks. icv-STZ induced a decrease in hippocampal BDNF levels and increased Aβ plaques production in the brain, whereas treatment with NAD-299, TCB-2, and NAD-299 + TCB-2 reduced Aβ plaques in the brain and increased the hippocampal BDNF level. Results of Nissl staining showed that icv-STZ injection increased neuronal loss in the hippocampus, while treatment with NAD-299, TCB-2, and NAD-299 + TCB-2 reduced hippocampal neurodegeneration. These findings suggest that 5-HT1AR blockade by NAD-299 and 5-HT2AR activation by TCB-2 improve cognitive dysfunction in icv-STZ-treated rats, and these drugs may potentially prevent the progression of AD.

• Publisher: Springer,Springer Nature B.V
• Subject: Advertising executives / Alzheimer's disease / Amyloid beta-protein / Animals / Avoidance learning / Avoidance Learning - drug effects / Avoidance Learning - physiology / Benzopyrans - pharmacology / Benzopyrans - therapeutic use / Brain-Derived Neurotrophic Factor / Bridged Bicyclo Compounds - pharmacology / Bridged Bicyclo Compounds - therapeutic use / Cognition - drug effects / Cognition - physiology / Cognitive ability / Complications and side effects / Dementia disorders / Development and progression / Disease Models, Animal / Drug therapy / Enzyme-linked immunosorbent assay / Health aspects / Hippocampus / Hippocampus - drug effects / Hippocampus - metabolism / Injection / Latency / Learning / Male / Measurement / Memory / Memory Disorders - chemically induced / Memory Disorders - drug therapy / Memory Disorders - metabolism / Methylamines - pharmacology / Methylamines - therapeutic use / NAD / Neurodegeneration / Neurons / Neurophysiology / Neurotrophic functions / Pattern recognition / Physiological aspects / Plaque, Amyloid - chemically induced / Plaque, Amyloid - drug therapy / Plaque, Amyloid - metabolism / Random Allocation / Rats / Rats, Wistar / Receptor, Serotonin, 5-HT2A - metabolism / Rodents / Senile plaques / Serotonin / Serotonin agents / Serotonin S1 receptors / Serotonin S2 receptors / Streptozocin / Streptozocin - toxicity / Testing