Effects of Different Lipopolysaccharide Doses on Short- and Long-Term Spatial Memory and Hippocampus Morphology in an Experimental Alzheimer’s Disease Model

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia. Various animal models are widely used to investigate its underlying mechanisms, including lipopolysaccharide (LPS)-induced neuroinflammation models. Aim: In this study, we aimed to investigate the effect of different doses (0.25, 0.5, and 0.75 mg/kg) of LPS on short- and long-term spatial memory and hippocampal morphology in an experimental AD mouse model. Materials and methods: Twenty-four adult male Swiss mice (SWR/J) weighing 18–25 g were divided into four groups: control, 0.25 mg/kg LPS, 0.50 mg/kg LPS, and 0.75 mg/kg LPS. All groups were treated with LPS or vehicle for 7 days. Behavioral tests were started (Morris water maze for 6 days and Y maze for 1 day) on the last 2 days of injections. After the behavioral procedures, tissues were collected for further histological investigations. Result: All LPS doses induced significant short- and long-term spatial memory impairment in both the Y maze and Morris water maze compared with the control group. Furthermore, histological examination of the hippocampus indicated degenerating neurons in both the 0.50 mg/kg and 0.75 mg/kg LPS groups, while the 0.25 mg/kg LPS group showed less degeneration. Conclusion: our results showed that 0.75 mg/kg LPS had a greater impact on early-stage spatial learning memory and short-term memory than other doses. Our behavioral and histological findings suggest 0.75 mg/kg LPS as a promising dose for LPS-induced AD models

Effects of Different Lipopolysaccharide Doses on Short- and Long-Term Spatial Memory and Hippocampus Morphology in an Experimental Alzheimer’s Disease Model

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia. Various animal models are widely used to investigate its underlying mechanisms, including lipopolysaccharide (LPS)-induced neuroinflammation models. Aim: In this study, we aimed to investigate the effect of different doses (0.25, 0.5, and 0.75 mg/kg) of LPS on short- and long-term spatial memory and hippocampal morphology in an experimental AD mouse model. Materials and methods: Twenty-four adult male Swiss mice (SWR/J) weighing 18–25 g were divided into four groups: control, 0.25 mg/kg LPS, 0.50 mg/kg LPS, and 0.75 mg/kg LPS. All groups were treated with LPS or vehicle for 7 days. Behavioral tests were started (Morris water maze for 6 days and Y maze for 1 day) on the last 2 days of injections. After the behavioral procedures, tissues were collected for further histological investigations. Result: All LPS doses induced significant short- and long-term spatial memory impairment in both the Y maze and Morris water maze compared with the control group. Furthermore, histological examination of the hippocampus indicated degenerating neurons in both the 0.50 mg/kg and 0.75 mg/kg LPS groups, while the 0.25 mg/kg LPS group showed less degeneration. Conclusion: our results showed that 0.75 mg/kg LPS had a greater impact on early-stage spatial learning memory and short-term memory than other doses. Our behavioral and histological findings suggest 0.75 mg/kg LPS as a promising dose for LPS-induced AD models

Biochanin A Improves Memory Decline and Brain Pathology in Cuprizone-Induced Mouse Model of Multiple Sclerosis

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system characterized by the demyelination of nerves, neural degeneration, and axonal loss. Cognitive impairment, including memory decline, is a significant feature in MS affecting up to 70% of patients. Thereby, it substantially impacts patients’ quality of life. Biochanin A (BCA) is an o-methylated isoflavone with a wide variety of pharmacological activities, including antioxidant, anti-inflammatory, and neuroprotective activities. Thus, this study aimed to investigate the possible protective effects of BCA on memory decline in the cuprizone (CPZ) model of MS. Thirty Swiss albino male mice (SWR/J) were randomly divided into three groups (n = 10): control (normal chow + i.p. 1:9 mixture of DMSO and PBS), CPZ (0.2% w/w of CPZ mixed into chow + i.p. 1:9 mixture of DMSO and PBS), and CPZ + BCA (0.2% w/w of CPZ mixed into chow + i.p. 40 mg/kg of BCA). At the last week of the study (week 5), a series of behavioral tasks were performed. A grip strength test was performed to assess muscle weakness while Y-maze, novel object recognition task (NORT), and novel arm discrimination task (NADT) were performed to assess memory. Additionally, histological examination of the hippocampus and the prefrontal cortex (PFC) were conducted. BCA administration caused a significant increase in the grip strength compared with the CPZ group. Additionally, BCA significantly improved the mice’s spatial memory in the Y-maze and recognition memory in the NORT and the NADT compared with the CPZ group. Moreover, BCA mitigated neuronal damage in the PFC and the hippocampus after five weeks of administration. In conclusion, our data demonstrates the possible protective effect of BCA against memory deterioration in mice fed with CPZ for five weeks