Search

Given the increased prevalence of overweight and obesity in adults in Colombia, estimating the effect of sociodemographic factors on overweight and obesity is crucial for creating and implementing public health policies. A pooled analysis was performed using a multinomial logistic regression model through Colombian Nutritional Situation Surveys held in 2010 and 2015. The study included Colombian adults between 18 and 64 years old (n = 162,119). Overall, the prevalence of obesity increased from 16.47 percent in 2010 to 18.67 percent in 2015, being higher in women than in men in both surveys. Multinomial logistic regression analysis revealed that the most critical factor of being overweight and obese were older age, having a higher level of education, being engaged in household activities, and living in regions other than the country's capital. Additionally, for obesity, belonging to the Afro Colombian racial-ethnic group and being a woman were associated with an increased probability. In conclusion, these results provide more information on the sociodemographic factors related to overweight and obesity, which will help focus public health policies on higher-risk populations, such as racial-ethnic communities., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The brain and spinal cord originate from a neural tube that is preceded by a flat structure known as the neural plate during early embryogenesis. In humans, failure of the neural plate to convert into a tube by the fourth week of pregnancy leads to neural tube defects (NTDs), birth defects with serious neurological consequences. The signaling mechanisms governing the process of neural tube morphogenesis are unclear. Here we show that in Xenopus laevis embryos, neural plate cells release glutamate during neural plate folding in a Ca 2+ and vesicular glutamate transporter-1 (VGluT1)-dependent manner. Vesicular release of glutamate elicits Ca 2+ transients in neural plate cells that correlate with activation of Erk1/2. Knocking down or out VGluT1 leads to NTDs through increased expression of Sox2, neural stem cell transcription factor, and neural plate cell proliferation. Exposure during early pregnancy to neuroactive drugs that disrupt these signaling mechanisms might increase the risk of NTDs in offspring.

Leishmaniasis is a significant public health concern, with dogs as the primary reservoir in urban scenarios and facilitating transmission. Diagnosing infected dogs is a crucial step for public health interventions, and the development of new diagnostic platforms can significantly enhance efforts in various regions worldwide. Given the limited availability of diagnostic methods in Colombia, this study evaluates the effectiveness of an Indirect Enzyme-Linked Immunosorbent Assay (ELISA) based on the recombinant protein rLicNTPDase-2 to detect Leishmania in infected dogs. Serum samples were collected from dogs in both endemic and non-endemic areas and classified as natural standards based on prior parasitological diagnoses. The results revealed 24 true positives (TP) and 9 true negatives (TN). Subsequently, the test was then validated with samples from symptomatic and asymptomatic animals, alongside the standards, yielding a specificity of 96 %, a sensitivity of 81 %, efficiency of 90.6 %, a positive predictive value of 92.8 %, and a negative predictive value of 89.6 %. The positive likelihood ratio (RV+) was 20, while the negative likelihood ratio (RV-) was 0.19, indicating high relevance and a robust clinical utility. The area under the curve (AUC) was 1.00, suggesting that the test has excellent discriminatory ability, significantly deviating from the reference diagonal. This is further supported by the significant difference(p < 0.0001) between TN and TP results determined by Fisher's exact test. Involving 163 animals showed 47 % positive and 46 % negative results with a significant difference (p < 0.05) in the mean optical density (OD) values between positive and negative samples. These findings indicate that the ELISA test effectively differentiates between positive and negative samples based on OD values. This study suggests that ELISA based on the recombinant antigen rLicNTPDase-2 could serve as a viable alternative for the serodiagnosis of leishmaniasis in canines in Colombia., Competing Interests: Declaration of competing interest There are no competing interests that may influence the results of this study., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Obesity rates in Colombia are increasing, with variations among racial and ethnic groups. Studies on adult obesity often address socio-economic status, gender, and education but neglect racial-ethnic influences, notably in areas like Quibdó. Therefore, based on the theory of triadic influence, we conducted a qualitative study to identify biobehavioural, social, and cultural phenomena that, from the perspectives of the participants, influence the onset of obesity in Afro-Colombian and indigenous in Quibdó in 2022. The stratification variables were race, ethnicity (Afro-Colombian and Indigenous), and educational level (secondary or higher). Based on a literature review of qualitative studies that commonly explored food culture, nutritional status, and physical activity in analysing obesity within racial and ethnic populations, we incorporated these categories into our research methodology through semi-structured interviews. A framework analysis was used as a qualitative methodology to organise and analyse the collected data. We conducted 21 semi-structured interviews, 13 with the Afro-Colombian population and eight with indigenous inhabitants. The results indicate that cultural beliefs, forced displacement/migration, and alterations in public order have resulted in changes in food security, food culture, and physical activity practices, affecting the onset of obesity. Notably, distinctions in cultural beliefs regarding food culture and health as factors influencing obesity were observed between Afro-Colombians and the Indigenous populations; however, educational differences within the same racial ethnic group were not predominant. Findings indicate obesity is influenced by cultural, social, and biobehavioural factors, especially in regions with racial-ethnic communities facing complex conditions, necessitating targeted racial-ethnic public health policies., Competing Interests: The authors declare no competing interests., (© The Author(s) 2024.)

Background: Congenital heart disease is the most common congenital condition worldwide, with a prevalence of 80 cases per 10 000 live births. In addition to perinatal morbidity and mortality, it entails long-term consequences such as multiple surgeries, prolonged hospitalizations, lifelong cardiac follow-up, reduced quality of life, risk of heart failure, and premature mortality in adulthood. This significant health and economic burden on healthcare systems and families highlights the relevance of evaluating the cost-effectiveness of methods for early detection of this condition. Objective: To conduct a systematic literature review (SLR) to identify and analyze existing economic evaluations on prenatal detection of congenital heart diseases through ultrasound, focusing on the reported cost-effectiveness results and the methodological quality of the evaluated studies according to established criteria. Methods: An SLR of economic evaluations was conducted following PRISMA guidelines. A quantitative synthesis of key methodological components of each economic evaluation was performed. The incremental medical costs, effectiveness measures, and cost-effectiveness ratios reported in each study were compiled and compared. The methodological quality was assessed according to compliance with the 24 CHEERS criteria. Results: We found 785 articles, of which only 7 met all inclusion criteria. Most were cost-effectiveness analyses, with the most common outcome being number of cases detected. Screening with only 4-chamber views interpreted by general practitioners or cardiologists were dominant strategies compared with screening with 4-chamber plus outflow views interpreted by a general practitioner. Fetal echocardiography was most effective but most expensive. Screening with 4-chamber and outflow view, followed by referral to a specialist, were recommended as the least expensive strategy per defect detected. On average, articles met 17 of the 24 CHEERS criteria. Discussion: While recent cost-effectiveness analyses demonstrated improved methodological quality, there was a lack of homogeneity due to differences in comparators and population subgroups analyzed. Despite this heterogeneity, fetal ultrasonography screening was consistently identified as a cost-effective strategy, with its cost-effectiveness heavily influenced by the expertise of the interpreting physician. Conclusion: Most studies recommend implementing obstetric ultrasonography screening, without routine fetal echocardiography, for detecting congenital heart diseases.

Indole alkaloids are the main bioactive molecules of the Gelsemium genus plants. Diverse reports have shown the beneficial actions of Gelsemium alkaloids on the pathological states of the central nervous system (CNS). Nevertheless, Gelsemium alkaloids are toxic for mammals. To date, the molecular targets underlying the biological actions of Gelsemium alkaloids at the CNS remain poorly defined. Functional studies have determined that gelsemine is a modulator of glycine receptors (GlyRs) and GABA A receptors (GABA A Rs), which are ligand-gated ion channels of the CNS. The molecular and physicochemical determinants involved in the interactions between Gelsemium alkaloids and these channels are still undefined. We used electrophysiological recordings and bioinformatic approaches to determine the pharmacological profile and the molecular interactions between koumine, gelsemine, gelsevirine, and humantenmine and these ion channels. GlyRs composed of α1 subunits were inhibited by koumine and gelsevirine (IC 50 of 31.5 ± 1.7 and 40.6 ± 8.2 μM, respectively), while humantenmine did not display any detectable activity. The examination of GlyRs composed of α2 and α3 subunits showed similar results. Likewise, GABA A Rs were inhibited by koumine and were insensitive to humantenmine. Further assays with chimeric and mutated GlyRs showed that the extracellular domain and residues within the orthosteric site were critical for the alkaloid effects, while the pharmacophore modeling revealed the physicochemical features of the alkaloids for the functional modulation. Our study provides novel information about the molecular determinants and functional actions of four major Gelsemium indole alkaloids on inhibitory receptors, expanding our knowledge regarding the interaction of these types of compounds with protein targets of the CNS.

In Colombia, the prevalence of obesity has been increasing in recent years due to changes in dietary and nutritional patterns. While previous studies have focussed on describing obesity and its associated factors, they have mainly used a cross-sectional methodology. Accordingly, this study aims to conduct a descriptive quasi-cohort analysis to capture age-specific cohort trends in body mass index (BMI) according to sex and ethnicity (indigenous, Afro-Colombian, and the remaining population). The study utilised data from the National Survey of the Nutritional Situation in Colombia (ENSIN) conducted in 2005, 2010, and 2015 that included 214,136 individuals aged 20-64 years after screening. Data on ethnicity were only available from the 2010 and 2015 surveys. Overall, the prevalence of obesity increased by 6.1 percentage points (from 15.2% to 21.3%) between 2005 and 2015 (men from 10.4% to 15.7%; women from 18.2% to 25.7%). Among Afro-Colombians, obesity rose 6.6 percentage points (from 19.4% to 26.0%), again more so in women than in men (2015: 35.2% versus 17.8%). Among indigenous people, the proportion increased by 5.3 percentage points (from 13.5% to 18.8%), with women reporting highest rates (2015: 23.7% against 12.6% in men). Age- and cohort-specific results also indicate that recent adult cohorts are experiencing sharp increases in BMI, for example, while 25-29-year-old males born in 1975-1979 had a BMI of 24.2 kg/m 2 , among 40-44-year-olds of the same cohort, this equalled 26.8 kg/m 2 . In the case of women, these age differences in BMI among the same cohort are even greater (24.4 and 28.0 kg/m 2 ). In summary, the results of this study indicate that Colombia is still in the early stages of the obesity transition, urging the need to monitor obesity trends in Colombia from both an age and cohort perspective. To achieve this, longitudinal surveys or repeated cross-sectional surveys like the ENSIN could be utilised.

Chenopodium quinoa Willd. is a native species that originated in the High Andes plateau (Altiplano) and its cultivation spread out to the south of Chile. Because of the different edaphoclimatic characteristics of both regions, soils from Altiplano accumulated higher levels of nitrate ( NO 3 - ) than in the south of Chile, where soils favor ammonium (NH 4 + ) accumulation. To elucidate whether C. quinoa ecotypes differ in several physiological and biochemical parameters related to their capacity to assimilate NO 3 - and NH 4 + , juvenile plants of Socaire (from Altiplano) and Faro (from Lowland/South of Chile) were grown under different sources of N ( NO 3 - or NH 4 + ). Measurements of photosynthesis and foliar oxygen-isotope fractionation were carried out, together with biochemical analyses, as proxies for the analysis of plant performance or sensitivity to NH 4 + . Overall, while NH 4 + reduced the growth of Socaire, it induced higher biomass productivity and increased protein synthesis, oxygen consumption, and cytochrome oxidase activity in Faro. We discussed that ATP yield from respiration in Faro could promote protein production from assimilated NH 4 + to benefit its growth. The characterization of this differential sensitivity of both quinoa ecotypes for NH 4 + contributes to a better understanding of nutritional aspects driving plant primary productivity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jerez, Ortiz, Castro, Escobar, Sanhueza, Del-Saz, Ribas-Carbo, Coba de la Peña, Ostria-Gallardo, Fischer, Castro and Bascunan-Godoy.)

Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by cognitive impairment that increasingly affects the elderly. AD's main features have been related to cellular and molecular events, including the aberrant aggregation of the amyloid beta peptide (Aβ), Ca 2+ dyshomeostasis, and increased mitochondria-associated membranes (MAMs). Transglutaminase type 2 (TG2) is a ubiquitous enzyme whose primary role is the Ca 2+ -dependent proteins transamidation, including the Aβ peptide. TG2 activity has been closely related to cellular damage and death. We detected increased TG2 levels in neuronal cells treated with Aβ oligomers (AβOs) and hippocampal slices from J20 mice using cellular and molecular approaches. In this work, we characterized the capacity of TG2 to interact and promote Aβ toxic aggregates (AβTG2). AβTG2 induced an acute increase in intracellular Ca 2+ , miniature currents, and hiperexcitability, consistent with an increased mitochondrial Ca 2+ overload, IP3R-VDAC tethering, and mitochondria-endoplasmic reticulum contacts (MERCs). AβTG2 also decreased neuronal viability and excitatory postsynaptic currents, reinforcing the idea of synaptic failure associated with MAMs dysregulation mediated by TG2. Z-DON treatment, TG2 inhibitor, reduced calcium overload, mitochondrial membrane potential loss, and synaptic failure, indicating an involvement of TG2 in a toxic cycle which increases Aβ aggregation, Ca 2+ overload, and MAMs upregulation. These data provide novel information regarding the role TG2 plays in synaptic function and contribute additional evidence to support the further development of TG2 inhibitors as a disease-modifying strategy for AD., Competing Interests: Conflict of interest statement None., (Copyright © 2023. Published by Elsevier Masson SAS.)

Lysolecithin might increase ruminal and intestinal emulsification, leading to increased digestibility, but there is minimum information about which is the most appropriate phase to start supplementation and its impacts on feedlot performance and muscle fatty acid profile. Two experiments were conducted to evaluate the effects of phase-feeding of Lysoforte™ eXtend (LYSO). In the first experiment, 1,760 predominantly Bos indicus bullocks (initial body weight of 400 ± 0.561 kg) were allocated in a complete randomized block design. LYSO was supplemented at 1 g/1% of ether extract from the diet. Treatments were no LYSO supplementation (NON); LYSO starting during the growing period and continuing during the finishing period; LYSO starting during the finishing period (FIN); and LYSO during adaptation, growing, and finishing periods (ALL). In the second experiment, the same treatments were evaluated with 96 bullocks (64 Nellore and 32½ Nellore × ½ Angus) in a 4 × 2 factorial arrangement (treatments × genotype). For both studies, intake and average daily gain were accessed; carcass characteristics were evaluated in the first experiment, while digestibility of nutrients and profile of muscle fatty acids were measured in the second experiment. In the first experiment, LYSO increased final body weight ( P < 0.022) and average daily gain (GRO and FIN; P < 0.05). In the second study, a treatment × breed × feeding phase interaction was observed with Nellore having a greater average daily gain ( P < 0.05) than crossbreds in every feeding phase that LYSO was introduced to the diet. A treatment × feeding phase interaction was observed for digestibility, such that LYSO increased total dry matter ( P = 0.004), crude protein ( P = 0.043), and NDF ( P = 0.001) digestibility during the finishing period. A treatment × breed × day classification was observed ( P < 0.05). During the finishing phase, crossbreds treated with LYSO had greater DMI ( P < 0.05) on very hot days than NON. Also, animals treated with LYSO presented a greater C18:3 n3 concentration ( P = 0.047) in the longissimus . Overall, feeding LYSO during GRO and FIN enhanced feedlot performance and should lead to higher intakes during very hot days of the finishing feeding period., Competing Interests: MC and LG were employed by Kemin Industries. JC and RC were consultants to Nutribeef, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pacheco, Oliveira Gusmão, Moura, Capelari, Greco, Carvalho, Cervieri, Castro, de Alencar Beserra, Campanelli, Cabral, Carvalho, Lanna, Neto, Galyean and Maia.)

"Memory imprint" refers to the process when prior exposure to stress prepares the plant for subsequent stress episodes. Seed priming is a strategy to change the performance of seedlings to cope with stress; however, mechanisms associated with the metabolic response are fragmentary. Salinity is one of the major abiotic stresses that affect crop production in arid and semiarid areas. Chenopodium quinoa Willd. (Amaranthaceae) is a promising crop to sustain food security and possesses a wide genetic diversity of salinity tolerance. To elucidate if the metabolic memory induced by seed halo-priming (HP) differs among contrasting saline tolerance plants, seeds of two ecotypes of Quinoa (Socaire from Atacama Salar, and BO78 from Chilean Coastal/lowlands) were treated with a saline solution and then germinated and grown under different saline conditions. The seed HP showed a more positive impact on the sensitive ecotype during germination and promoted changes in the metabolomic profile in both ecotypes, including a reduction in carbohydrates (starch) and organic acids (citric and succinic acid), and an increase in antioxidants (ascorbic acid and α-tocopherol) and related metabolites. These changes were linked to a further reduced level of oxidative markers (methionine sulfoxide and malondialdehyde), allowing improvements in the energy use in photosystem II under saline conditions in the salt-sensitive ecotype. In view of these results, we conclude that seed HP prompts a "metabolic imprint" related to ROS scavenger at the thylakoid level, improving further the physiological performance of the most sensitive ecotype., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cifuentes, González, Pinto-Irish, Álvarez, Coba de la Peña, Ostria-Gallardo, Franck, Fischer, Barros, Castro, Ortiz, Sanhueza, Del-Saz, Bascunan-Godoy and Castro.)

Neurulation is a crucial process in the formation of the central nervous system (CNS), which begins with the folding and fusion of the neural plate, leading to the generation of the neural tube and subsequent development of the brain and spinal cord. Environmental and genetic factors that interfere with the neurulation process promote neural tube defects (NTDs). Connexins (Cxs) are transmembrane proteins that form gap junctions (GJs) and hemichannels (HCs) in vertebrates, allowing cell-cell (GJ) or paracrine (HCs) communication through the release of ATP, glutamate, and NAD + ; regulating processes such as cell migration and synaptic transmission. Changes in the state of phosphorylation and/or the intracellular redox potential activate the opening of HCs in different cell types. Cxs such as Cx43 and Cx32 have been associated with proliferation and migration at different stages of CNS development. Here, using molecular and cellular biology techniques (permeability), we demonstrate the expression and functionality of HCs-Cxs, including Cx46 and Cx32, which are associated with the release of ATP during the neurulation process in Xenopus laevis . Furthermore, applications of FGF2 and/or changes in intracellular redox potentials (DTT), well known HCs-Cxs modulators, transiently regulated the ATP release in our model. Importantly, the blockade of HCs-Cxs by carbenoxolone (CBX) and enoxolone (ENX) reduced ATP release with a concomitant formation of NTDs. We propose two possible and highly conserved binding sites (N and E) in Cx46 that may mediate the pharmacological effect of CBX and ENX on the formation of NTDs. In summary, our results highlight the importance of ATP release mediated by HCs-Cxs during neurulation.

The Gelsemium elegans plant preparations have shown beneficial activity against common diseases, including chronic pain and anxiety. Nevertheless, their clinical uses are limited by their toxicity. Gelsemine, one of the most abundant alkaloids in the Gelsemium plants, have replicated these therapeutic and toxic actions in experimental behavioral models. However, the molecular targets underlying these biological effects remain unclear. The behavioral activity profile of gelsemine suggests the involvement of GABA A receptors (GABA A Rs), which are the main biological targets of benzodiazepines (BDZs), a group of drugs with anxiolytic, hypnotic, and analgesic properties. Here, we aim to define the modulation of GABA A Rs by gelsemine, with a special focus on the subtypes involved in the BDZ actions. The gelsemine actions were determined by electrophysiological recordings of recombinant GABA A Rs expressed in HEK293 cells, and of native receptors in cortical neurons. Gelsemine inhibited the agonist-evoked currents of recombinant and native receptors. The functional inhibition was not associated with the BDZ binding site. We determined in addition that gelsemine diminished the frequency of GABAergic synaptic events, likely through a presynaptic modulation. Our findings establish gelsemine as a negative modulator of GABA A Rs and of GABAergic synaptic function. These pharmacological features discard direct anxiolytic or analgesic actions of gelsemine through GABA A Rs but support a role of GABA A Rs on the alkaloid induced toxicity. On the other hand, the presynaptic effects of the alkaloid provide an additional mechanism to explain their beneficial effects. Collectively, our results contribute novel information to improve understanding of gelsemine actions in the mammalian nervous system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Marileo, Gavilán, San Martín, Lara, Sazo, Muñoz-Montesino, Castro, Burgos, Leiva-Salcedo, Aguayo, Moraga-Cid, Fuentealba and Yévenes.)

The main strategy for the treatment of epilepsy is the use of pharmacological agents known as antiseizure medication (ASM). These drugs control the seizure onset and improves the life expectancy and quality of life of patients. Several ASMs are contraindicated during pregnancy, due to a potential teratogen risk. For this reason, the pharmacological treatments of the pregnant Women with Epilepsy (WWE) need comprehensive analyses to reduce fetal risk during the first trimester of pregnancy. The mechanisms by which ASM are teratogens are still under study and scientists in the field, propose different hypotheses. One of them, which will be addressed in this review, corresponds to the potential alteration of ASM on ion channels and proteins involved in relevant signaling and cellular responses (i.e., migration, differentiation) during embryonic development. The actual information related to the action of ASM and its possible targets it is poorly understood. In this review, we will focus on describing the eventual presence of some ion channels and synaptic proteins of the neurotransmitter signaling pathways present during early neural development, which could potentially interacting as targets of ASM. This information leads to elucidate whether these drugs would have the ability to affect critical signaling during periods of neural development that in turn could explain the fetal malformations observed by the use of ASM during pregnancy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Castro, Pinto-Borguero, Yévenes, Moraga-Cid and Fuentealba.)

Introduction: Bone defects hinder implant positioning. Vertical bone deficiency is the most challenging for clinical treatment, due to the high sensitivity of the technique and frequent intra- and postoperative complications. An alternative treatment for vertical defects is guided bone regeneration with simultaneous implantation; however, few studies have evaluated its effectiveness over time., Objective: To evaluate peri-implant tissue stability in a dental implant simultaneously positioned in an aesthetic zone of an area of zone vertical bone regeneration 3 years after functional load., Case Presentation: A 62-year-old male presented with the absence of the right lateral incisor and vertical bone defect of 3mm. His initial condition affected the relation of zenith points, causing disharmony. After case evaluation, vertical guided bone regeneration and simultaneous dental implants were performed to obtain a vertical bone gain of 3mm. The implant was rehabilitated with a zirconium crown and evaluated 3 years after functional loading., Conclusion: Vertical guided bone regeneration and simultaneous dental implant in the aesthetic zone in small bone defects (<4 mm) is an appropriate surgical and prosthetic technique to reduce surgical time, providing stability of peri-implant tissues even 3 years after functional implant loading., Competing Interests: Conflict of interests: The authors do not report any conflict of interest

In the midst of the health emergency caused by COVID-19 in Colombia, strategies have been generated to strengthen food security and sovereignty. Among the mechanisms adopted by urban and rural communities and local governments are alternative ways of obtaining food, one of which is trueque, which allows the exchange of food produced by peasants between territories. In Bogota, mercados campesinos have been strengthened, which have made it possible to bring food produced by peasants in Tolima, Meta and Boyacá to urban households, promoting short marketing circuits and fair payment to producers. In spite of these alternatives, the demonstrations to make visible the hunger of the households emerged the trapos rojos (red rags) in the houses, which have alerted about the situation of a good part of Colombians and have encouraged solidarity among neighbors. The position of academia has been avant-garde, directly involving peasants in processes to guarantee the right to food in Colombia.

Neurovascular coupling is a fundamental brain mechanism that regulates local cerebral blood flow (CBF) in response to changes in neuronal activity. Functional imaging techniques are commonly used to record these changes in CBF as a proxy of neuronal activity to study the human brain. However, the mechanisms of neurovascular coupling remain incompletely understood. Here we show in experimental animal models (laboratory rats and mice) that the neuronal activity-dependent increases in local CBF in the somatosensory cortex are prevented by saturation of the CO 2 -sensitive vasodilatory brain mechanism with surplus of exogenous CO 2 or disruption of brain CO 2 /HCO 3 - transport by genetic knockdown of electrogenic sodium-bicarbonate cotransporter 1 (NBCe1) expression in astrocytes. A systematic review of the literature data shows that CO 2 and increased neuronal activity recruit the same vasodilatory signaling pathways. These results and analysis suggest that CO 2 mediates signaling between neurons and the cerebral vasculature to regulate brain blood flow in accord with changes in the neuronal activity., (© 2022. The Author(s).)

The onset and mechanisms underlying neurodegenerative diseases remain uncertain. The main features of neurodegenerative diseases have been related with cellular and molecular events like neuronal loss, mitochondrial dysfunction and aberrant accumulation of misfolded proteins or peptides in specific areas of the brain. The most prevalent neurodegenerative diseases belonging to age-related pathologies are Alzheimer's disease, Huntington's disease, Parkinson's disease and amyotrophic lateral sclerosis. Interestingly, mitochondrial dysfunction has been observed to occur during the early onset of several neuropathological events associated to neurodegenerative diseases. The master regulator of mitochondrial quality control and energetic metabolism is the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Additionally, it has been observed that PGC-1α appears to be a key factor in maintaining neuronal survival and synaptic transmission. In fact, PGC-1α downregulation in different brain areas (hippocampus, substantia nigra, cortex, striatum and spinal cord) that occurs in function of neurological damage including oxidative stress, neuronal loss, and motor disorders has been seen in several animal and cellular models of neurodegenerative diseases. Current evidence indicates that PGC-1α upregulation may serve as a potent therapeutic approach against development and progression of neuronal damage. Remarkably, increasing evidence shows that PGC-1α deficient mice have neurodegenerative diseases-like features, as well as neurological abnormalities. Finally, we discuss recent studies showing novel specific PGC-1α isoforms in the central nervous system that appear to exert a key role in the age of onset of neurodegenerative diseases and have a neuroprotective function in the central nervous system, thus opening a new molecular strategy for treatment of neurodegenerative diseases. The purpose of this review is to provide an up-to-date overview of the PGC-1α role in the physiopathology of neurodegenerative diseases, as well as establish the importance of PGC-1α function in synaptic transmission and neuronal survival., Competing Interests: None