Julio Cesar Morales-Medina

A possible role of neuropeptide Y in depression and stress

Neuropeptide Y (NPY) mediates its physiological effects through at least four receptors known as Y(1), Y(2), Y(4), and Y(5). This peptide is one of the most abundant peptides in the central nervous system and is highly conserved throughout evolution. The most abundant receptors of the NPY family, the Y(1) and Y(2) receptors, are densely expressed in the cortex, hippocampus, and amygdala. These brain regions are particularly associated with mood disorders, stress responses, and memory processing. With this in mind, researchers suggested the involvement of NPY as well as the Y(1) and Y(2) receptors in affective disorders. Earlier studies showed that NPY and the Y(1) and Y(2) receptors mediate some aspects of depression-like disorders and stress responses in rodents. Recent research also suggests the involvement of the Y(4) and Y(5) receptors in emotion-related processes in rodents. In addition, human studies have consistently suggested a role for NPY in stress responses, whereas conflicting data have been obtained in relation to the role of NPY in depression-related illnesses. However, novel evidence from polymorphisms in the prepro-NPY gene has shed new light on the potential clinical relevance of NPY in depression. In this article, we review the literature from both animal and human studies regarding the contribution of NPY and its receptors in depression and stress.

Morphological reorganization after repeated corticosterone administration in the hippocampus, nucleus accumbens and amygdala in the rat.

Elevated levels of corticosteroids and stress play key roles in the pathophysiology of affective disorders. Corticosterone (CORT)-treated rats have emerged as a pharmacological model of depression-like behaviors. Previous studies have shown that CORT administration induces neuronal atrophy in the CA3 subfield of the hippocampus and laminae II/III of the prefrontal cortex. However, little attention has been given to other limbic structures such as the amygdala and the nucleus accumbens (NAcc). We investigated here whether 3 weeks of CORT administration in rats causes dendritic remodeling and spine density reorganization in the basolateral amygdala and pyramidal neurons of the CA1 subfield of the hippocampus as well as in spiny medium neurons of NAcc. Quantitative morphological analysis revealed retracted neuronal arborizations and modified configuration of length depending on branch order in medium spiny neurons of the NAcc of CORT-treated animals. Moreover, distal dendritic sections of the NAcc showed massive reductions in the number of spines caused by the CORT treatment. This treatment also induced a reduction in total dendritic length specific to fourth and sixth branch orders of pyramidal CA1 hippocampal neurons. These neurons also showed decreased branching and diminished number of spines. Finally, pyramidal neurons of the basolateral amygdala were apparently not significantly affected by the CORT treatment. Taken together, these data show for the first time neuronal morphological alterations in the NAcc in the CORT model of depression-like behaviors. Our results also add further information about the morphological reorganization occurring in CORT-sensitive regions of the limbic system.

Mechanisms and therapeutic effectiveness of lactobacilli

The gut microbiome is not a silent ecosystem but exerts several physiological and immunological functions. For many decades, lactobacilli have been used as an effective therapy for treatment of several pathological conditions displaying an overall positive safety profile. This review summarises the mechanisms and clinical evidence supporting therapeutic efficacy of lactobacilli. We searched Pubmed/Medline using the keyword ‘Lactobacillus’. Selected papers from 1950 to 2015 were chosen on the basis of their content. Relevant clinical and experimental articles using lactobacilli as therapeutic agents have been included. Applications of lactobacilli include kidney support for renal insufficiency, pancreas health, management of metabolic imbalance, and cancer treatment and prevention. In vitro and in vivo investigations have shown that prolonged lactobacilli administration induces qualitative and quantitative modifications in the human gastrointestinal microbial ecosystem with encouraging perspectives in counteracting pathology-associated physiological and immunological changes. Few studies have highlighted the risk of translocation with subsequent sepsis and bacteraemia following probiotic administration but there is still a lack of investigations on the dose effect of these compounds. Great care is thus required in the choice of the proper Lactobacillus species, their genetic stability and the translocation risk, mainly related to inflammatory disease-induced gut mucosa enhanced permeability. Finally, we need to determine the adequate amount of bacteria to be delivered in order to achieve the best clinical efficacy decreasing the risk of side effects.

A high calorie diet causes memory loss, metabolic syndrome and oxidative stress into hippocampus and temporal cortex of rats

A high calorie intake can induce the appearance of the metabolic syndrome (MS), which is a serious public health problem because it affects glucose levels and triglycerides in the blood. Recently, it has been suggested that MS can cause complications in the brain, since chronic hyperglycemia and insulin resistance are risk factors for triggering neuronal death by inducing a state of oxidative stress and inflammatory response that affect cognitive processes. This process, however, is not clear. In this study, we evaluated the effect of the consumption of a high‐calorie diet (HCD) on both neurodegeneration and spatial memory impairment in rats. Our results demonstrated that HCD (90 day consumption) induces an alteration of the main energy metabolism markers, indicating the development of MS in rats. Moreover, an impairment of spatial memory was observed. Subsequently, the brains of these animals showed activation of an inflammatory response (increase in reactive astrocytes and interleukin1‐β as well as tumor necrosis factor‐α) and oxidative stress (reactive oxygen species and lipid peroxidation), causing a reduction in the number of neurons in the temporal cortex and hippocampus. Altogether, these results suggest that a HCD promotes the development of MS and contributes to the development of a neurodegenerative process and cognitive failure. In this regard, it is important to understand the relationship between MS and neuronal damage in order to prevent the onset of neurodegenerative disorders. Synapse 69:421–433, 2015.

Neuronal and brain morphological changes in animal models of schizophrenia

Schizophrenia, a severe and debilitating disorder with a high social burden, affects 1% of the adult world population. Available therapies are unable to treat all the symptoms, and result in strong side effects. For this reason, numerous animal models have been generated to elucidate the pathophysiology of this disorder. All these models present neuronal remodeling and abnormalities in spine stability. It is well known that the complexity in dendritic arborization determines the number of receptive synaptic contacts. Also the loss of dendritic spines and arbor stability are strongly associated with schizophrenia. This review evaluates changes in spine density and dendritic arborization in animal models of schizophrenia. By understanding these changes, pharmacological treatments can be designed to target specific neural systems to attenuate neuronal remodeling and associated behavioral deficits.

Narrative review of telemedicine consultation in medical practice

Background The use of telemedicine has grown across several medical fields, due to the increasing number of “e-patients”. Objective This narrative review gives an overview of the growing use of telemedicine in different medical specialties, showing how its use can improve medical care. Methods A PubMed/Medline, Embase, Web of Science, and Scopus search was performed using the following keywords: telemedicine, teleconsultation, telehealth, e-health, and e-medicine. Selected papers from 1996 to 2014 were chosen on the basis of their content (quality and novelty). Results Telemedicine has already been applied to different areas of medical practice, and it is as effective as face-to-face medical care, at least for the diagnosis and treatment of some pathological conditions. Conclusion Telemedicine is time- and cost-effective for both patients and health care professionals, encouraging its use on a larger scale. Telemedicine provides specialist medical care to patients who have poor access to hospitals, and ensures continuity of care and optimal use of available health resources. The use of telemedicine opens new perspectives for patients seeking a medical second opinion for their pathology, since they can have remote access to medical resources that would otherwise require enormous costs and time.

Chronic administration of the Y2 receptor antagonist, JNJ-31020028, induced anti-depressant like-behaviors in olfactory bulbectomized rat.

Recent studies from our groups have shown that BIIE0246, a Y2 receptor antagonist, has antidepressant effect in olfactory bulbectomized (OBX) rat. However, its complex structure and high molecular weight limit its usefulness as an in vivo pharmacological tool. Alternatively, the novel and brain penetrant Y2 receptor antagonist, JNJ-31020028 is a useful tool to investigate the in vivo function of the Y2 receptor. In the present study, we evaluated the effect of chronic intracerebroventricular (icv) administration of JNJ-31020028 in a battery of behavioral tests in an animal model that mimics several deficits observed in the human depression, the OBX rat. Chronic administration of JNJ-31020028 induced a decrease in immobility time in the forced swim test in OBX while had no effect in control animals. Additionally, it decreased number of grooming events in OBX animals, but had no effects on some other behavioral deficits observed such as rearing and hyperlocomotion. Furthermore, JNJ-31020028 had no effect on behavior tests that are commonly used to evaluate anxiety, namely the social interaction test in both OBX and control animals. These data indicate that similar to BIIE0246, JNJ-31020028 also has antidepressant like effects in the OBX model.

Effectiveness and Safety of Arnica montana in Post-Surgical Setting, Pain and Inflammation.

Arnica montana has been widely used as a homeopathic remedy for the treatment of several inflammatory conditions in pain management and postoperative settings. This review gives an overview of the therapeutic use of Arnica montana in the above-mentioned fields also focusing on its mechanisms of action learned from animal models and in vitro studies. Arnica montana is more effective than placebo when used for the treatment of several conditions including post-traumatic and postoperative pain, edema, and ecchymosis. However, its dosages and preparations used have produced substantial differences in the clinical outcome. Cumulative evidence suggests that Arnica montana may represent a valid alternative to non-steroidal anti-inflammatory drugs, at least when treating some specific conditions.

Experimental and Clinical Efficacy of Two Hyaluronic Acid-based Compounds of Different Cross-Linkage and Composition in the Rejuvenation of the Skin

ABSTRACTBackgroundIn the field of aesthetic medicine there is an increasing demand for safe and effective hyaluronic acid (HA) fillers to counteract the aging process.Methods and AimsWe designed a study to evaluate the safety and histological biocompatibility of Aliaxin® Global Performance, a cross-linked HA filler and Viscoderm® Skinkò E, a product composed of non-cross-linked HA and a complex including vitamins, antioxidants, amino acids and minerals injected into the skin of guinea pigs. Then, we translated our findings into the clinical setting, administering a combination of these compounds to patients seeking a facial rejuvenation procedure targeting moderate-to-severe wrinkles affecting the nasolabial folds.ResultsThe animal study showed that the two compounds did not induce any significant inflammatory reactions and increased collagen and elastic fibers in the skin. In the clinical setting, injection of Aliaxin® Global Performance, followed by Viscoderm® Skinkò E, resulted in a higher improvement in nasolabial fold hydration, trans-epidermal water loss and wrinkle aesthetic appearance, if compared with a protocol based on Aliaxin® Global Performance alone.ConclusionIn summary, we show evidence on the safety and mechanism underlying two new HA-based compounds of different cross-linkage and composition, proposing that they can be safely used in combination in patients seeking facial rejuvenation procedures with long-lasting efficacy.

Neuropeptide Y and its Role in Anxiety-related Disorders

Neuropeptide Y (NPY) is one of the most abundant peptide in the brain and has been implicated in various biological functions. Pre-clinical and clinical investigations have suggested that NPY, acting on specific receptors, has direct role in several psychiatric disorders, including depression and anxiety-related illnesses, which will be reviewed in this chapter. Increasing support for a role for NPY in mood disorders has been obtained over the past few years. The Y1, Y2 and Y4 receptor subtypes have been particularly involved in these behaviours. For example, we reported that NPY Y2 knockout mice display anxiolytic-like phenotype as assessed in the elevated plus maze and open field tests, suggesting a role of this receptor subtype in anxiety-related behaviours. Moreover, NPY Y2 knockout mice display memory retention deficits as evaluated in the Morris water maze and object recognition tests, while acquisition performance, swim speed and visible platform performance were not significantly different between knockout and wild-type mice. Additionally, young and old rats overexpressing NPY were found to be resistant to acute physical restrain stress, but rather surprisingly, no memory deficit was observed in old transgenic rats, contrasting with data obtained in young transgenic animals. Aged NPY transgenic rats and NPY Y2 knockout mice exhibit anxiolytic-like phenotypes, in accordance with results observed in younger animals. Interestingly, the ontogeny of various NPY receptor subtypes suggest further that they may be implicated in the etiology of anxiety-like phenotype observed in maternally deprived animals as important changes in NPY receptor distribution and levels occur during this critical period, especially for the Y2 receptor subtype. Taken together, these results support the hypothesis that NPY and its receptors may be involved in the regulation of anxiety-related behaviours and provide evidence that this neuropeptide family is an attractive drug development target for these disorders.