Sarah Caughey

Changes in the Intensity of Maternal Aggression and Central Oxytocin and Vasopressin V1a Receptors Across the Peripartum Period in the Rat

Maternal aggressive behaviour, which protects the offspring from harm, is one component of maternal behaviour. Not only maternal aggression, but also maternal care and social behaviour in general, is regulated by the brain oxytocin (OXT) and vasopressin (AVP) systems. In the present study, we quantified the intensity of maternal aggression using the maternal defence test at key time points throughout pregnancy, parturition and lactation. Furthermore, we quantified changes in central OXT and arginine AVP V1a receptor (V1a‐R) binding in brain regions known to be important in regulating maternal aggression, aiming to investigate whether central changes coincide with the intensity of this behaviour. The intensity of aggression was found to dramatically change over the peripartum period, with its first appearance on the day before parturition. Aggression intensity fell immediately after parturition, although it increased during days 4–7 of lactation, before almost disappearing at weaning. OXT receptor (OTR) and V1a‐R binding also showed changes through the peripartum period. OTR binding was highest at parturition within the bed nucleus of the stria terminalis and medial preoptic area and on days 4–7 of lactation in the lateral septum (LS) compared to any other time point during the peripartum period. OTR binding positively correlated with the peak of maternal aggression, suggesting that OXT may act in the LS to facilitate the expression of aggressive behaviour. At parturition, V1a‐R binding was at its highest levels in the paraventricular nucleus and central amygdala (CeA) and, in the LS, V1a‐R binding positively correlated with aggressive behaviour. V1a‐R mRNA expression was also increased within the CeA at parturition. Taken together, the observed fluctuations in OTR and V1a‐R binding in the neural circuitry important for regulating maternal behaviour may ensure that maternal aggression is expressed at the correct time during the peripartum period.

Short-term inhibition of 11β-hydroxysteroid dehydrogenase type 1 reversibly improves spatial memory but persistently impairs contextual fear memory in aged mice

High glucocorticoid levels induced by stress enhance the memory of fearful events and may contribute to the development of anxiety and posttraumatic stress disorder. In contrast, elevated glucocorticoids associated with ageing impair spatial memory. We have previously shown that pharmacological inhibition of the intracellular glucocorticoid-amplifying enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) improves spatial memory in aged mice. However, it is not known whether inhibition of 11β-HSD1 will have any beneficial effects on contextual fear memories in aged mice. Here, we examined the effects of UE2316, a selective 11β-HSD1 inhibitor which accesses the brain, on both spatial and contextual fear memories in aged mice using a vehicle-controlled crossover study design. Short-term UE2316 treatment improved spatial memory in aged mice, an effect which was reversed when UE2316 was substituted with vehicle. In contrast, contextual fear memory induced by foot-shock conditioning was significantly reduced by UE2316 in a non-reversible manner. When the order of treatment was reversed following extinction of the original fear memory, and a second foot-shock conditioning was given in a novel context, UE2316 treated aged mice (previously on vehicle) now showed increased fear memory compared to vehicle-treated aged mice (previously on UE2316). Renewal of the original extinguished fear memory triggered by exposure to a new environmental context may explain these effects. Thus 11β-HSD1 inhibition reverses spatial memory impairments with ageing while reducing the strength and persistence of new contextual fear memories. Potentially this could help prevent anxiety-related disorders in vulnerable elderly individuals.

Hypertension Fails to Disrupt White Matter Integrity in Young Or Aged Fisher (F44) Cyp1a1Ren2 Transgenic Rats

Hypertension is linked with an increased risk of white matter hyperintensities; however, recent findings have questioned this association. We examined whether hypertension and additional cerebrovascular risk factors impacted on white matter integrity in an inducible hypertensive rat. No white matter hyperintensities were observed on magnetic resonance imaging either alone or in conjunction with ageing and high-fat diet. Aged hypertensive rats that were fed a high-fat diet had moderately reduced fractional anisotropy in the corpus callosum with no overt pathological features. Herein we show that moderate hypertension alone or with additional risk factors has minimal impact on white matter integrity in this model.

Forebrain-Specific Transgene Rescue of 11β-HSD1 Associates with Impaired Spatial Memory and Reduced Hippocampal Brain-Derived Neurotrophic Factor mRNA Levels in Aged 11β-HSD1 Deficient Mice

Mice lacking the intracellular glucocorticoid‐regenerating enzyme 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) are protected from age‐related spatial memory deficits. 11β‐HSD1 is expressed predominantly in the brain, liver and adipose tissue. Reduced glucocorticoid levels in the brain in the absence of 11β‐HSD1 may underlie the improved memory in aged 11β‐HSD1 deficient mice. However, the improved glucose tolerance, insulin sensitisation and cardioprotective lipid profile associated with reduced peripheral glucocorticoid regeneration may potentially contribute to the cognitive phenotype of aged 11β‐HSD1 deficient mice. In the present study, transgenic mice with forebrain‐specific overexpression of 11β‐HSD1 (Tg) were intercrossed with global 11β‐HSD1 knockout mice (HSD1KO) to examine the influence of forebrain and peripheral 11β‐HSD1 activity on spatial memory in aged mice. Transgene‐mediated delivery of 11β‐HSD1 to the hippocampus and cortex of aged HSD1KO mice reversed the improved spatial memory retention in the Y‐maze but not spatial learning in the watermaze. Brain‐derived neurotrophic factor (BDNF) mRNA levels in the hippocampus of aged HSD1KO mice were increased compared to aged wild‐type mice. Rescue of forebrain 11β‐HSD1 reduced BDNF mRNA in aged HSD1KO mice to levels comparable to aged wild‐type mice. These findings indicate that 11β‐HSD1 regenerated glucocorticoids in the forebrain and decreased levels of BDNF mRNA in the hippocampus play a role in spatial memory deficits in aged wild‐type mice, although 11β‐HSD1 activity in peripheral tissues may also contribute to spatial learning impairments in aged mice.

Pancreatic PYY but not PPY expression is responsive to short-term nutritional state and the pancreas constitutes the major site of PYY mRNA expression in chickens

Highlights • Chicken and quail PYY mRNA sequences evidenced.• Pancreas identified as the major site of PYY mRNA expression in chickens.• Peak of intestinal expression evidenced around the distal jejunum.• Ontogenic development of gradient pancreatic expression of chicken PYY and PPY reported.• Chicken pancreatic PYY shown to increase in response to short-term nutritional state.