The effect of high fat, high sugar, and combined high fat-high sugar diets on spatial learning and memory in rodents: A meta-analysis

Influence of endogenous and exogenous growth factors on choline-acetyltransferase (ChAT) activity in rats with fimbria-fornix lesions and acetylcholine-rich transplants in the hippocampus

The effects of intrahippocampal raphe and/or septal grafts in rats with fimbria-fornix lesions depend on the origin of the grafted tissue and the behavioural task used

The radial arm maze (RAM) is a common behavioral test to quantify spatial learning and memory in rodents. Prior attempts to refine the standard experimental setup have been insufficient. Previously, we demonstrated the feasibility of a fully automated, voluntary, and stress-free eight-arm RAM not requiring food or water deprivation. Here, we compared this newly developed refined RAM to a classic manual experimental setup using 24 female 10–12 weeks old C57BL/6J mice. We used a lipopolysaccharide (LPS)-induced model of systemic inflammation to examine long-term cognitive impairment for up to 13 weeks following LPS injection. Both mazes demonstrated robust spatial learning performance during the working memory paradigm. The refined RAM detected spatial learning and memory deficits among LPS-treated mice in the working memory paradigm, whereas the classic RAM detected spatial learning and memory deficits only in the combined working/reference memory paradigm. In addition, the refined RAM allowed for quantification of an animal’s overall exploratory behavior and day/night activity pattern. While our study highlights important aspects of refinement of the new setup, our comparison of methods suggests that both RAMs have their respective merits depending on experimental requirements.

Apolipoprotein E4 (apoE4) allele is the major genetic risk factor for sporadic Alzheimer disease (AD) due to the higher prevalence and earlier onset of AD in apoE4 carriers. Accumulating data suggest that the interaction between the N- and the C-terminal domains in the protein may be the main pathologic feature of apoE4. To test this hypothesis, we used Arg-61 mice, a model of apoE4 domain interaction, by introducing the domain interaction feature of human apoE4 into native mouse apoE. We carried out hippocampus-dependent learning and memory tests and related cellular and molecular assays on 12- and 3-month-old Arg-61 and age-matched background C57BL/6J mice. Learning and memory task performance were impaired in Arg-61 mice at both old and young ages compared with C57BL/6J mice. Surprisingly, young Arg-61 mice had more mitotic doublecortin-positive cells in the subgranular zone; mRNA levels of brain-derived neurotrophic factor (BDNF) and TrkB were also higher in 3-month-old Arg-61 hippocampus compared with C57BL/6J mice. These early-age neurotrophic and neurogenic (proliferative) effects in the Arg-61 mouse may be an inadequate compensatory but eventually detrimental attempt by the system to "repair" itself. This is supported by the higher cleaved caspase-3 levels in the young animals that not only persisted, but increased in old age, and the lower levels of doublecortin at old age in the hippocampus of Arg-61 mice. These results are consistent with human apoE4-dependent cognitive and neuro-pathologic changes, supporting the principal role of domain interaction in the pathologic effect of apoE4. Domain interaction is, therefore, a viable therapeutic/prophylactic target for cognitive impairment and AD in apoE4 subjects.

Despite recognition of stress as a causation of severe neuropsychological dysfunctions, no casual and clinically effective anti-stress therapeutic strategy has yet been found. We have previously shown that blockade of initial stress response by angiotensin receptor blockers alleviates the negative effect of prolonged stress on cognitive non-spatial functions of rats. Here we aimed to find whether telmisartan reduces stress-related memory decline in spatial hippocampal-dependent learning tasks conditioned upon differences in level of stress induced by aversive nature of memory tests. Male Wistar rats were exposed to chronic restraint stress for three weeks and daily treated with either vehicle or telmisartan (1 mg/kg). Afterwards rats were tested in three spatial learning and memory paradigms: Morris water maze (MWM), radial arm maze (RAM), and Barnes maze (BM). Stressed animals demonstrated significantly impaired performance in all the tests, which was normalized in the animals stressed and treated with telmisartan. Interestingly, despite the fact that MWM and RAM are more stressful, which affects animal behavior, therefore considered less sensitive than BM, more significant effect of telmisartan was found in MWM and RAM than BM. AT1 angiotensin receptor blockade attenuates negative effect of both acute and chronic stress on spatial memory.

Willughbeia cochinchinensis prevents scopolamine-induced deficits in memory, spatial learning, and object recognition in rodents

Preferential enhancement of working memory in mice lacking adenosine A2A receptors

Negative effects of chronic oral chlorpromazine and olanzapine treatment on the performance of tasks designed to assess spatial learning and working memory in rats

Stress impairs performance in spatial water maze learning tasks

A male advantage for spatial learning and memory tasks is well documented among humans and rodents. A possible physiological cause for this male advantage is activational effects of androgens among males. The spatial memory of eight castrated and eight sham-castrated adult male rats was compared using a working-reference memory version of the eight-arm radial arm maze followed by a reference memory version of the Morris water maze. After maze testing, blood was collected from each rat, and testosterone levels were determined using radioimmunoassay. In the radial arm maze, castrates committed significantly more working memory errors and significantly fewer reference memory errors than did shams. In the water maze, no statistically significant differences were found for acquisition or retention. There was a trend for shams with higher testosterone levels to have better retention in the water maze, but this seemed to be due to higher levels of perseverance rather than better reference memory. Castration may have affected performance in the radial arm maze and not in the water maze because the radial arm maze was a more difficult task or because the water maze was aversively motivated while the radial arm maze was appetitively motivated. Our results indicate that androgens improve working memory and may impair reference memory, but the effects of androgens on reference memory seem to be task dependent.

Mammillary bodies and the mammillothalamic tract are parts of a classic neural circuitry that has been implicated in severe memory disturbances accompanying Korsakoff's syndrome. However, the specific role of mammillary bodies in memory functions remains controversial, often being considered as just an extension of the hippocampal memory system. To study this issue we used mutant mice with a targeted mutation in the transcription factor gene Foxb1. These mice suffer perinatal degeneration of the medial and most of the lateral mammillary nuclei, as well as of the mammillothalamic bundle. Foxb1 mutant mice showed no deficits in such hippocampal-dependent tasks as contextual fear conditioning and social transmission of food preference. They were also not impaired in the spatial reference memory test in the radial arm maze. However, Foxb1 mutants showed deficits in the task for spatial navigation within the Barnes maze. Furthermore, they showed impairments in spatial working memory tasks such as the spontaneous alternation and the working memory test in the radial arm maze. Thus, our behavioural analysis of Foxb1 mutants suggests that the medial mammillary nuclei and mammillothalamic tract play a role in a specific subset of spatial tasks, which require combined use of both spatial and working memory functions. Therefore, the mammillary bodies and the mammillothalamic tract may form an important route through which the working memory circuitry receives spatial information from the hippocampus.

Estrogen and NMDA receptor antagonism: effects upon reference and working memory

Background: Memory impairment involves a decline in cognitive functions such as memory, thinking, behavior, and the ability to perform daily tasks. The complex mechanisms underlying its pathogenesis contribute to the limited effectiveness of current treatments. Prolonged use of existing therapies often leads to reduced efficacy and serious side effects, complicating management. In this context, medicinal plants, particularly Azadirachta indica leaf extract (AILE), have gained attention due to their diverse therapeutic applications and minimal adverse effects. Objective: This study aimed to evaluate the effects of AILE on ketamine-induced memory impairment in male Wistar rats in Morris Water Maze (MWM) and Radial Arm Maze (RAM) tests. Methods: Ethical approval was obtained from the Institutional Review Board (IRB) of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka. This experimental study was carried out in the Department of Physiology, BSMMU. The rats were divided into three groups: Group 1 (G1) normal memory, Group 2 (G2), memory impaired, Group 3 (G3) experimental. Each group was further divided into subgroups based on memory performance tests using the RAM and MWM. Data were expressed as mean±SEM and analyzed using SPSS (version 16). ANOVA with Bonferroni post hoc tests and Student’s paired t-tests were applied, with p ≤ 0.05 considered statistically significant. Results: Ketamine-treated rats demonstrated significantly increased working memory errors (p ≤ 0.001) and reference memory errors (p ≤ 0.001) in the RAM, along with delayed escape latency (p ≤ 0.001) and fewer target crossings (p ≤ 0.001) in the MWM compared to normal rats. Pretreatment with AILE significantly reduced working memory errors (p ≤ 0.001) and reference memory errors (p ≤ 0.001) in the RAM and improved escape latency (p ≤ 0.001) and target crossings (p ≤ 0.001) in the MWM relative to ketamine-treated rats. Notably, memory performance variables in AILE-pretreated rats were comparable to normal rats, except for a significantly higher frequency of target crossings (p ≤ 0.05) in the MWM. Conclusion: The results suggested that ketamine significantly impairs spatial learning and memory, as indicated by increased errors in the RAM and poorer performance in the MWM. However, pretreatment with AILE effectively mitigates these cognitive deficits, restoring memory performance to levels comparable to normal rats. Interestingly, AILE-pretreated rats demonstrated even greater target crossings in the MWM than normal rats, suggesting a potential enhancement of spatial memory retrieval. These findings indicate that AILE may have neuroprotective or cognitive-enhancing properties against ketamine-induced memory impairments.

Spatial memory deficits in a virtual reality eight-arm radial maze in schizophrenia

Exposure to nonionizing electromagnetic fields has been reported to affect the functions of the central nervous system. A consequence of functional disturbance in the nervous system is changes in behavior in the animal. Indeed, exposure to radio-frequency electromagnetic radiation (RFR) and extremely low frequency electromagnetic fields has been shown to affect behavioral functions. The following is a brief summary of experiments performed in our laboratory investigating the effects of electromagnetic field exposure on spatial learning and memory functions in the rat. These involve studies using the radial arm maze and the Morris water maze. Both mazes have been used extensively in the study of spatial memory and learning in rodents.