Abstract:
The neuroendocrine hypothalamus integrates peripheral nutritional and hormonal cues to regulate essential physiological processes, including appetite, metabolism and reproduction. While the mechanisms by which hormones traverse the blood-brain barrier to access the hypothalamic parenchyma are well characterised, how these signals subsequently diffuse and distribute within the brain's extracellular space and matrix remains poorly understood. Emerging evidence implicates specialised components of the extracellular matrix, such as perineuronal nets (PNNs), in modulating hormonal and nutrient bioavailability, as well as neuronal excitability and plasticity. In the hypothalamus, extracellular matrix components are highly dynamic and respond to nutritional and hormonal cues. In preclinical models of metabolic disorders involving the neuroendocrine system - such as obesity and type 2 diabetes - these components undergo maladaptive remodelling. This Review discusses recent advances in our understanding of how the extracellular environment shapes neuroendocrine signalling in the hypothalamus, and explores the broader implications for systemic hormonal regulation and neuroendocrine disease pathophysiology.

Abstract:
Hyperemia in response to neural activity is essential for brain health. A hyperemic response delivers O(2) and nutrients, clears metabolic waste, and concomitantly exposes cerebrovascular endothelial cells to hemodynamic forces. While neurovascular research has primarily centered on the front end of hyperemia-neuronal activity-to-vascular response-the mechanical consequences of hyperemia have gone largely unexplored. Piezo1 is an endothelial mechanosensor that senses hyperemia-associated forces. Using genetic mouse models and pharmacologic approaches to manipulate endothelial Piezo1 function, we evaluated its role in blood flow control and whether it impacts cognition. We provide evidence of a built-in brake system that sculpts hyperemia, and specifically show that Piezo1 activation triggers a mechano-feedback system that promotes blood flow recovery to baseline. Further, genetic Piezo1 modification led to deficits in complementary memory tasks. Collectively, our findings establish a role for endothelial Piezo1 in cerebral blood flow regulation and a role in its behavioral sequelae.

Abstract:
Affective and substance-use disorders are associated with overweight and obesity-related complications, which are often due to the overconsumption of palatable food. Both high-fat diets (HFDs) and psychostimulant drugs modulate the neuro-circuitry regulating emotional processing and metabolic functions. However, it is not known how they interact at the behavioural level, and whether they lead to overlapping changes in neurobiological endpoints. In this literature review, we describe the impact of HFDs on emotionality, cognition, and reward-related behaviour in rodents. We also outline the effects of HFD on brain metabolism and plasticity involving mitochondria. Moreover, the possible overlap of the neurobiological mechanisms produced by HFDs and psychostimulants is discussed. Our in-depth analysis of published results revealed that HFDs have a clear impact on behaviour and underlying brain processes, which are largely dependent on the developmental period. However, apart from the studies investigating maternal exposure to HFDs, most of the published results involve only male rodents. Future research should also examine the biological impact of HFDs in female rodents. Further knowledge about the molecular mechanisms linking stress and obesity is a crucial requirement of translational research and using rodent models can significantly advance the important search for risk-related biomarkers and the development of clinical intervention strategies.