Neuroprotection by leptin in a rat model of permanent cerebral ischemia: effects on STAT3 phosphorylation in discrete cells of the brain

In addition to its effects in the hypothalamus to control body weight, leptin is involved in the regulation of neuronal function, development and survival. Recent findings have highlighted the neuroprotective effects of leptin against ischemic brain injury; however, to date, little is known about the role performed by the signal transducer and activator of transcription (STAT)-3, a major mediator of leptin receptor transduction pathway in the brain, in the beneficial effects of the hormone. Our data demonstrate that systemic acute administration of leptin produces neuroprotection in rats subjected to permanent middle cerebral artery occlusion (MCAo), as revealed by a significant reduction of the brain infarct volume and neurological deficit up to 7 days after the induction of ischemia. By combining a subcellular fractionation approach with immunohistofluorescence, we observe that neuroprotection is associated with a cell type-specific modulation of STAT3 phosphorylation in the ischemic cortex. The early enhancement of nuclear phospho-STAT3 induced by leptin in the astrocytes of the ischemic penumbra may contribute to a beneficial effect of these cells on the evolution of tissue damage. In addition, the elevation of phospho-STAT3 induced by leptin in the neurons after 24 h MCAo is associated with an increased expression of tissue inhibitor of matrix metalloproteinases-1 in the cortex, suggesting its possible involvement to the neuroprotection produced by the adipokine

Characterization of a thy1.2 GFP transgenic mouse reveals a tissue-specific organization of the spinal dorsal horn

In this study, transgenic mice in which membrane-linked enhanced green fluorescent protein (mGFP) is expressed from the Thy1.2 promoter were used. In these mice, a subpopulation of small to medium sized DRG neurons double stained for IB4 but not for CGRP. Most of the peripheral terminals traversed the dermis and ramify within the epidermis and form superficial terminals. Within the spinal cord, these afferents terminated exclusively within the substantia gelatinosa (SG). A second fibre type in the skin also expressed mGFP, and formed club-shaped endings towards the bases of hairs. Injury to the sciatic nerve resulted in mGFP loss from the SG ipsilateral to the nerve injury, but also in the corresponding region contralaterally. Together, these findings reveal the specificity of connectivity of a defined subpopulation of DRG sensory neurons innervating the epidermis and this will facilitate analysis of their physiological functions

The regulation of brain states by neuroactive substances distributed via the cerebrospinal fluid; a review.

Contains fulltext : 83842.pdf (publisher's version ) (Open Access)The cerebrospinal fluid (CSF) system provides nutrients to and removes waste products from the brain. Recent findings suggest, however, that in addition, the CSF contains message molecules in the form of actively released neuroactive substances. The concentrations of these vary between locations, suggesting they are important for the changes in brain activity that underlie different brain states, and induce different sensory input and behavioral output relationships.The cranial CSF displays a rapid caudally-directed ventricular flow followed by a slower rostrally-directed subarachnoid flow (mainly towards the cribriform plate and from there into the nasal lymphatics). Thus, many brain areas are exposed to and can be influenced by substances contained in the CSF. In this review we discuss the production and flow of the CSF, including the mechanisms involved in the regulation of its composition. In addition, the available evidence for the release of neuropeptides and other neuroactive substances into the CSF is reviewed, with particular attention to the selective effects of these on distant downstream receptive brain areas. As a conclusion we suggest that (1) the flowing CSF is involved in more than just nutrient and waste control, but is also used as a broadcasting system consisting of coordinated messages to a variety of nearby and distant brain areas; (2) this special form of volume transmission underlies changes in behavioral states