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.
Psychopharmacology (Berl)
; 235(10): 2809-2822, 2018 Oct.
Article
em En
| MEDLINE
| ID: mdl-30027497
ABSTRACT
RATIONALE 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. OBJECTIVE:
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 Aß plaque production have been investigated on the intracerebroventricular (icv) injection of streptozotocin (STZ)-induced memory deficits in rats.METHODS:
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 (Aß) plaque, and neuronal loss were determined by ELISA Kit, Congo red staining, and Nissl staining, respectively.RESULTS:
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 Aß plaques production in the brain, whereas treatment with NAD-299, TCB-2, and NAD-299 + TCB-2 reduced Aß 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.CONCLUSION:
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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Aprendizagem da Esquiva
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Benzopiranos
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Compostos Bicíclicos com Pontes
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Placa Amiloide
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Hipocampo
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Transtornos da Memória
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Metilaminas
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article