Hypothalamic Diseases

Is the Cerebellum Involved in the Nervous Control of the Immune System Function?

Background: According to the views of psychoneuroendocrinoimmunology, many interactions exist between nervous, endocrine and immune system the purpose of which is to achieve adaptive measures restoring an internal equilibrium (homeostasis) following stress conditions. The center where these interactions converge is the hypothalamus. This is a center of the autonomic nervous system that controls the visceral systems, including the immune system, through both the nervous and neuroendocrine mechanisms. The nervous mechanisms are based on nervous circuits that bidirectionally connect hypothalamic neurons and neurons of the sympathetic and parasympathetic system; the neuroendocrine mechanisms are based on the release by neurosecretory hypothalamic neurons of hormones that target the endocrine cells and on the feedback effects of the hormones secreted by these endocrine cells on the same hypothalamic neurons. Moreover, the hypothalamus is an important subcortical center of the limbic system that controls through nervous and neuroendocrine mechanisms the areas of the cerebral cortex where the psychic functions controlling mood, emotions, anxiety and instinctive behaviors take place. Accordingly, various studies conducted in the last decades have indicated that hypothalamic diseases may be associated with immune and/or psychic disorders.

Objective: Various researches have reported that the hypothalamus is controlled by the cerebellum through a feedback nervous circuit, namely the hypothalamocerebellar circuit, which bi-directionally connects regions of the hypothalamus, including the immunoregulatory ones, and related regions of the cerebellum. An objective of the present review was to analyze the anatomical bases of the nervous and neuroendocrine mechanisms for the control of the immune system and, in particular, of the interaction between hypothalamus and cerebellum to achieve the immunoregulatory function.

Conclusion: Since the hypothalamus represents the link through which the immune functions may influence the psychic functions and vice versa, the cerebellum, controlling several regions of the hypothalamus, could be considered as a primary player in the regulation of the multiple functional interactions postulated by psychoneuroendocrinoimmunology.

Metabolic Dysfunction in Alzheimers Disease and Related Neurodegenerative Disorders

Alzheimers disease and other related neurodegenerative diseases are highly debilitating disorders that affect millions of people worldwide. Efforts towards developing effective treatments for these disorders have shown limited efficacy at best, with no true cure to this day being present. Recent work, both clinical and experimental, indicates that many neurodegenerative disorders often display a coexisting metabolic dysfunction which may exacerbate neurological symptoms. It stands to reason therefore that metabolic pathways may themselves contain promising therapeutic targets for major neurodegenerative diseases. In this review, we provide an overview of some of the most recent evidence for metabolic dysregulation in Alzheimers disease, Huntingtons disease, and Parkinsons disease, and discuss several potential mechanisms that may underlie the potential relationships between metabolic dysfunction and etiology of nervous system degeneration. We also highlight some prominent signaling pathways involved in the link between peripheral metabolism and the central nervous system that are potential targets for future therapies, and we will review some of the clinical progress in this field. It is likely that in the near future, therapeutics with combinatorial neuroprotective and ‘eumetabolic’ activities may possess superior efficacies compared to less pluripotent remedies.

Somatostatin: A Hormone for the Heart?

Somatostatin (somatotropin release inhibitory factor; SRIF) peptides are widely distributed throughout the mammalian body and act through a family of genetically distinct, guanine nucleotide regulatory protein coupled (Gprotein- coupled), cell surface receptors (sst1-5). Compelling evidence shows that SRIF and SRIF peptidyl analogs modulate vascular function, with actions upon smooth muscle and endothelium. SRIF receptors are known to exist in the carotid endothelium, a principal target for the pro-inflammatory cascade that accompanies coronary artery disease. SRIF- 14 and SRIF analogs are anti-inflammatory but the molecular mechanism involved remains unclear. Since crucial steps in the endothelial inflammation response include endothelial activation by cytokines, adhesion molecule expression and cellmonocyte interactions, peptide agents that inhibit these steps might provide a novel strategy for reducing vascular inflammation. SRIF, acting through its cognate receptors, modulates a variety of intracellular effectors that are linked to inflammation including phosphotyrosine phosphatases, the extracellular regulated protein kinase 1 and 2 (ERK1/2) cascade, adenylyl cyclase and endothelial nitric oxide synthase. Directly or indirectly, SRIF also functions to inhibit endothelial cell proliferation and induce apoptosis. A detailed understanding of SRIF actions could provide a rational basis for using SRIF ligands in controlling vascular inflammation and inhibiting cytokine signaling, critical events in atherogenesis.