Bifidobacterium CECT 7765 modulates early stress-induced immune, neuroendocrine and behavioral alterations in mice.

Emerging evidence suggests that there is a window of opportunity within the early developmental period, when microbiota-based interventions could play a major role in modulating the gut-brain axis and, thereby, in preventing mood disorders. This study aims at evaluating the effects and mode of action of Bifidobacterium pseudocatenulatum CECT 7765 in a murine model of chronic stress induced by maternal separation (MS). C57Bl/6J male breast-fed pups were divided into four groups, which were subjected or not to MS and supplemented with placebo or B. pseudocatenulatum CECT7765 until postnatal period (P) 21 and followed-up until P41. Behavioral tests were performed and neuroendocrine parameters …

Interaction between Angiotensin Type 1, Type 2, and Mas Receptors to Regulate Adult Neurogenesis in the Brain Ventricular–Subventricular Zone

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Social stress during adolescence activates long-term microglia inflammation insult in reward processing nuclei

The experience of social stress during adolescence is associated with higher vulnerability to drug use. Increases in the acquisition of cocaine self-administration, in the escalation of cocaine-seeking behavior, and in the conditioned rewarding effects of cocaine have been observed in rodents exposed to repeated social defeat (RSD). In addition, prolonged or severe stress induces a proinflammatory state with microglial activation and increased cytokine production. The aim of the present work was to describe the long-term effects induced by RSD during adolescence on the neuroinflammatory response and synaptic structure by evaluating different glial and neuronal markers. In addition to an inc…

Influence of massed and distributed context preexposure on contextual fear and Egr-1 expression in the basolateral amygdala

Preexposure to the conditioning context can influence the expression of context-conditioned fear. We used behavioral and early growth response gene (egr-1) assays in rats to study the effects of massed and distributed context preexposure on context-conditioned fear. The results demonstrated that massed context preexposure impaired acquisition of contextual fear, an effect here referred to as delayed shock deficit. Spaced context preexposure produced similar inhibitory effects. Significantly, the introduction of a brief change of context prior to conditioning completely reversed the deficit induced by massed, but not by distributed, context preexposure. This reversibility was inversely relat…

Lewy body extracts from Parkinson disease brains trigger α-synuclein pathology and neurodegeneration in mice and monkeys

Objective Mounting evidence suggests that α-synuclein, a major protein component of Lewy bodies (LB), may be responsible for initiating and spreading the pathological process in Parkinson disease (PD). Supporting this concept, intracerebral inoculation of synthetic recombinant α-synuclein fibrils can trigger α-synuclein pathology in mice. However, it remains uncertain whether the pathogenic effects of recombinant synthetic α-synuclein may apply to PD-linked pathological α-synuclein and occur in species closer to humans. Methods Nigral LB-enriched fractions containing pathological α-synuclein were purified from postmortem PD brains by sucrose gradient fractionation and subsequently inoculate…

Behavioral evaluation of aging in experimental animals

Abstract Since aging is a very a complex multisystemic process, behavioral assessment must cover a combined panoply of physical and neural functions. Behavioral measures must be objective and reproducible to be able to compare between individuals of different ages or experimental conditions. In this chapter, we discuss how aging is reflected in a very variable way in different physical, cognitive, emotional, social, motor, and sensory behaviors. We suggest specific tests to evaluate each of these functions in mice, discussing previous results obtained in different genetic strains. Finally, we identify the most distorting variables to consider, such as age range, gender, or body weight, to m…

Dlk1 dosage regulates hippocampal neurogenesis and cognition

Significance Generation of new neurons occurs normally in the adult brain in two locations: the subventricular zone (SVZ) in the walls of the lateral ventricles and the subgranular zone (SGZ) in the dentate gyrus (DG) of the hippocampus. Neurogenesis in the adult hippocampus has been implicated in cognitive functions such as learning, memory, and recovery of stress response. Imprinted genes are highly prevalent in the brain and have adult and developmental important functions. Genetic deletion of the imprinted gene Dlk1 from either parental allele shows that DLK1 is a key mediator of quiescence in adult hippocampal NSCs. Additionally, Dlk1 is exquisitely dosage sensitive in the brain with p…

The effect of long context exposure on cued conditioning and c-fos expression in the rat forebrain

The c-fos expression was used to study the neural substrates of the cued fear conditioning acquisition, preceded by a short exposure versus a long exposure to the conditioning context. A long-context exposure (either during the night or during the day) prior to conditioning, was associated with low freezing in the learning test. Differences in the c-fos expression of CA1, CA3, BL Amygdala, LS and BNST were found between the short- or long-context groups with a pre-exposure before cued conditioning. Ce Amygdala showed no differences in the c-fos expression labeling. We reported the hippocampal c-fos activation during the cued fear conditioning acquisition. Specifically, the CA1 activation co…

PBX1 acts as terminal selector for olfactory bulb dopaminergic neurons

15 páginas, 8 figuras. Supplementary information available online at http://dev.biologists.org/lookup/doi/10.1242/dev.186841.supplemental

Regulation of the p19(Arf)/p53 pathway by histone acetylation underlies neural stem cell behavior in senescence-prone SAMP8 mice.

Brain aging is associated with increased neurodegeneration and reduced neurogenesis. B1/neural stem cells (B1-NSCs) of the mouse subependymal zone (SEZ) support the ongoing production of olfactory bulb interneurons, but their neurogenic potential is progressively reduced as mice age. Although age-related changes in B1-NSCs may result from increased expression of tumor suppressor proteins, accumulation of DNA damage, metabolic alterations, and microenvironmental or systemic changes, the ultimate causes remain unclear. Senescence-accelerated-prone mice (SAMP8) relative to senescence-accelerated-resistant mice (SAMR1) exhibit signs of hastened senescence and can be used as a model for the stud…

Book review

Physiological Interactions between Microglia and Neural Stem Cells in the Adult Subependymal Niche

Microglia are the prototypical innate immune cells of the central nervous system. They constitute a unique type of tissue-resident mononuclear phagocytes which act as glial cells. Elegant experiments in the last few years have revealed the origin, extraordinary molecular diversity, and phenotypic plasticity of these cells and how their potential relates to both immune and non-immune actions in the normal and diseased brain. Microglial cells originate in the yolk sac and colonize the brain during embryogenesis, playing a role in neural development and later in adult brain function. Neurogenesis continues after birth in discrete areas of the mammalian brain sustained by the postnatal persiste…

Endothelial NT-3 Delivered by Vasculature and CSF Promotes Quiescence of Subependymal Neural Stem Cells through Nitric Oxide Induction

SummaryInteractions of adult neural stem cells (NSCs) with supportive vasculature appear critical for their maintenance and function, although the molecular details are still under investigation. Neurotrophin (NT)-3 belongs to the NT family of trophic factors, best known for their effects in promoting neuronal survival. Here we show that NT-3 produced and secreted by endothelial cells of brain and choroid plexus capillaries is required for the quiescence and long-term maintenance of NSCs in the mouse subependymal niche. Uptake of NT-3 from irrigating vasculature and cerebrospinal fluid (CSF) induces the rapid phosphorylation of endothelial nitric oxide (NO) synthase present in the NSCs, lea…

Synaptic Regulator α-Synuclein in Dopaminergic Fibers Is Essentially Required for the Maintenance of Subependymal Neural Stem Cells.

Synaptic protein -synuclein (-SYN) modulates neurotransmission in a complex and poorly understood manner and aggregates in the cytoplasm of degenerating neurons in Parkinsons disease. Here, we report that -SYN present in dopaminergic nigral afferents is essential for the normal cycling and maintenance of neural stem cells (NSCs) in the brain subependymal zone of adult male and female mice. We also showthat premature senescence of adult NSCs into non-neurogenic astrocytes in mice lacking-SYN resemblesthe effects of dopaminergic fiber degeneration resulting from chronic exposure to 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine or intranigral inoculation of aggregated toxic -SYN. Interestingly…

Inhibition of adult hippocampal neurogenesis disrupts contextual learning but spares spatial working memory, long-term conditional rule retention and spatial reversal.

Neurogenesis in the adult dentate gyrus (DG) of the hippocampus has been implicated in neural plasticity and cognition but the specific functions contributed by adult-born neurons remain controversial. Here, we have explored the relationship between adult hippocampal neurogenesis and memory function using tasks which specifically require the participation of the DG. In two separate experiments several groups of rats were exposed to fractionated ionizing radiation (two sessions of 7 Gy each on consecutive days) applied either to the whole brain or focally, aiming at a region overlying the hippocampus. The immunocytochemical assays showed that the radiation significantly reduced the expressio…

BDNF is essentially required for the early postnatal survival of nociceptors

AbstractNeurotrophins promote the survival of specific types of neurons during development and ensure proper maintenance and function of mature responsive neurons. Significant effects of BDNF (Brain-Derived Neurotrophic Factor) on pain physiology have been reported but the contribution of this neurotrophin to the development of nociceptors has not been investigated. We present evidence that BDNF is required for the survival of a significant fraction of peptidergic and non-peptidergic nociceptors in dorsal root ganglia (DRG) postnatally. Bdnf homozygous mutant mice lose approximately half of all nociceptive neurons during the first 2 weeks of life and adult heterozygotes exhibit hypoalgesia …

Paracrine regulation of neural stem cells in the subependymal zone.

Stem cells maintain their self-renewal and multipotency capacities through a self-organizing network of transcription factors and intracellular pathways activated by extracellular signaling from the microenvironment or "niche" in which they reside in vivo. In the adult mammalian brain new neurons continue to be generated throughout life of the organisms and this lifelong process of neurogenesis is supported by a reservoir of neural stem cells in the germinal regions. The discovery of adult neurogenesis in the mammalian brain has sparked great interest in defining the conditions that guide neural stem cell (NSC) maintenance and differentiation into the great variety of neuronal and glial sub…