How the forebrain transitions to adulthood: developmental plasticity markers in a long-lived rodent reveal region diversity and the uniqueness of adolescence.

Maturation of the forebrain involves transitions from higher to lower levels of synaptic plasticity. The timecourse of these changes likely differs between regions, with the stabilization of some networks scaffolding the development of others. To gain better insight into neuroplasticity changes associated with maturation to adulthood, we examined the distribution of two molecular markers for developmental plasticity. We conducted the examination on male and female degus (Octodon degus), a rodent species with a relatively long developmental timecourse that offers a promising model for studying both development and age-related neuropathology. Immunofluorescent staining was used to measure perineuronal nets (PNNs), an extracellular matrix structure that emerges during the closure of critical plasticity periods, as well as microglia, resident immune cells that play a crucial role in synapse remodeling during development. PNNs (putatively restricting plasticity) were found to be higher in non-juvenile (>3 month) degus, while levels of microglia (putatively mediating plasticity) decreased across ages more gradually, and with varying timecourses between regions. Degus also showed notable variation in PNN levels between cortical layers and hippocampal subdivisions that have not been previously reported in other species. These results offer a glimpse into neuroplasticity changes occurring during degu maturation and highlight adolescence as a unique phase of neuroplasticity, in which PNNs have been established but microglia remain relatively high.

First International Conference on Unconventional Animal Models of Alzheimer's Disease and Aging.

The first International Conference on Unconventional Animal Models of Alzheimer's Disease and Aging (UAMAA) took place on December 13-16, 2023, in Santiago, Chile. The Alzheimer's disease (AD) research field is currently in search for new and unconventional models that could hold greater translational potential than transgenic mouse models. Thus this UAMAA conference is timely and significant. The event consisted of 6 sessions with talks from 28 world-class scientists from all over the world. These animal models of interest include the degu (Octodon degu), the dog (Canis familiaris), and certain species of nonhuman primates that may better recapitulate neuropathology and cognitive impairments in human AD. Our conference has provided a formal forum to discuss and highlight new research directions, alternative animal models, and innovative approaches for the AD and aging research field.

Anatomical and molecular characterization of parvalbumin-cholecystokinin co-expressing inhibitory interneurons: implications for neuropsychiatric conditions.

Inhibitory interneurons are crucial to brain function and their dysfunction is implicated in neuropsychiatric conditions. Emerging evidence indicates that cholecystokinin (CCK)-expressing interneurons (CCK+) are highly heterogenous. We find that a large subset of parvalbumin-expressing (PV+) interneurons express CCK strongly; between 40 and 56% of PV+ interneurons in mouse hippocampal CA1 express CCK. Primate interneurons also exhibit substantial PV/CCK co-expression. Mouse PV+/CCK+ and PV+/CCK- cells show distinguishable electrophysiological and molecular characteristics. Analysis of single nuclei RNA-seq and ATAC-seq data shows that PV+/CCK+ cells are a subset of PV+ cells, not of synuclein gamma positive (SNCG+) cells, and that they strongly express oxidative phosphorylation (OXPHOS) genes. We find that mitochondrial complex I and IV-associated OXPHOS gene expression is strongly correlated with CCK expression in PV+ interneurons at both the transcriptomic and protein levels. Both PV+ interneurons and dysregulation of OXPHOS processes are implicated in neuropsychiatric conditions, including autism spectrum (ASD) disorder and schizophrenia (SCZ). Analysis of human brain samples from patients with these conditions shows alterations in OXPHOS gene expression. Together these data reveal important molecular characteristics of PV-CCK co-expressing interneurons and support their implication in neuropsychiatric conditions.

Cognitively impaired aged Octodon degus recapitulate major neuropathological features of sporadic Alzheimer's disease.

The long-lived Chilean rodent (Octodon degus) has been reported to show spontaneous age-dependent neuropathology and cognitive impairments similar to those observed in human AD. However, the handful of published papers on degus of differing genetic backgrounds yield inconsistent findings about sporadic AD-like pathological features, with notably differing results between lab in-bred degus versus outbred degus. This motivates more extensive characterization of spontaneously occurring AD-like pathology and behavior in degus. In the present study, we show AD-like neuropathological markers in the form of amyloid deposits and tau abnormalities in a cognitively impaired subset of aged outbred degus. Compared to the aged degus that show normal burrowing behavior, the age-matched degus with burrowing behavior deficits correlatively exhibit detectable human AD-like Aß deposits and tau neuropathology, along with neuroinflammatory markers that include enhanced microglial activation and higher numbers of reactive astrocytes in the brain. This subset of cognitively impaired aged degus also exhibits cerebral amyloid angiopathy and tauopathy. We find robust neurodegenerative features in behaviorally deficient aged degus, including hippocampal neuronal loss, altered parvalbumin and perineuronal net staining in the cortex, and increased c-Fos neuronal activation in the cortex that is consistent with the neural circuit hyperactivity reported in human AD patients. By focusing on the subset of aged degus that show AD-like behavioral deficits and correlative neuropathology, our findings establish outbred degus as a natural model of sporadic AD and demonstrate the potential importance of wild-type outbred genetic backgrounds for AD pathogenesis.

Genome Sequencing Variations in the Octodon degus, an Unconventional Natural Model of Aging and Alzheimer's Disease.

The degu (Octodon degus) is a diurnal long-lived rodent that can spontaneously develop molecular and behavioral changes that mirror those seen in human aging. With age some degu, but not all individuals, develop cognitive decline and brain pathology like that observed in Alzheimer's disease including neuroinflammation, hyperphosphorylated tau and amyloid plaques, together with other co-morbidities associated with aging such as macular degeneration, cataracts, alterations in circadian rhythm, diabetes and atherosclerosis. Here we report the whole-genome sequencing and analysis of the degu genome, which revealed unique features and molecular adaptations consistent with aging and Alzheimer's disease. We identified single nucleotide polymorphisms in genes associated with Alzheimer's disease including a novel apolipoprotein E (Apoe) gene variant that correlated with an increase in amyloid plaques in brain and modified the in silico predicted degu APOE protein structure and functionality. The reported genome of an unconventional long-lived animal model of aging and Alzheimer's disease offers the opportunity for understanding molecular pathways involved in aging and should help advance biomedical research into treatments for Alzheimer's disease.

Health status alterations in Ruditapes philippinarum after continuous secondary effluent exposure before and after additional tertiary treatment application.

A mobile pilot plant was set up in a wastewater treatment plant (WWTP) in southwest Spain to address potential adverse effects of effluents as a whole contaminant, which are discharging into marine environments. Ruditapes philippinarum specimens were exposed to different effluent concentrations (50%, 25%, 12.5%, 6.25%, and 3.15%) during seven days. After effluent exposure, lysosomal membrane stability alterations (LMS), changes in the energy status storage (total lipids content (TLP) and in the mitochondrial electron transport (MET), inhibition of inflammatory mechanisms (cyclooxygenase activity (COX)), and neurotoxic effects (acetylcholinesterase (AChE) were determined in exposed organisms. Furthermore, potential toxic reduction in the effluent was analysed by the application of an additional microalgae tertiary treatment called photobiotreatment (PhtBio). Results after PhtBio confirmed the toxic effect reduction in exposed organisms. Neuroendocrine effects, alterations in energy budget and in lipid storage revealed alterations in clam's health status causing stress conditions after effluent exposure.

Biochemical responses of Solea senegalensis after continuous flow exposure to urban effluents.

Urban effluent potential toxicity was assessed by a battery of biomarkers aimed at determining sub-lethal effects after continuous exposure on the marine organism Solea senegalensis. Specimens were exposed to five effluent concentrations (1/2, 1/4, 1/8, 1/16, 1/32) during 7-days, simulating the dispersion plume at the discharge point. Three different groups of biomarkers were selected in the present study: biomarkers of exposure (Phase I: EROD and DBF; Phase II: GST), biomarkers with antioxidant responses (GR and GPX) and biomarkers of effects (DNA damage and LPO). Additionally, a biological depuration treatment (photobiotreatment (PhtBio)) was tested in order to reduce the adverse effects on aquatic organisms. Effluent exposure caused sub-lethal responses in juvenile fish suggesting oxidative stress. After PhtBio application, concentrations of the major part of measured contaminants were reduced, as well as their bioavailability and adverse effects.

Environmental risk assessment of effluents as a whole emerging contaminant: Efficiency of alternative tertiary treatments for wastewater depuration.

Emerging contaminants (ECs) and regulated compounds (RCs) from three different WWTP effluents were measured in the current study. The efficiency of two tertiary treatments, Photobiotreatment (PhtBio) and Multi-Barrier Treatment (MBT), for removing contaminants was determined. Results indicated different percentages of removal depending on the treatment and the origin of the effluent. Risk Quotients (RQs) were determined for different species of algae, Daphnia, and fish. RQ results revealed diverse risk values depending on the bioindicator species. Tonalide, galaxolide (fragrances), and ofloxacin (antibiotic) were the most persistent and harmful substances in tested effluents. "Negligible risk" category was reached since a wide diversity of ECs were removed by MBT with high removal percentages. Contrarily, PhtBio was effective only in the depuration of certain chemical compounds, and its efficiency depended on the composition of the raw effluent.

Are combined AOPs effective for toxicity reduction in receiving marine environment? Suitability of battery of bioassays for wastewater treatment plant (WWTP) effluent as an ecotoxicological assessment.

Ecotoxicological assessment of three different wastewater treatment plant (WWTP) effluents D1, D2 and D3 was performed before and after tertiary treatment using combination of advanced oxidation processes (AOPs). A multibarrier treatment (MBT) consisting of microfiltration (MF), hydrogen peroxide photolysis (H2O2/UVC) and catalytic wet peroxide oxidation (CWPO) was applied for all effluents. Sparus aurata, Paracentrotus lividus, Isochrysis galbana and Vibrio fischeri, representing different trophic levels, constituted the battery of bioassays. Different acute toxicity effects were observed in each WWTP effluents tested. The percentage of sea urchin larval development and mortality fish larvae were the most sensitive endpoints. Significant reduction (p < 0.05) of effluent's toxicity was observed using a classification pT-method after MBT process. Base on obtained results, tested battery of bioassays in pT-method framework can be recommended for acute toxicity preliminary evaluation of WWTP effluents for the marine environment.

EGb761 blocks MPP+-induced lipid peroxidation in mouse corpus striatum.

EGb761 has been suggested to be an antioxidant and free radical scavenger. Excess generation of free radicals, leading to lipid peroxidation (LP), has been proposed to play a role in the damage to striatal neurons induced by 1-methyl-4-phenylpyridinium (MPP+). We investigated the effects of EGb761 pretreatment on MPP+ neurotoxicity. C-57 black mice were pretreated with EGb761 for 17 days at different doses (0.63, 1.25, 2.5, 5 or 10 mg/kg) followed by administration of MPP+, (0.18, 0.36 or 0.72 mg/kg). LP was analyzed in corpus striatum at 30 min, 1 h, 2 h and 24 h after MPP+ administration. Striatal dopamine content was analyzed by HPLC at the highest EGb761 dose at 2 h and 24 h after MPP+ administration. MPP+-induced LP was blocked (100%) by EGb761 (10 mg/kg). Pretreatment with EGb761 partially prevented (32%) the dopamine-depleting effect of MPP+ at 24 h. These results suggest that supplements of EGb761 may be effective at preventing MPP+-induced oxidative stress.

Características de la mordedura por perros, en niños atendidos en un servicio médico de urgencias del Centro Médico "La Raza" / Characteristics of the childre are bitten dog atended in the emergency room in the Centro Medico \"La Raza\"

En el presente estudio se informa acerca de las circunstancias en que son mordidos por can los niños que acuden a una consulta de urgencias de un hospital general. Se estudiaron 63 niños; el sexo masculino predominó en una relación 2:1, los escolares fueron los más afectados con 50 por ciento; la cabeza fue el sitio de la lesión en 38 por ciento; hubo un caso de una mordedura fatal y dos en los párpados. Se comenta la deficiente educación en el cuidado y manejo de los perros que se refleja en el elevado número de aplicaciones de vacuna antirrábica.