Adult hippocampal neurogenesis shapes adaptation and improves stress response: a mechanistic and integrative perspective.

Adult hippocampal neurogenesis (AHN) represents a remarkable form of neuroplasticity that has increasingly been linked to the stress response in recent years. However, the hippocampus does not itself support the expression of the different dimensions of the stress response. Moreover, the main hippocampal functions are essentially preserved under AHN depletion and adult-born immature neurons (abGNs) have no extrahippocampal projections, which questions the mechanisms by which abGNs influence functions supported by brain areas far from the hippocampus. Within this framework, we propose that through its computational influences AHN is pivotal in shaping adaption to environmental demands, underlying its role in stress response. The hippocampus with its high input convergence and output divergence represents a computational hub, ideally positioned in the brain (1) to detect cues and contexts linked to past, current and predicted stressful experiences, and (2) to supervise the expression of the stress response at the cognitive, affective, behavioral, and physiological levels. AHN appears to bias hippocampal computations toward enhanced conjunctive encoding and pattern separation, promoting contextual discrimination and cognitive flexibility, reducing proactive interference and generalization of stressful experiences to safe contexts. These effects result in gating downstream brain areas with more accurate and contextualized information, enabling the different dimensions of the stress response to be more appropriately set with specific contexts. Here, we first provide an integrative perspective of the functional involvement of AHN in the hippocampus and a phenomenological overview of the stress response. We then examine the mechanistic underpinning of the role of AHN in the stress response and describe its potential implications in the different dimensions accompanying this response.

Comparison of endogenous loss and maintenance need for minerals in rainbow trout (Oncorhynchus mykiss) fed fishmeal or plant ingredient-based diets.

Mineral needs as affected by changes in dietary protein and oil sources were studied in rainbow trout. Duplicate groups (n = 30 fish per replicate) of rainbow trout (initial BW: 37 g) were fed either a fish meal/fish oil-based (M) or a complete plant ingredient (V)-based diet at four graded ration (R) levels [apparent satiation (AS), R75, R50 and R25 % of AS]; one treatment group was maintained under starvation. The feeding trial lasted 12 weeks at a water temperature of 17 °C. Dietary intake, apparent digestibility and initial and final whole-body composition data were used to calculate mineral gain which was regressed against digestible mineral intake (both expressed as mg or µg kg(-0.8) day(-1)). Starvation loss (SL), endogenous loss of fed fish (ELF, y-intercept at x = 0) and point of intake for zero balance (PZB, x-intercept at y = 0) were used as estimates of maintenance requirements. SL provided the lowest estimate, ELF provided the net requirement of a mineral for maintenance and PZB provided the digestible dietary intake required to meet maintenance (SL < ELF < PZB). Dietary ingredient composition did not significantly affect the digestible mineral supply required for maintenance (PZB) for any of the minerals (P, Mg, K, Cu and Zn) studied. However, ELF of micro-minerals such as Cu and Zn were significantly affected. The ELF of Cu was significantly lower and that of Zn was significantly higher in V group compared with M-fed fish. Further studies on the effects of such changes in dietary formulations on micro-mineral metabolism are warranted.

Antidepressants recruit new neurons to improve stress response regulation.

Recent research suggests an involvement of hippocampal neurogenesis in behavioral effects of antidepressants. However, the precise mechanisms through which newborn granule neurons might influence the antidepressant response remain elusive. Here, we demonstrate that unpredictable chronic mild stress in mice not only reduces hippocampal neurogenesis, but also dampens the relationship between hippocampus and the main stress hormone system, the hypothalamo-pituitary-adrenal (HPA) axis. Moreover, this relationship is restored by treatment with the antidepressant fluoxetine, in a neurogenesis-dependent manner. Specifically, chronic stress severely impairs HPA axis activity, the ability of hippocampus to modulate downstream brain areas involved in the stress response, the sensitivity of the hippocampal granule cell network to novelty/glucocorticoid effects and the hippocampus-dependent negative feedback of the HPA axis. Remarkably, we revealed that, although ablation of hippocampal neurogenesis alone does not impair HPA axis activity, the ability of fluoxetine to restore hippocampal regulation of the HPA axis under chronic stress conditions, occurs only in the presence of an intact neurogenic niche. These findings provide a mechanistic framework for understanding how adult-generated new neurons influence the response to antidepressants. We suggest that newly generated neurons may facilitate stress integration and that, during chronic stress or depression, enhancing neurogenesis enables a dysfunctional hippocampus to restore the central control on stress response systems, then allowing recovery.

Neuropeptides in psychiatric diseases: an overview with a particular focus on depression and anxiety disorders.

This paper aimed at reviewing the involvement of neuropeptides in various psychiatric diseases, particularly in depression, and anxiety disorders. General features of neuropeptides are first described, including the history of their discovery, their definition, classification, biosynthesis, transport, release, inactivation, as well as their interaction with specific neuronal receptors. The differences with classical neurotransmitters are mentioned, as well as the different patterns of co-transmission. Finally, different mechanisms, both at the cellular and at the systemic level, are proposed that may explain the involvement of these molecules in various psychiatric diseases. Indeed, at the cellular level, a neuropeptide can be involved in a psychiatric disease, either because it is co-localized with a classical neurotransmitter involved in a disease, or because the neuropeptide-containing neuron projects on a target neuron involved in the disease. At the systemic level, a neuropeptide can play a direct role in the expression of a symptom of the disease. This is illustrated by different examples.