The Effect of Naringin on Cognitive-Behavioral Functions, CREB/BDNF Signaling, Cholinergic Activity, and Neuronal Density in the Hippocampus of an MSG-Induced Obesity Rat Model.

Abstract

The global rise in obesity and overweight over the past few decades has led to numerous associated disorders, including cognitive deficits. This study evaluate investigates the effects of Naringin (Nar) on memory and learning, anxiety-like behaviors, brain-derived neurotrophic factor (BDNF), cAMP responsive element binding protein (CREB), acetylcholinesterase (AChE) activity, and neuronal density in the CA₁/CA₃ subfields of the hippocampus in an MSG-induced obese obesity rat model. Forty-eight male Wistar rat pups were randomly divided into four groups: Control, MSG, MSG + Nar50, and MSG + Nar100. MSG (4 g/kg BW) was administered subcutaneously in the cervical region from PND 2 to PND10, while Nar (50 mg/kg BW and 100 mg/kg BW) was administered orally from PND30 to PND42. After the treatment period, cognitive (working memory and passive avoidance) and anxiety-related tests (elevated plus maze and novelty-suppressed feeding test) were performed. Subsequently, hippocampal protein level of BDNF and CREB/BDNF gene expression, AChE activity and neuronal density in the CA₁ and CA₃ regions of the hippocampus were measured. Relative to the MSG group, the Nar-treated rats demonstrated improvements in spatial working memory, reduced anxiety-related behaviors, elevated hippocampal CREB and BDNF genes and BDNF protein levels, and reduced AChE activity. Additionally, Nar treatment increased neuronal density in the CA₁/CA₃ subfields of the hippocampus. These findings suggest that Nar enhances cognitive function and mitigates anxiety in MSG-induced obese rats by modulating CREB/BDNF signaling pathway, inhibiting AChE, and exerting neuroprotective effects in the hippocampus.