Adult-born neurons maintain hippocampal cholinergic inputs and support working memory during aging.

Adult neurogenesis is reduced during aging and impaired in disorders of stress, memory, and cognition though its normal function remains unclear. Moreover, a systems level understanding of how a small number of young hippocampal neurons could dramatically influence brain function is lacking. We examined whether adult neurogenesis sustains hippocampal connections cumulatively across the life span. Long-term suppression of neurogenesis as occurs during stress and aging resulted in an accelerated decline in hippocampal acetylcholine signaling and a slow and progressing emergence of profound working memory deficits. These deficits were accompanied by compensatory reorganization of cholinergic dentate gyrus inputs with increased cholinergic innervation to the ventral hippocampus and recruitment of ventrally projecting neurons by the dorsal projection. While increased cholinergic innervation was dysfunctional and corresponded to overall decreases in cholinergic levels and signaling, it could be recruited to correct the resulting memory dysfunction even in old animals. Our study demonstrates that hippocampal neurogenesis supports memory by maintaining the septohippocampal cholinergic circuit across the lifespan. It also provides a systems level explanation for the progressive nature of memory deterioration during normal and pathological aging and indicates that the brain connectome is malleable by experience.

Effects of taurine supplementation and swimming, associated or not, on obesity and glucose homeostasis in mice / Efeito da suplementação com taurina e da natação, associadas ou não, sobre a obesidade e homeostase glicêmica em camundongos

Studies show that physical exercise (PE) is associated with a reduced fat accumulation and increased insulin sensitivity, and taurine (TAU) improves glucose homeostasis in lean rodents. The aim in this work was evaluate the effects of supplementing TAU and practice of PE, associated or not, on obesity and glucose homeostasis on obese MSG-mice. Neonate male Swiss mice received injections of monosodium glutamate (MSG group) or saline (CON group). From the 30th to the 90th day of life, one group of animals received TAU in drinking water (MSG TAU group), another was subjected to PE (MSG PE group) and a third group underwent both procedures (MSG PE TAU group). Mice treated with MSG become obese, hypertriglyceridemic, glucose intolerant and insulin resistant. The supplementation with TAU and the PE, isolated or associated, reduced the triglycerides (38%), glucose intolerance (around 30%) and KITT (79%) in MSG-obese animals, but did not influence the accumulation of fat. Interestingly, the combination of both strategies significantly reduced the insulin resistance, compared to animals subjected to isolated strategies. In conclusion, the supplementation with TAU and PE, isolated or associated, did not influence the accumulation of fat in MSG-obese mice, however, reduce the triglycerides and insulin resistance.

O exercício físico (EF) está associado à redução do acúmulo de gordura e aumento na sensibilidade à insulina e a taurina (TAU) melhora a homeostase glicêmica em roedores magros. Objetivou-se avaliar os efeitos da suplementação com TAU e do EF, associados ou não, sobre a obesidade e a homeostase glicêmica em camundongos obesos-MSG. Camundongos Swiss machos neonatos receberam injeções de glutamato monossódico (grupo MSG) ou salina (grupo CON). Do 30º ao 90º dia de vida, um grupo de animais MSG recebeu TAU na água de beber (MSG TAU); outro foi submetido ao EF (MSG EX) e um terceiro grupo foi submetido aos dois procedimentos (MSG EX TAU). Camundongos -MSG tornaram-se obesos, hipertrigliceridêmicos, intolerantes à glicose e resistentes à insulina. A suplementação com TAU e o EF, associados ou isolados, reduziram a trigliceridemia (38%), a intolerância à glicose (30%) e o KITT (79%) nos animais obesos-MSG, porém, não influenciaram o acúmulo de gordura. A associação das duas estratégias diminui significativamente a resistência à insulina, comparado aos animais submetidos às estratégias isoladas. Conclui-se que a suplementação com TAU e o EF, associados ou isolados, não influenciam no acúmulo de gordura dos camundongos obesos-MSG, porém, diminuem a trigliceridemia e a resistência à insulina.

Modeling treatment-resistant depression.

Depression is a polygenic and highly complex psychiatric disorder that is currently a major burden on society. Depression is highly heterogeneous in presentation and frequently exhibits high comorbidity with other psychiatric and somatic disorders. Commonly used treatments, such as selective serotonin reuptake inhibitors (SSRIs), are not ideal since only a subset of patients achieve remission. In addition, the reason why some individuals respond to SSRIs while others don't are unknown. Here we begin to ask what the basis of treatment resistance is, and propose new strategies to model this phenomenon in animals. We focus specifically on animal models that offer the appropriate framework to study treatment resistance with face, construct and predictive validity.

Tio2-dopamine complex implanted unilaterally in the caudate nucleus improves motor activity and behavior function of rats with induced hemiparkinsonism.

Parkinson's disease (PD) is characterized by malfunction of dopaminergic systems, and the current symptomatic treatment is to replace lost dopamine. For investigating mechanisms of pathogenesis and alternative treatments to compensate lack of dopamine (DA) activity in PD, the 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD has been useful, these animals display apomorphine-induced contralateral rotational behavior, when they are examined after lesion. The purpose of this study was to assess Titania-dopamine (TiO2-DA) complexes implanted on the caudate nucleus for diminishing motor behavior alterations of the 6-OHDA rat model. Rats with 6-OHDA unilateral lesions received TiO2 alone or TiO2-DA implants, and were tested for open field (OF) gross motor crossing and rearing behaviors, and apomorphine-induced rotation (G) behavior. TiO2 complex have no effects on rearing OF and G behaviors, and a significant reducing effect on crossing motor behavior of normal rats compared to control non-treated rats throughout 56 days of observation. Interestingly, TiO2-DA treatment significant recovered motor crossing and rearing behaviors in 6-OHDA-lesioned rats, and diminished the G behaviors during 56 days of examination. Additionally, in the 6-OHDA-lesioned rats TiO2 treatment had a moderate recovering effect only on crossing behavior compared to lesioned non treated rats. Our results suggest that continuous release of dopamine in the caudate nucleus from TiO2-DA complex is capable of reversing gross motor deficits observed in the 6-OHDA-lesioned rat model of PD. Thistype of delivery system of DA represents a promising therapy for PD in humans.