Learning and memory impairments in a neuroendocrine mouse model of anxiety/depression

Abstract

Cognitive disturbances are often reported as serious incapacitating symptoms by patients suffering from major depressive disorders (MDDs). Such deficits have been observed in various animal models based on environmental stress. Here, we performed a complete characterization of cognitive functions in a neuroendocrine mouse model of depression based on a chronic (4 weeks) corticosterone administration (CORT). Cognitive performances were assessed using behavioral tests measuring episodic (novel object recognition test, NORT), associative (one-trial contextual fear conditioning, CFC), and visuo-spatial (Morris water maze, MWM; Barnes maze, BM) learning/memory. Altered emotional phenotype after chronic corticosterone treatment was confirmed in mice using tests predictive of anxiety or depression-related behaviors. In the NORT, CORT-treated mice showed a decrease in time exploring the novel object during the test session and a lower discrimination index compared to control mice, characteristic of recognition memory impairment. Associative memory was also impaired, as observed with a decrease in freezing duration in CORT-treated mice in the CFC, thus pointing out the cognitive alterations in this model. In the MWM and in the BM, spatial learning performance but also short-term spatial memory were altered in CORT-treated mice. In the MWM, unlike control animals, CORT-treated animals failed to learn a new location during the reversal phase, suggesting a loss of cognitive flexibility. Finally, in the BM, the lack of preference for the target quadrant during the recall probe trial in animals receiving corticosterone regimen demonstrates that long-term retention was also affected in this paradigm. Taken together, our results highlight that CORT-induced anxio-depressive-like phenotype is associated with a cognitive deficit affecting all aspects of memory tested.

Protective effect of the orientin on noise-induced cognitive impairments in mice

“…Many studies have reported that elevated corticosterone concentrations contributed to stress-induced impairments in cognitive and learning abilities [8]. In our study, the serum corticosterone level was markedly increased after noise exposure, while treatment with orientin markedly decreased the serum corticosterone level.…”

“…In a continuously open auditory system, noise-induced stress can cause the significant release of hypothalamic hormones such as the corticotrophin-releasing hormone and the adrenocorticotropic hormone, which increase the activity of the HPA-axis and the release of corticosterone from the adrenal cortex [7]. It is known that high levels of corticosterone, induced by the hyperactivity of the HPA axis, impair cognition, including learning, memory, and spatial recognition [8].…”

A Double-Blind, R CT Testing Beneficial Modulation of B DNF in Middle-Aged, Life Style-Stressed Subjects: A Clue to Brain Protection?

“…Indeed the hippocampus is a main structure for spatial learning and memory and, together with the amygdala and prefrontal cortex [22] and is susceptible to stress and senescence when glucocorticoid injury produces dendritic remodeling of CA3 pyramidal neurons and a decrement in adult neurogenesis in the dentate gyrus [23]. Moreover, these alterations are related also to emotional response impairments [21] and stress represents also the major precipitating factor in mood disorders.…”

Neurochemical correlation between major depressive disorder and neurodegenerative diseases

“…Furthermore, studies in late-life depression have demonstrated a reduction in hippocampal volume in the depressed elderly population [167][168]. Studies with animal models have also shown that these structural abnormalities in the hippocampus or cortex are associated with cognitive deficits in memory and decision-making, as well as depression [169][170][171].…”