In health and illness: does taste remain consistent? Exploring the influence of inflammation on taste perception through a systematic review and meta-analysis.

OBJECTIVE: Dysgeusia is characterized by a loss of taste perception, leading to malnutrition. This situation affects inflammatory conditions such as respiratory and neurological conditions, obesity, cancer, chemotherapy, aging, and many others. To date, there is not much information on the prevalence and risk of dysgeusia in an inflammatory condition; also, it is unclear which flavor is altered. MATERIALS AND METHODS: We systematically searched three databases from January 2018 to January 2023. Participants were children, adults, or elderly persons with an inflammatory condition and evaluated taste loss. A random effects model was used for statistical analysis to calculate the pooled odds ratio with its corresponding 95.0% confidence interval to estimate the probability of taste alteration (dysgeusia) in an inflammatory condition. RESULTS: The data allowed us to conduct a systematic review, including 63 original articles and 15 studies to perform the meta-analysis. The meta-analysis indicated a heterogenicity of 84.7% with an odds ratio of 3.25 (2.66-3.96), indicating a significant risk of Alzheimer's disease, SARS-CoV-2, chemotherapy, and rhinosinusitis. CONCLUSIONS: Inflammatory conditions and taste alterations are linked. Dysgeusia is associated with a higher risk of malnutrition and poorer general health status, especially in vulnerable populations.

Nanolithium, a New Treatment Approach to Alzheimer's Disease: A Review of Existing Evidence and Clinical Perspectives.

Lithium has been approved and used for several decades in the treatment of psychiatric disorders, and its potential effect in neurodegenerative diseases has been subject to increasing research interest in recent years. Nanolithium is a new experimental product using a novel drug-delivery technology (Aonys®), which optimizes its bioavailability while reducing its toxicity profile. Therapeutic doses of lithium used in Nanolithium are more than 50 times lower than the minimal dose of classical lithium salts. In this review we report data from non-clinical pharmacology studies supporting Nanolithium efficacy and the mechanism of action in Alzheimer's disease. GSK-3ß inhibition is thought to be central to Nanolithium's mechanism of action, triggering a reduction of the production of toxic amyloid plaques and decrease in tau hyperphosphorylation, which could potentially benefit both neuropsychiatric symptoms and cognitive decline. We then summarize outcomes from non-clinical proof-of-concept studies. These data supported the initiation of a currently ongoing phase II proof-of-concept study to evaluate the safety and efficacy of Nanolithium in patients with mild-to-severe Alzheimer's disease. We highlight key aspects of the study design. We finish this review with a discussion on the potential place of Nanolithium in the current and future Alzheimer's disease treatment landscape.

Using Digital Tools to Advance Alzheimer's Drug Trials During a Pandemic: The EU/US CTAD Task Force.

The 2020 COVID-19 pandemic has disrupted Alzheimer's disease (AD) clinical studies worldwide. Digital technologies may help minimize disruptions by enabling remote assessment of subtle cognitive and functional changes over the course of the disease. The EU/US Clinical Trials in Alzheimer's Disease (CTAD) Task Force met virtually in November 2020 to explore the opportunities and challenges associated with the use of digital technologies in AD clinical research. While recognizing the potential of digital tools to accelerate clinical trials, improve the engagement of diverse populations, capture clinically meaningful data, and lower costs, questions remain regarding the stability, validity, generalizability, and reproducibility of digital data. Substantial concerns also exist regarding regulatory acceptance and privacy. Nonetheless, the Task Force supported further exploration of digital technologies through collaboration and data sharing, noting the need for standardization of digital readouts. They also concluded that while it may be premature to employ remote assessments for trials of novel experimental medications, remote studies of non-invasive, multi-domain approaches may be feasible at this time.

Chronic Inhibition of FAAH Reduces Depressive-Like Behavior and Improves Dentate Gyrus Proliferation after Chronic Unpredictable Stress Exposure.

Symptoms of depressive disorders such as anhedonia and despair can be a product of an aberrant adaptation to stress conditions. Chronic unpredictable stress model (CUS) can generate an increase in the activity of the hypothalamic-pituitary-adrenal axis (HPA) and induce a reduction of neurotrophin signaling and the proliferation of neural progenitors in the adult dentate gyrus, together with increased oxidative stress. Levels of the endocannabinoid anandamide (AEA) seem to affect these depression-by-stress-related features and could be modulated by fatty acid amide hydrolase (FAAH). We aimed to evaluate the effects of FAAH inhibitor, URB597, on depressive-like behavior and neural proliferation of mice subjected to a model of CUS. URB597 was administered intraperitoneally at a dose of 0.2 mg/kg for 14 days after CUS. Depressive-like behaviors, anhedonia, and despair were evaluated in the splash and forced swimming tests, respectively. Alterations at the HPA axis level were analyzed using the relative weight of adrenal glands and serum corticosterone levels. Oxidative stress and brain-derived neurotrophic factor (BDNF) were also evaluated. Fluorescence immunohistochemistry tests were performed for the immunoreactivity of BrdU and Sox2 colabeling for comparison of neural precursors. The administration of URB597 was able to reverse the depressive-like behavior generated in mice after the model. Likewise, other physiological responses associated with CUS were reduced in the treated group, among them, increase in the relative weight of the adrenal glands, increased oxidative stress, and decreased BDNF and number of neural precursors. Most of these auspicious responses to enzyme inhibitor administration were blocked by employing a cannabinoid receptor antagonist. In conclusion, the chronic inhibition of FAAH generated an antidepressant effect, promoting neural progenitor proliferation and BDNF expression, while reducing adrenal gland weight and oxidative stress in mice under the CUS model.

Framework Implementation of the INSPIRE ICOPE-CARE Program in Collaboration with the World Health Organization (WHO) in the Occitania Region.

INTRODUCTION: Limiting the number of dependent older people in coming years will be a major economic and human challenge. In response, the World Health Organization (WHO) has developed the «Integrated Care for Older People (ICOPE)¼ approach. The aim of the ICOPE program is to enable as many people as possible to age in good health. To reach this objective, the WHO proposes to follow the trajectory of an individual's intrinsic capacity, which is the composite of all their physical and mental capacities and comprised of multiple domains including mobility, cognition, vitality / nutrition, psychological state, vision, hearing. OBJECTIVE: The main objective of the INSPIRE ICOPE-CARE program is to implement, in clinical practice at a large scale, the WHO ICOPE program in the Occitania region, in France, to promote healthy aging and maintain the autonomy of seniors using digital medicine. METHOD: The target population is independent seniors aged 60 years and over. To follow this population, the 6 domains of intrinsic capacity are systematically monitored with pre-established tools proposed by WHO especially STEP 1 which has been adapted in digital form to make remote and large-scale monitoring possible. Two tools were developed: the ICOPE MONITOR, an application, and the BOTFRAIL, a conversational robot. Both are connected to the Gerontopole frailty database. STEP 1 is performed every 4-6 months by professionals or seniors themselves. If a deterioration in one or more domains of intrinsic capacity is identified, an alert is generated by an algorithm which allows health professionals to quickly intervene. The operational implementation of the INSPIRE ICOPE-CARE program in Occitania is done by the network of Territorial Teams of Aging and Prevention of Dependency (ETVPD) which have more than 2,200 members composed of professionals in the medical, medico-social and social sectors. Targeted actions have started to deploy the use of STEP 1 by healthcare professionals (physicians, nurses, pharmacists,…) or different institutions like French National old age insurance fund (CNAV), complementary pension funds (CEDIP), Departmental Council of Haute Garonne, etc. Perspective: The INSPIRE ICOPE-CARE program draws significantly on numeric tools, e-health and digital medicine to facilitate communication and coordination between professionals and seniors. It seeks to screen and monitor 200,000 older people in Occitania region within 3 to 5 years and promote preventive actions. The French Presidential Plan Grand Age aims to largely implement the WHO ICOPE program in France following the experience of the INSPIRE ICOPE-CARE program in Occitania.

ß-Caryophyllene exerts protective antioxidant effects through the activation of NQO1 in the MPTP model of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder, caused by the selective death of dopaminergic neurons in the substantia nigra pars compacta. ß-caryophyllene (BCP) is a phytocannabinoid with several pharmacological properties, producing anti-inflammatory and antihypertensive effects. In addition, BCP protects dopaminergic neurons from neuronal death induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), yet it remains unclear if this effect is due to its antioxidant activity. To assess whether this is the case, the effect of BCP on the expression and activity of NAD(P)H quinone oxidoreductase (NQO1) was evaluated in mice after the administration of MPTP. Male C57BL/6 J mice were divided into four groups, the first of which received saline solution i.p. in equivalent volume and served as a control group. The second group received MPTP. The second group received MPTP hydrochloride (5 mg/kg, i.p.) daily for seven consecutive days. The third group received BCP (10 mg/kg) for seven days, administered orally and finally, the fourth group received MPTP as described above and BCP for 7 days from the fourth day of MPTP administration. The results showed that BCP inhibits oxidative stress-induced cell death of dopaminergic neurons exposed to MPTP at the same time as it enhances the expression and enzymatic activity of NQO1. Also, the BCP treatment ameliorated motor dysfunction and protected the dopaminergic cells of the SNpc from damage induced by MPTP. Hence, BCP appears to achieve at least some of its antioxidant effects by augmenting NQO1 activity, which protects cells from MPTP toxicity. Accordingly, this phytocannabinoid may represent a promising pharmacological option to safeguard dopaminergic neurons and prevent the progression of PD.

Oxidative, Reductive, and Nitrosative Stress Effects on Epigenetics and on Posttranslational Modification of Enzymes in Cardiometabolic Diseases.

Oxidative (OS), reductive (RS), and nitrosative (NSS) stresses produce carbonylation, glycation, glutathionylation, sulfhydration, nitration, and nitrosylation reactions. OS, RS, and NSS are interrelated since RS results from an overactivation of antioxidant systems and NSS is the result of the overactivation of the oxidation of nitric oxide (NO). Here, we discuss the general characteristics of the three types of stress and the way by which the reactions they induce (a) damage the DNA structure causing strand breaks or inducing the formation of 8-oxo-d guanosine; (b) modify histones; (c) modify the activities of the enzymes that determine the establishment of epigenetic cues such as DNA methyl transferases, histone methyl transferases, acetyltransferases, and deacetylases; (d) alter DNA reparation enzymes by posttranslational mechanisms; and (e) regulate the activities of intracellular enzymes participating in metabolic reactions and in signaling pathways through posttranslational modifications. Furthermore, the three types of stress may establish new epigenetic marks through these reactions. The development of cardiometabolic disorders in adult life may be programed since early stages of development by epigenetic cues which may be established or modified by OS, RS, and NSS. Therefore, the three types of stress participate importantly in mediating the impact of the early life environment on later health and heritability. Here, we discuss their impact on cardiometabolic diseases. The epigenetic modifications induced by these stresses depend on union and release of chemical residues on a DNA sequence and/or on amino acid residues in proteins, and therefore, they are reversible and potentially treatable.

Chitosan/copper nanocomposites: Correlation between electrical and antibacterial properties.

Correlation between electrical and antibacterial properties of chitosan/copper nanocomposites (CS/CuNPs) is investigated. We aim at achieving the minimum CuNPs concentration in a CS-matrix while keeping high antibacterial activity. UV-vis, TEM and XRD measurements confirms the formation of polygonal metallic CuNPs (ca. 30-50 nm). Interactions between NH2/OH groups of CS and CuNPs were determined by FTIR and XPS suggesting Cu chelation-induced mechanism during the CuNPs formation. DC electrical conductivity measurements reveals a percolation threshold at CuNPs volumetric concentration of ca. 0.143%. Antibacterial assays against Gram-positive bacteria and DC measurements helps correlate the antibacterial potency to the electron transfer between the negatively charged bacteria and CuNPs. Our study suggests that nanocomposite's maximum antibacterial activity is obtained below the electrical percolation threshold at extremely low CuNPs concentrations; this fact may prove useful in the design of nontoxic nanocomposites for biomedical applications.

Effect of inhibition of fatty acid amide hydrolase on MPTP-induced dopaminergic neuronal damage. / Efecto del inhibidor de amida hidrolasa de ácidos grasos en el daño neuronal dopaminérgico inducido por MPTP.

INTRODUCTION: Parkinson's disease (PD) is a neurodegenerative disorder characterised by balance problems, muscle rigidity, and slow movement due to low dopamine levels and loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The endocannabinoid system is known to modulate the nigrostriatal pathway through endogenous ligands such as anandamide (AEA), which is hydrolysed by fatty acid amide hydrolase (FAAH). The purpose of this study was to increase AEA levels using FAAH inhibitor URB597 to evaluate the modulatory effect of AEA on dopaminergic neuronal death induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). METHODS: Our study included 4 experimental groups (n = 6 mice per group): a control group receiving no treatment, a group receiving URB597 (0.2mg/kg) every 3 days for 30 days, a group treated with MPTP (30mg/kg) for 5 days, and a group receiving URB597 and subsequently MPTP injections. Three days after the last dose, we conducted a series of behavioural tests (beam test, pole test, and stride length test) to compare motor coordination between groups. We subsequently analysed immunoreactivity of dopaminergic cells and microglia in the SNpc and striatum. RESULTS: Mice treated with URB597 plus MPTP were found to perform better on behavioural tests than mice receiving MPTP only. According to the immunohistochemistry study, mice receiving MPTP showed fewer dopaminergic cells and fibres in the SNpc and striatum. Animals treated with URB597 plus MPTP displayed increased tyrosine hydroxylase immunoreactivity compared to those treated with MPTP only. Regarding microglial immunoreactivity, the group receiving MPTP showed higher Iba1 immunoreactivity in the striatum and SNpc than did the group treated with URB597 plus MPTP. CONCLUSION: Our results show that URB597 exerts a protective effect since it inhibits dopaminergic neuronal death, decreases microglial immunoreactivity, and improves MPTP-induced motor alterations.

Combined antibacterial/tissue regeneration response in thermal burns promoted by functional chitosan/silver nanocomposites.

We report the combined antibacterial/tissue regeneration responses to thermal burns promoted by functional chitosan/silver nanocomposites (CS/nAg) with ultralow silver content (0.018wt.%, 7-30nm). Our approach allows one to produce CS/nAg nanocomposites without silver nanoparticles (nAg) agglomeration, with bactericide potency higher than 1wt.% of nAg (ca. 10nm) content and, promoting the healing process in controlled thermal burns. CS/nAg films exhibit high antibacterial activity against S. aureus and P. aeruginosa after 1.5h of incubation, demonstrating the bacterial penetration into hydrated films and their interaction with nAg. Additionally, exceptional healing of induced thermal burns was obtained by increasing myofibroblasts, collagen remodeling, and blood vessel neoformation. These factors are associated with epiderma regeneration after 7days of treatment with no nAg release. Our results corroborate the controlled synthesis of nAg embedded in CS matrix with combined antibacterial/biocompatibility properties aiming to produce functional nanocomposites with potential use in wound dressing and health care applications.

Improving the mix of institutional and community care for older people with dementia: an application of the balance of care approach in eight European countries.

OBJECTIVES: To examine whether the mix of community and institutional long-term care (ILTC) for people with dementia (PwD) in Europe could be improved; assess the economic consequences of providing alternative services for particular groups of ILTC entrants and explore the transnational application of the 'Balance of Care' (BoC) approach. METHOD: A BoC study was undertaken in Estonia, Finland, France, Germany, the Netherlands, Spain, Sweden, and the UK as part of the RightTimePlaceCare project. Drawing on information about 2014 PwD on the margins of ILTC admission, this strategic planning framework identified people whose needs could be met in more than one setting, and compared the relative costs of the possible alternatives. RESULTS: The findings suggest a noteworthy minority of ILTC entrants could be more appropriately supported in the community if enhanced services were available. This would not necessarily require innovative services, but more standard care (including personal and day care), assuming quality was ensured. Potential cost savings were identified in all countries, but community care was not always cheaper than ILTC and the ability to release resources varied between nations. CONCLUSIONS: This is believed to be the first transnational application of the BoC approach, and demonstrates its potential to provide a consistent approach to planning across different health and social care systems. Better comparative information is needed on the number of ILTC entrants with dementia, unit costs and outcomes. Nevertheless, the findings offer important evidence on the appropriateness of current provision, and the opportunity to learn from different countries' experience.

Description of 1,108 older patients referred by their physician to the "Geriatric Frailty Clinic (G.F.C) for Assessment of Frailty and Prevention of Disability" at the gerontopole.

INTRODUCTION: Frailty is considered as an early stage of disability which, differently from disability, is still amenable for preventive interventions and is reversible. In 2011, the "Geriatric Frailty Clinic (G.F.C) for Assessment of Frailty and Prevention of Disability" was created in Toulouse, France, in association with the University Department of General Medicine and the Midi-Pyrénées Regional Health Authority. This structure aims to support the comprehensive and multidisciplinary assessment of frail older persons, to identify the specific causes of frailty and to design a personalized preventive plan of intervention against disability. In the present paper, we describe the G.F.C structure, organization, details of the global evaluation and preventive interventions against disability, and provide the main characteristics of the first 1,108 patients evaluated during the first two years of operation. METHODS: Persons aged 65 years and older, considered as frail by their physician (general practitioner, geriatrician or specialist) in the Toulouse area, are invited to undergo a multidisciplinary evaluation at the G.F.C. Here, the individual is assessed in order to detect the potential causes for frailty and/or disability. At the end of the comprehensive evaluation, the team members propose to the patient (in agreement with the general practitioner) a Personalized Prevention Plan (PPP) specifically tailored to his/her needs and resources. The G.F.C also provides the patient's follow-up in close connection with family physicians. RESULTS: Mean age of our population was 82.9 ± 6.1 years. Most patients were women (n=686, 61.9%). According to the Fried criteria, 423 patients (39.1%) were pre-frail, and 590 (54.5%) frail. Mean ADL (Activities of Daily Living) score was 5.5 ± 1.0. Consistently, IADL (Instrumental ADL) showed a mean score of 5.6 ± 2.4. The mean gait speed was 0.78 ± 0.27 and 25.6% (272) of patients had a SPPB (Short Physical Performance Battery) score equal to or higher than 10. Dementia was observed in 14.9% (111) of the G.F.C population according to the CDR scale (CDR ≥2). Eight percent (84) presented an objective state of protein-energy malnutrition with MNA (Mini Nutritional Assessment) score < 17 and 39.5% (414) were at risk of malnutrition (MNA=17-23.5). Concerning PPP, for 54.6% (603) of patients, we found at least one medical condition which needed a new intervention and for 32.8% (362) substantial therapeutic changes were recommended. A nutritional intervention was proposed for 61.8% (683) of patients, a physical activity intervention for 56.7% (624) and a social intervention for 25.7% (284). At the time of analysis, a one-year reassessment had been carried out for 139 (26.7%) of patients. CONCLUSIONS: The G.F.C was developed to move geriatric medicine to frailty, an earlier stage of disability still reversible. Its particularity is that it is intended for a single target population that really needs preventive measures: the frail elderly screened by physicians. The screening undergone by physicians was really effective because 93.6% of the subjects who referred to this structure were frail or pre-frail according to Fried's classification and needed different medical interventions. The creation of units like the G.F.C, specialized in evaluation, management and prevention of disability in frail population, could be an interesting option to support general practitioners, promote the quality of life of older people and increase life expectancy without disability.

Effects of bupropion on the ejaculatory response of male rats.

Chronic antidepressant treatment is associated with sexual side effects, particularly affecting the ejaculatory response. Bupropion (BP), an antidepressant inhibiting dopamine/noradrenaline reuptake, seems to have a low impact upon male sexual function. Ejaculation is regulated both at the brain and spinal cord by the spinal generator for ejaculation (SGE). We investigated the effects of chronic BP treatment on ejaculatory behavior and on SGE functioning. Sexually experienced male rats were intraperitoneally (i.p.) injected with BP (7.5 or 15 mg kg(-1)) during 14 days and tested for sexual behavior on days 1, 7 and 14 of treatment; these same males were used to evaluate the functioning of the SGE by recording the genital motor pattern for ejaculation (GMPE). Acute and chronic BP administration did not importantly modify copulatory behavior of male rats. Chronic treatment with the low dose of BP produced deficits in the functioning of the SGE that were restored by activation of the SGE through afferent stimulation. Conversely, chronic treatment with the high-dose of BP disrupted the functioning of the SGE, as the deficits were not compensated by activating the SGE through sensory stimulation. It is concluded that chronic BP at high doses alters the functioning of the SGE.

MAPT STUDY: A MULTIDOMAIN APPROACH FOR PREVENTING ALZHEIMER'S DISEASE: DESIGN AND BASELINE DATA.

OBJECTIVE: The Multidomain Alzheimer Preventive Trial (MAPT study) was designed to assess the efficacy of isolated supplementation with omega-3 fatty acid, an isolated multidomain intervention (consisting of nutritional counseling, physical exercise, cognitive stimulation) or a combination of the two interventions on the change of cognitive functions in frail subjects aged 70 years and older for a period of 3 years. Ancillary neuroimaging studies were additionally implemented to evaluate the impact of interventions on cerebral metabolism (FDG PET scans) and atrophy rate (MRIs), as well as brain amyloïd deposit (AV45 PET scans). DESIGN PATIENTS: 1680 subjects (mean age: 75.3 years; female: 64.8 %), enrolled by 13 memory clinics, were randomized into one of the following four groups: omega-3 supplementation alone, multidomain intervention alone, omega-3 plus multidomain intervention, or placebo. Participants underwent cognitive, functional and biological assessments at M6, M12, M24 and M36 visits. The primary endpoint is a change of memory function at 3 years, as assessed by the Free and Cued Selective Reminding test. All participants will be followed for 2 additional years after the 3-years intervention (MAPT PLUS extension study). INTERVENTIONS: 1/Omega-3 supplementation: two soft capsules daily as a single dose, containing a total of 400 mg docosahexaenoic acid (DHA), i.e., 800 mg docosahexaenoic acid per day, for 3 years. 2/ Multidomain intervention: collective training sessions conducted in small groups (6-8 participants) in twelve 120-minute sessions over the first 2 months (two sessions a week for the first month, and one session a week the second month) then a 60-minute session per month in the following three areas: nutrition, physical activity, and cognition until the end of the 3 years. In addition to the collective sessions, individualized preventive outpatient visits exploring possible risk factors for cognitive decline are performed at baseline, M12 and M24. BASELINE POPULATION: For cognition, the mean MMSE at baseline was 28.1 (± 1.6). About 58% and 42% of participants had a CDR score equal to 0 and 0.5, respectively. Regarding mobility status, 200 (11.9%) had a 4-m gait speed lower or equal to 0.8 m/s. According to the Fried criteria, 673 (42.1%) participants were considered pre frail, and 51 (3.2%) frail. The red blood cell DHA content was 26.1 ± 8.1 µg/g. Five hundred and three participants underwent baseline MRI. AV45 PET scans were performed in 271 individuals and preliminary results showed that 38.0% had a cortical SUVR > 1.17, which gave an indication of significant brain amyloïd deposit. DISCUSSION: The MAPT trial is presently the first largest and longest multidomain preventive trial relevant to cognitive decline in older adults with subjective memory complaints. The multidomain intervention designed for the MAPT trial is likely to be easily implemented within the general population.

Cognitive frailty: rational and definition from an (I.A.N.A./I.A.G.G.) international consensus group.

The frailty syndrome has recently attracted attention of the scientific community and public health organizations as precursor and contributor of age-related conditions (particularly disability) in older persons. In parallel, dementia and cognitive disorders also represent major healthcare and social priorities. Although physical frailty and cognitive impairment have shown to be related in epidemiological studies, their pathophysiological mechanisms have been usually studied separately. An International Consensus Group on "Cognitive Frailty" was organized by the International Academy on Nutrition and Aging (I.A.N.A) and the International Association of Gerontology and Geriatrics (I.A.G.G) on April 16th, 2013 in Toulouse (France). The present report describes the results of the Consensus Group and provides the first definition of a "Cognitive Frailty" condition in older adults. Specific aim of this approach was to facilitate the design of future personalized preventive interventions in older persons. Finally, the Group discussed the use of multidomain interventions focused on the physical, nutritional, cognitive and psychological domains for improving the well-being and quality of life in the elderly. The consensus panel proposed the identification of the so-called "cognitive frailty" as an heterogeneous clinical manifestation characterized by the simultaneous presence of both physical frailty and cognitive impairment. In particular, the key factors defining such a condition include: 1) presence of physical frailty and cognitive impairment (CDR=0.5); and 2) exclusion of concurrent AD dementia or other dementias. Under different circumstances, cognitive frailty may represent a precursor of neurodegenerative processes. A potential for reversibility may also characterize this entity. A psychological component of the condition is evident and concurs at increasing the vulnerability of the individual to stressors.

5-HT denervation of the adult rat prefrontal cortex induces changes in the expression of α4 and α7 nicotinic acetylcholine receptor subtypes.

INTRODUCTION: Nicotinic acetylcholine receptors (nAChRs) are widely expressed throughout several brain regions. Formation of the α4ß2 and α7 subtypes in particular is involved in the organisation of different types of memory. Furthermore, due to their location, these receptors can control the release of various types of neurotransmitters and contribute to synaptic plasticity. METHODS: Rats were divided into three groups, an experimental group (E), a sham-operated group, (S) and an intact group (T). In group E, stereotactic guidance was used to induce a chemical lesion with 1 µ/µL of 5,7-dihydroxytryptamine (5,7-DHT) in the anteroventral part of the dorsal raphe nucleus (DRN). In the sham-operated group (S), animals underwent surgery including delivery of the same excipient solution to the same site. The intact group (T) received no treatment whatsoever. Twenty days after surgery, animals in all groups were euthanised by decapitation to evaluate the expression of α4 and α7 nAChRs by means of molecular biology techniques. RESULTS: 5-HT denervation of the rat PFC differentially modified the expression of α4 and α7 receptors: while α4 receptor expression increased, α7 expression decreased. CONCLUSION: Expression differences observed between the two subtypes may be due to their separate locations. The α4 subtype is found in postsynaptic locations and may be related to adaptive changes in postsynaptic cells, while the location of α7 is presynaptic. This explains why the lesion and the elimination of 5-HT fibres in the CPF would cause a decrease in α7 expression.

[Expression of NMDA receptor subunits in rat prefrontal cortex with CCL4-induced hepatic damage after a treatment with Rosmarinus officinalis L]. / Expresión de las subunidades del receptor NMDA en la corteza prefrontal de la rata con daño hepático inducido con CCL4 después del tratamiento con Rosmarinus officinalis L.

INTRODUCTION: In cirrhosis some toxic substances accumulate in brain and modify the expression of several neuronal receptors. Thus, the use of medicinal plants such as Rosmarinus officinalis L. has been proposed in several pathologies due to its hepatoprotective, antioxidant and neuroprotective activity. In this study we evaluated the expression of the subunits NR1, NR2A and NR2B of the glutamate receptor in rat prefrontal cortex in a model of hepatic damage induced with carbon tetrachloride after a treatment with Rosmarinus officinalis L. METHODS: We used a total of 24 male Wistar rats weighing 80-90 g. body weight. We formed three study groups: control group (C) without a treatment, carbon tetrachloride group (CC14), and CC14 group plus Rosmarinus officinalis L (CCl4+ROM; 1.5 g/kg of extract orally). RESULTS: The expression of the NR1, NR2A and NR2B subunits in cirrhotic animals increased compared to the control group, however treatment with Rosmarinus officinalis L. was able to reduce this expression to normal levels compared with CC14 and CCl4+ROM groups. These results could be due to an improvement in hepatic function. CONCLUSION: Treatment with extract of Rosmarinus officinalis L. in cirrhotic animals modifies the expression of subunits of the NMDA receptor due to an improvement in hepatocellular function in the presence of antioxidant compounds and flavonoids.

[Structure and function of NMDA-type glutamate receptor subunits]. / Estructura y función de las subunidades del receptor a glutamato tipo NMDA.

INTRODUCTION: To review the physiology of the glutamate receptor subunits such as N-methyl-D-aspartate (NMDA). DEVELOPMENT: Glutamic acid (Glu) is the major excitatory neurotransmitter in the central nervous system which interacts with two types classified into two types: metabotropic and ionotropic. Ionotropic receptors are classified according to the affinity of their specific agonists: N-methyl-D-aspartate (NMDA), α-amino acid-3-hydroxy-5-methyl-4-isoxazole (AMPA) and kainic acid (KA). NMDA receptors are macromolecular structures that are formed by different combinations of subunits, NMDAR1 (NR1), NMDAR2 (NR2) and NMDAR3 (NR3) CONCLUSIONS: The study of this receptor has been of great interest due to its role in synaptic plasticity, but mainly due to the permeability it has to Ca(++) ion. This review examines the molecular composition of NMDA receptor and the variants of NR1 subunit edition in association with NR2 subunit dimer, the main form of this receptor. The composition, structure and function and their distinct expression patterns in both time and space, has shown the versatility and diversity of functionally different isoforms of the NR1 subunit and various pharmacological properties of the NR2 subunit.

HIF-1α expression in the hippocampus and peripheral macrophages after glutamate-induced excitotoxicity.

Hypoxia-inducible factor-1 alpha (HIF-1α) is a master transcription factor that regulates the response to hypoxia and ischemia and induces the expression of various genes, including vascular endothelial growth factor (VEGF) and erythropoietin (EPO). This study shows the systemic response of increased HIF-1α, EPO, and VEGF mRNA and protein. In addition, VEGF expression was increased in neurons and over-expressed in glial cells in a model of neuroexcitotoxicity in the hippocampus, in which rats were neonatally exposed to high glutamate concentrations. Simultaneous increases in HIF-1α, EPO and VEGF mRNA in peritoneal macrophages were also observed. Our study is consistent with the hypothesis that these genes exert a protective effect in response to neurotoxicity.