Paolo Govoni

Largely segregated parietofrontal connections linking rostral intraparietal cortex (areas AIP and VIP) and the ventral premotor cortex (areas F5 and F4).

Abstract Two functionally different cortical areas are located in the rostral part of the intraparietal sulcus (IP): the ventral intraparietal area (VIP), along the fundus of the sulcus, and the anterior intraparietal area (AIP), rostral in the lateral bank. VIP and AIP have functional properties comparable to those of the ventral premotor areas, F4 and F5, respectively. The aim of this study was to establish whether these intraparietal and premotor areas have direct and specific anatomical connections. Neural tracers were injected in F4, F5, and AIP in three macaque monkeys. The results showed that F4 and F5 are targets of strong projections from VIP and AIP, respectively, and that the linkage between F5 and AIP is highly selective. These data support the notion that parietofrontal connections selectively link areas displaying similar functional properties and form largely segregated anatomical circuits. Each of these circuits is possibly dedicated to specific aspects of sensorimotor transformations. In particular, the AIP-F5 circuit should play a crucial role in visuomotor transformation for grasping, the VIP-F4 circuit is possibly involved in peripersonal space coding for movement.

Superior Area 6 Afferents From the Superior Parietal Lobule in the Macaque Monkey

Superior area 6 of the macaque monkey frontal cortex is formed by two cytoarchitectonic areas: F2 and F7. In the present experiment, we studied the input from the superior parietal lobule (SPL) to these areas by injecting retrograde neural tracers into restricted parts of F2 and F7. Additional injections of retrograde tracers were made into the spinal cord to define the origin of corticospinal projections from the SPL. The results are as follows: 1) The part of F2 located around the superior precentral dimple (F2 dimple region) receives its main input from areas PEc and PEip (PE intraparietal, the rostral part of area PEa of Pandya and Seltzer, [1982] J. Comp. Neurol. 204:196–210). Area PEip was defined as that part of area PEa that is the source of corticospinal projections. 2) The ventrorostral part of F2 is the target of strong projections from the medial intraparietal area (area MIP) and from the dorsal part of the anterior wall of the parietooccipital sulcus (area V6A). 3) The ventral and caudal parts of F7 receive their main parietal input from the cytoarchitectonic area PGm of the SPL and from the posterior cingulate cortex. 4) The dorsorostral part of F7, which is also known as the supplementary eye field, is not a target of the SPL, but it receives mostly afferents from the inferior parietal lobule and from the temporal cortex. It is concluded that at least three separate parietofrontal circuits link the superior parietal lobule with the superior area 6. Considering the functional properties of the areas that form these circuits, it is proposed that the PEc/PEip‐F2 dimple region circuit is involved in controlling movements on the basis of somatosensory information, which is the traditional role proposed for the whole dorsal premotor cortex. The two remaining circuits appear to be involved in different aspects of visuomotor transformations. J. Comp. Neurol. 402:327–352, 1998.

Metabolic consequences and vulnerability to diet-induced obesity in male mice under chronic social stress.

Social and psychological factors interact with genetic predisposition and dietary habit in determining obesity. However, relatively few pre-clinical studies address the role of psychosocial factors in metabolic disorders. Previous studies from our laboratory demonstrated in male mice: 1) opposite status-dependent effect on body weight gain under chronic psychosocial stress; 2) a reduction in body weight in individually housed (Ind) male mice. In the present study these observations were extended to provide a comprehensive characterization of the metabolic consequences of chronic psychosocial stress and individual housing in adult CD-1 male mice. Results confirmed that in mice fed standard diet, dominant (Dom) and Ind had a negative energy balance while subordinate (Sub) had a positive energy balance. Locomotor activity was depressed in Sub and enhanced in Dom. Hyperphagia emerged for Dom and Sub and hypophagia for Ind. Dom also showed a consistent decrease of visceral fat pads weight as well as increased norepinephrine concentration and smaller adipocytes diameter in the perigonadal fat pad. On the contrary, under high fat diet Sub and, surprisingly, Ind showed higher while Dom showed lower vulnerability to obesity associated with hyperphagia. In conclusion, we demonstrated that social status under chronic stress and individual housing deeply affect mice metabolic functions in different, sometime opposite, directions. Food intake, the hedonic response to palatable food as well as the locomotor activity and the sympathetic activation within the adipose fat pads all represent causal factors explaining the different metabolic alterations observed. Overall this study demonstrates that pre-clinical animal models offer a suitable tool for the investigation of the metabolic consequences of chronic stress exposure and associated psychopathologies.

The analysis of chromatin organisation allows selection of mouse antral oocytes competent for development to blastocyst.

Mouse antral oocytes can be classified in two different types termed SN or NSN oocytes, depending on the presence or absence, respectively, of a ring of Hoechst 33342-positive chromatin surrounding the nucleolus. The aim of the present study was to test the developmental competence to blastocyst of the two types of oocytes. Here we show that following isolation, classification and culture of cumulus-free antral oocytes, 14.7% and 74.5% of NSN and SN oocytes, respectively, reached the metaphase II stage. When fertilised and further cultured none of the metaphase II NSN oocytes developed beyond the 2-cell stage whilst 47.4% of the metaphase II SN oocytes reached the 4-cell stage and 18.4% developed to blastocyst. The findings reported in this paper may contribute to improved procedures of female gamete selection for in vitro fertilisation of humans and farm animals. Furthermore, the selection of oocytes with better developmental potential may be of interest for studies on nuclear/cytoplasm interaction, particularly in nuclear-transfer experiments.

Human Achilles Tendon: Morphological and Morphometric Variations as a Function of Age

Aging of human Achilles tendon results in changes in both cellular and fibrous components. Cells flatten and become less numerous. Their thin and long cytoplasmatic projections tend to shorten and diminish in number. Tendon fibers lose their typical undulating appearance and become quite straight. Collagen fibril diameter, small and uniform in the neonatal period, becomes large and extremely variable from adolescence onwards. Age related morphometric changes include a decrease in the average, maximum diameter and density of collagen fibrils and an increase of fibril concentration. In our opinion these morphological and morphometric variations are strictly related to functional requirements.

Parcellation of human mesial area 6: cytoarchitectonic evidence for three separate areas.

The mesial sector of primate area 6 is usually described as consisting of two distinct areas: the supplementary motor area (SMA or SMA proper) and the pre‐SMA. Recent human brain imaging studies showed, however, that this subdivision is not completely satisfactory and that, most likely, SMA proper consists of two functionally distinct parts. In order to elucidate whether this hypothesis has an anatomical counterpart, we examined the cytoarchitectonic organization of human mesial area 6 in three brains of subjects deceased without any previous sign of neurological disorders. The data showed that human mesial area 6 consists of three separate cytoarchitectonic areas. Two of them are located mostly caudal to the vertical line transversing the anterior commissure (VCA line), the third one is located rostral to it. Given the location and some architectonic similarities between the two caudal areas, we named them caudal SMA (SMAc) and rostral SMA (SMAr). The area rostral to the VCA line is referred to as pre‐SMA. The possible functional role of the three areas is discussed.

Anti-inflammatory and cicatrizing activity of Echinacea pallida Nutt. root extract

Among the different species belonging to the Echinacea family, largely used in traditional medicine, Echinacea pallida, Echinacea purpurea and Echinacea angustifolia were investigated. These different species, due to their difficult identification, were commonly confused in the past and probably used indifferently for the same therapeutic purposes. In fact, the three species have in common, some pharmacological activities, based on the presence of active compounds that act additively and synergistically. Nevertheless, the composition of each species has slight variation in the amount of each active component. In particular, echinacoside, a caffeoyl derivative, is present in E. pallida and only in traces in E. angustifolia. It seems to have protective effects on skin connective tissue and to enhance wound healing. The anti-inflammatory and wound healing activities of echinacoside, compared with the ones of the total root extract of E. pallida and E. angustifolia, were examined in rats, after topical application. The tissues of the treated animals were evaluated after 24, 48 and 72 h treatment and excised for histological observation at the end of the experiment. Results confirm the good anti-inflammatory and wound healing properties of E. pallida and of its constituent echinacoside, with respect to E. purpurea and control. This activity probably resides in the antihyaluronidase activity of echinacoside.

Characterization of a novel peripheral pro-lipolytic mechanism in mice: role of VGF-derived peptide TLQP-21.

The peptides encoded by the VGF gene are gaining biomedical interest and are increasingly being scrutinized as biomarkers for human disease. An endocrine/neuromodulatory role for VGF peptides has been suggested but never demonstrated. Furthermore, no study has demonstrated so far the existence of a receptor-mediated mechanism for any VGF peptide. In the present study, we provide a comprehensive in vitro, ex vivo and in vivo identification of a novel pro-lipolytic pathway mediated by the TLQP-21 peptide. We show for the first time that VGF-immunoreactivity is present within sympathetic fibres in the WAT (white adipose tissue) but not in the adipocytes. Furthermore, we identified a saturable receptor-binding activity for the TLQP-21 peptide. The maximum binding capacity for TLQP-21 was higher in the WAT as compared with other tissues, and selectively up-regulated in the adipose tissue of obese mice. TLQP-21 increases lipolysis in murine adipocytes via a mechanism encompassing the activation of noradrenaline/β-adrenergic receptors pathways and dose-dependently decreases adipocytes diameters in two models of obesity. In conclusion, we demonstrated a novel and previously uncharacterized peripheral lipolytic pathway encompassing the VGF peptide TLQP-21. Targeting the sympathetic nerve-adipocytes interaction might prove to be a novel approach for the treatment of obesity-associated metabolic complications.

In-vitro permeation of bevacizumab through human sclera: effect of iontophoresis application

Objectives  Bevacizumab (Avastin) is a recombinant humanized monoclonal antibody used in ophthalmology (off‐label) for the treatment of neovascularization in diseases such as diabetic retinopathy and age‐related macular degeneration (wet form). Bevacizumab is currently administrated by repeated intravitreal injection, which can cause severe complications; a non‐invasive delivery route is therefore desirable. The passive permeation of bevacizumab through isolated human sclera was evaluated and the iontophoretic technique was explored as a method to enhance its transscleral transport in vitro.

Characterization of Rabbit Ear Skin as a Skin Model for in vitro Transdermal Permeation Experiments: Histology, Lipid Composition and Permeability

Aim: The aim of this work was to characterize rabbit ear skin in view of its use in transdermal permeation experiments. Method: The characterization included histological analysis of the tissue, qualitative and quantitative analysis of stratum corneum (SC) lipids, differential scanning calorimetry and permeation experiments (caffeine, nicotinamide, progesterone). As a reference, pig ear skin was used. Results: The results obtained show that rabbit ear skin has a similar SC thickness compared to pig skin although the viable epidermis has a different structure. The lipid composition of rabbit SC was similar to pig SC but was characterized by a lower content of ceramides and a higher content of cholesterol esters and triglycerides. In terms of permeability, rabbit ear skin was 4–7 times less permeable to hydrophilic compounds, probably because of the higher lipophilicity of its SC. The permeability to progesterone was comparable between isolated pig epidermis and rabbit ear skin. Conclusion: Overall, the results obtained in this work support the usefulness of rabbit ear skin as barrier for skin penetration studies, for both lipophilic and hydrophilic permeants.