Desacyl Ghrelin Decreases Anxiety-like Behavior in Male Mice.

Ghrelin is a 28-amino acid polypeptide that regulates feeding, glucose metabolism, and emotionality (stress, anxiety, and depression). Plasma ghrelin circulates as desacyl ghrelin (DAG) or, in an acylated form, acyl ghrelin (AG), through the actions of ghrelin O-acyltransferase (GOAT), exhibiting low or high affinity, respectively, for the growth hormone secretagogue receptor (GHSR) 1a. We investigated the role of endogenous AG, DAG, and GHSR1a signaling on anxiety and stress responses using ghrelin knockout (Ghr KO), GOAT KO, and Ghsr stop-floxed (Ghsr null) mice. Behavioral and hormonal responses were tested in the elevated plus maze and light/dark (LD) box. Mice lacking both AG and DAG (Ghr KO) increased anxiety-like behaviors across tests, whereas anxiety reactions were attenuated in DAG-treated Ghr KO mice and in mice lacking AG (GOAT KO). Notably, loss of GHSR1a (Ghsr null) did not affect anxiety-like behavior in any test. Administration of AG and DAG to Ghr KO mice with lifelong ghrelin deficiency reduced anxiety-like behavior and decreased phospho-extracellular signal-regulated kinase phosphorylation in the Edinger-Westphal nucleus in wild-type mice, a site normally expressing GHSR1a and involved in stress- and anxiety-related behavior. Collectively, our data demonstrate distinct roles for endogenous AG and DAG in regulation of anxiety responses and suggest that the behavioral impact of ghrelin may be context dependent.

Development of the human oculomotor nuclear complex: Centrally-projecting Edinger-Westphal nucleus.

BACKGROUND: The cytoarchitecturally defined Edinger-Westphal nucleus (EW) is now referred to by many investigators as the centrally-projecting EW (EWcp) in humans. Although the mature structure is well-characterized, there have been few reports describing the precise morphology of this nucleus during the second half of gestation. SUBJECTS/DESIGN: Eleven brains were examined from preterm infants, aged 20-39 postmenstrual weeks, who died of various causes. After fixation, the brains were embedded in celloidin and serial sections of 30-µm thickness were cut in the horizontal plane. Sections were stained using the Klüver-Barrera method. In addition to microscopic observations, computerized 3D reconstruction and morphometry were performed. RESULTS: From 21 weeks, the EWcp had a distinctive, complex 3D structure comprising two or three parts. The dorsal part was arcuate, half encircling the oculomotor somatic nuclei (OSN). The rostral part was the most voluminous, ventral to the rostral OSN, extending anteriorly. The caudal part was the smallest, and was composed of several neuronal groups near the ventral tip of the OSN. In three cases, the caudal part was absent. It could also be joined to the rostral part, forming a ventral part. The total volume of the EWcp increased exponentially with age, and the ventral part grew more rapidly than the dorsal part. The mean neuronal profile area increased linearly with age, and the rate of increase was almost equal between the dorsal and ventral parts. CONCLUSIONS: This study suggests that a distinctive, complex, two- or three-part 3D structure of the EWcp is preserved after mid-gestation, and that the ventral part of the EWcp may expand in volume more rapidly than the dorsal part.

Ophthalmology issues in schizophrenia.

Schizophrenia is a complex mental disorder associated with not only cognitive dysfunctions, such as memory and attention deficits, but also changes in basic sensory processing. Although most studies on schizophrenia have focused on disturbances in higher-order brain functions associated with the prefrontal cortex or frontal cortex, recent investigations have also reported abnormalities in low-level sensory processes, such as the visual system. At very early stages of the disease, schizophrenia patients frequently describe in detail symptoms of a disturbance in various aspects of visual perception that may lead to worse clinical symptoms and decrease in quality of life. Therefore, the aim of this review is to describe the various studies that have explored the visual issues in schizophrenia.

Dendritic and spinal alterations of neurons from Edinger-Westphal nucleus in Alzheimer's disease.

Alzheimer's disease (AD) is a heterogeneous neurodegenerative disorder, causing a progressive decline of intellectual faculties, impairment of behavior and social performance, and impairment of speech eloquence, associated with various neurological manifestations based on a variable neuropathological background. Edinger-Westphal nucleus is a selective target of Alzheimer pathology early in the course of the disease. We attempted to determine the morphological alterations of the dendrites and the dendritic spines in Edinger-Westphal nucleus of 7 cases that fulfilled the diagnostic criteria for Alzheimer's disease. For the histological study, we applied (a) routine neuropathological techniques and (b) rapid Golgi method. We proceeded to 3D neuronal reconstruction for the estimation of dendritic and spinal changes in Alzheimer's disease. The morphological and morphometric analysis revealed a substantial neuronal loss and synaptic alterations in Edinger-Westphal nucleus in all the cases of Alzheimer's disease. Distal dendritic branches are prominently affected. The neuronal loss and alteration of the spines in Edinger-Westphal nucleus in Alzheimer's disease may be related to the exaggerated pupillary reaction to cholinergic antagonists. Furthermore, the vulnerability of distal branches to Alzheimer's disease might be related to neuroplasticity impairment.