The impact of maternal separation on adult mouse behaviour and on the total neuron number in the mouse hippocampus

The maternal separation paradigm has been applied to C57BL/6J mice as an animal developmental model for understanding structural deficits leading to abnormal behaviour. A maternal separation (MS) model was used on postnatal day (PND) 9, where the pups were removed from their mother for 24 h (MS24). When the pups were 10 weeks old, the level of anxiety and fear was measured with two behavioural tests; an open field test and an elevated plus maze test. The Barnes platform maze was used to test spatial learning, and memory by using acquisition trials followed by reverse trial sessions. The MS24 mice spent more time in the open arms of the elevated plus maze compared to controls, but no other treatment differences were found in the emotional behavioural tests. However, in the reverse trial for the Barnes maze test there was a significant difference in the frequency of visits to the old goal, the number of errors made by the MS24 mice compared to controls and in total distance moved. The mice were subsequently sacrificed and the total number of neurons estimated in the hippocampus using the optical fractionator. We found a significant loss of neurons in the dentate gyrus in MS mice compared to controls. Apparently a single maternal separation can impact the number of neurons in mouse hippocampus either by a decrease of neurogenesis or as an increase in neuron apoptosis. This study is the first to assess the result of maternal separation combining behaviour and stereology

Bi-Directional Effect of Cholecystokinin Receptor-2 Overexpression on Stress-Triggered Fear Memory and Anxiety in the Mouse

Fear, an emotional response of animals to environmental stress/threats, plays an important role in initiating and driving adaptive response, by which the homeostasis in the body is maintained. Overwhelming/uncontrollable fear, however, represents a core symptom of anxiety disorders, and may disturb the homeostasis. Because to recall or imagine certain cue(s) of stress/threats is a compulsory inducer for the expression of anxiety, it is generally believed that the pathogenesis of anxiety is associated with higher attention (acquisition) selectively to stress or mal-enhanced fear memory, despite that the actual relationship between fear memory and anxiety is not yet really established. In this study, inducible forebrain-specific cholecystokinin receptor-2 transgenic (IF-CCKR-2 tg) mice, different stress paradigms, batteries of behavioral tests, and biochemical assays were used to evaluate how different CCKergic activities drive fear behavior and hormonal reaction in response to stresses with different intensities. We found that in IF-CCKR-2 tg mice, contextual fear was impaired following 1 trial of footshock, while overall fear behavior was enhanced following 36 trials of footshock, compared to their littermate controls. In contrast to a standard Yerkes-Dodson (inverted-U shaped) stress-fear relationship in control mice, a linearized stress-fear curve was observed in CCKR-2 tg mice following gradient stresses. Moreover, compared to 1 trial, 36 trials of footshock in these transgenic mice enhanced anxiety-like behavior in other behavioral tests, impaired spatial and recognition memories, and prolonged the activation of adrenocorticotropic hormone (ACTH) and glucocorticoids (CORT) following new acute stress. Taken together, these results indicate that stress may trigger two distinctive neurobehavioral systems, depending on both of the intensity of stress and the CCKergic tone in the brain. A “threshold theory” for this two-behavior system has been suggested

Neonatal cerebrovascular autoregulation.

Cerebrovascular pressure autoregulation is the physiologic mechanism that holds cerebral blood flow (CBF) relatively constant across changes in cerebral perfusion pressure (CPP). Cerebral vasoreactivity refers to the vasoconstriction and vasodilation that occur during fluctuations in arterial blood pressure (ABP) to maintain autoregulation. These are vital protective mechanisms of the brain. Impairments in pressure autoregulation increase the risk of brain injury and persistent neurologic disability. Autoregulation may be impaired during various neonatal disease states including prematurity, hypoxic-ischemic encephalopathy (HIE), intraventricular hemorrhage, congenital cardiac disease, and infants requiring extracorporeal membrane oxygenation (ECMO). Because infants are exquisitely sensitive to changes in cerebral blood flow (CBF), both hypoperfusion and hyperperfusion can cause significant neurologic injury. We will review neonatal pressure autoregulation and autoregulation monitoring techniques with a focus on brain protection. Current clinical therapies have failed to fully prevent permanent brain injuries in neonates. Adjuvant treatments that support and optimize autoregulation may improve neurologic outcomes