https://hdl.handle.net/10259/9895 Thu, 23 Apr 2026 03:22:28 GMT 2026-04-23T03:22:28Z https://hdl.handle.net/10259/9987 Dietary tryptophan depletion alters the faecal bacterial community structure of compulsive drinker rats in schedule-induced polydipsia Merchán Carrillo, Ana; Pérez Fernández, Cristian Antonio; López, María J.; Moreno Casco, José Joaquín; Moreno-Montoya, Margarita; Sánchez Santed, Fernando; Flores, Pilar Rationale: Compulsive behaviour, present in different psychiatric disorders such as obsessive-compulsive disorder, schizophrenia and drug abuse, is associated with altered levels of serotonin (5-hydroxytryptamine, 5-HT). The gut microbiota regulates tryptophan (TRP) metabolism and may affect global 5-H synthesis in the enteric and central nervous systems, suggesting a possible involvement of gut microbiota in compulsive spectrum disorders. Objectives: The present study investigated whether chronic TRP depletion by diet alters the faecal bacterial community profiles of compulsive versus non-compulsive rats in schedule-induced polydipsia (SIP). Peripheral plasma 5-HT and brain-derived neurotrophic factor (BDNF) levels were evaluated. Methods: Wistar rats were selected as High Drinkers (HD) or Low Drinkers (LD) according to their SIP behaviour and were fed for 14 days with either a TRP-free diet (T-) or a TRP-supplemented diet (T+). The faecal bacterial community structure was investigated with 16S rRNA gene-targeted denaturing gradient gel electrophoresis (DGGE) fingerprinting analysis. Results: Compulsive HD rats showed a lower bacterial diversity than LD rats, irrespectively of the diet. The TRP-depleted HD rats, the only group increasing compulsive licking in SIP, showed a reduction of bacterial evenness and a highly functionally organized community compared with the other groups, indicating that this bacterial community is more fragile to external changes due to the dominance of a low number of species. The chronic TRP depletion by diet effectively reduced peripheral plasma 5-HT levels in both HD and LD rats, while plasma BDNF levels were not altered. Conclusions: These results highlight the possible implication of reduced microbial diversity in compulsive behaviour and the involvement of the serotonergic system in modulating the gut brain-axis in compulsive spectrum disorders. Sat, 01 May 2021 00:00:00 GMT https://hdl.handle.net/10259/9987 2021-05-01T00:00:00Z https://hdl.handle.net/10259/9897 Relationship between Autism Spectrum Disorder and Pesticides: A Systematic Review of Human and Preclinical Models Biosca-Brull, Judit; Pérez Fernández, Cristian Antonio; Mora, Santiago; Carrillo, Beatriz; Pinos, Helena; Conejo, Nelida Maria; Collado, Paloma; Arias, Jorge L.; Martín-Sánchez, Fernando; Sánchez Santed, Fernando; Colomina, María Teresa Autism spectrum disorder (ASD) is a complex set of neurodevelopmental pathologies characterized by impoverished social and communicative abilities and stereotyped behaviors. Although its genetic basis is unquestionable, the involvement of environmental factors such as exposure to pesticides has also been proposed. Despite the systematic analyses of this relationship in humans, there are no specific reviews including both human and preclinical models. The present systematic review summarizes, analyzes, and discusses recent advances in preclinical and epidemiological studies. We included 45 human and 16 preclinical studies. These studies focused on Organophosphates (OP), Organochlorine (OC), Pyrethroid (PT), Neonicotinoid (NN), Carbamate (CM), and mixed exposures. Preclinical studies, where the OP Chlorpyrifos (CPF) compound is the one most studied, pointed to an association between gestational exposure and increased ASD-like behaviors, although the data are inconclusive with regard to other ages or pesticides. Studies in humans focused on prenatal exposure to OP and OC agents, and report cognitive and behavioral alterations related to ASD symptomatology. The results of both suggest that gestational exposure to certain OP agents could be linked to the clinical signs of ASD. Future experimental studies should focus on extending the analysis of ASD-like behaviors in preclinical models and include exposure patterns similar to those observed in human studies. Sat, 01 May 2021 00:00:00 GMT https://hdl.handle.net/10259/9897 2021-05-01T00:00:00Z https://hdl.handle.net/10259/8634 Postnatal exposure to low doses of Chlorpyrifos induces long-term effects on 5C-SRTT learning and performance, cholinergic and GABAergic systems and BDNF expression Pérez Fernández, Cristian Antonio; Morales Navas, Miguel; Guardia Escote, Laia; Colomina, María Teresa; Giménez, Estela; Sánchez Santed, Fernando Alterations in attention and inhibitory control are common features in several neurological disorders. Environmental factors such as exposure to pesticides have been linked to their appearance. Chlorpyrifos (CPF) is one of the most widely used organophosphate compounds in the world. CPF exposure during development seems to be critical for later behavioral and molecular disruptions during adult ages, although this depends on the specific period of development, where the preweaning period is one of the least studied. Despite the abundant empirical work made in the last decades on developmental CPF exposure, the systematic study of this on attention is sparse, and nonexistent concerning inhibitory control, without a single study on preweaning developmental stages. The present research explored the effects of the exposure to low doses of CPF that do not elicit a significant inhibition of the Cholinesterases during this developmental period on rats' behavior in the five-choice serial reaction time task. Behavioral manipulations (inter-trial interval and stimulus duration), pharmacological manipulations (cholinergic and GABAergic drugs) and brain gene expression analyses were also conducted. Exposure to CPF decreased the locomotor activity and enhanced the learning profile of the female rats, increased the impulsive rates, unmasked by a longer inter-trial interval, hypo-sensitized the cholinergic system and downregulated the mRNA expression levels of the brain-derived neurotrophic factor in the dorsal striatum of the male rats. This happened without significant inhibition of the brain Acetylcholinesterase. All this new information corroborates that the exposure to a common pesticide at low doses during a key, but under-explored developmental period importantly affects different behaviors, neurotransmitter systems, and molecules that are altered in the main neurological disorders observed nowadays. Sat, 01 Aug 2020 00:00:00 GMT https://hdl.handle.net/10259/8634 2020-08-01T00:00:00Z https://hdl.handle.net/10259/8633 Medium and long-term effects of low doses of Chlorpyrifos during the postnatal, preweaning developmental stage on sociability, dominance, gut microbiota and plasma metabolites Pérez Fernández, Cristian Antonio; Morales Navas, Miguel; Aguilera Sáez, Luis Manuel; Abreu, Ana Cristina; Guardia Escote, Laia; Fernández, Ignacio; Garrido Cárdenas, José Antonio; Colomina, María Teresa; Giménez, Estela; Sánchez Santed, Fernando Autism spectrum disorder (ASD) is a complex neurodevelopmental pathology characterized by altered verbalizations, reduced social interaction behavior, and stereotypies. Environmental factors have been associated with its development. Some researchers have focused on pesticide exposure. Chlorpyrifos (CPF) is the most used Organophosphate. Previous developmental studies with CPF showed decreased, enhanced or no effect on social outcomes eminently in mice. The study of CPF exposure during preweaning stages on social behavior is sparse in mice and non-existent in rats. d stressors could be at the basis of ASD development, and around postnatal day 10 in the rat is equivalent to the human birthday in neurodevelopmental terms. We explored the effects of exposure to low doses (1mg/kg/mL/day) of CPF during this stage regarding: sociability, dominance gut microbiome and plasma metabolomic profile, since alterations in these systems have also been linked to ASD. There was a modest influence of CPF on social behavior in adulthood, with null effects during adolescence. Dominance and hierarchical status were not affected by exposure. Dominance status explained the significant reduction in reaction to social novelty observed on the sociability test. CPF induced a significant gut microbiome dysbiosis and triggered a hyperlipidemic, hypoglycemic/hypogluconeogenesis and a general altered cell energy production in females. These behavioral results in rats extend and complement previous studies with mice and show novel influences on gut metagenomics and plasma lipid profile and metabolomics, but do not stablish a relation between the exposure to CPF and the ASD phenotype. The effects of dominance status on reaction to social novelty have an important methodological meaning for future research on sociability. Fri, 01 May 2020 00:00:00 GMT https://hdl.handle.net/10259/8633 2020-05-01T00:00:00Z