Postnatal Transplantation of Interneuronal Precursor Cells Decreases Anxiety-Like Behavior in Adult Mice

Valente, Maria Fernanda; Romariz, Simone; Calcagnotto, María Elisa; Ruiz, Lorena P.; Mello, Luiz E.; Frussa‐Filho, Roberto; Longo, Beatriz M.

doi:10.3727/096368912x657422

Cited by 13 publications

(16 citation statements)

References 42 publications

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“…Likewise, aggressive behaviors were diminished in epileptic mice that received interneuron transplants to the adult hippocampus, but not the amygdala (32). Moreover, while transplantation to both structures reduced hyperactivity in adult epileptic animals, it did not produce some of the anxiolytic effects observed after transplantation to wild-type neonatal animals (72). This finding could be attributed to differences between the transplant recipients (epileptic versus wild-type), time of transplantation (adult versus neonate), and structures targeted (hippocampus and amygdala versus neocortex).…”

Section: The Clinical Potential Of Interneuron Transplantationmentioning

confidence: 92%

“…At 30 and 60 days after transplantation, but not 15 days, transplant recipients were less likely to avoid exposed areas of an elevated plus maze, a behavior indicative of diminished anxiety (72). Likewise, aggressive behaviors were diminished in epileptic mice that received interneuron transplants to the adult hippocampus, but not the amygdala (32).…”

Section: The Clinical Potential Of Interneuron Transplantationmentioning

confidence: 99%

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Interneurons from Embryonic Development to Cell-Based Therapy

Southwell

Nicholas

Basbaum

et al. 2014

Science

176

180

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Many neurologic and psychiatric disorders are marked by imbalances between neural excitation and inhibition. In the cerebral cortex, inhibition is mediated largely by GABAergic (γ-aminobutyric acid–secreting) interneurons, a cell type that originates in the embryonic ventral telencephalon and populates the cortex through long-distance tangential migration. Remarkably, when transplanted from embryos or in vitro culture preparations, immature interneurons disperse and integrate into host brain circuits, both in the cerebral cortex and in other regions of the central nervous system. These features make interneuron transplantation a powerful tool for the study of neurodevelopmental processes such as cell specification, cell death, and cortical plasticity. Moreover, interneuron transplantation provides a novel strategy for modifying neural circuits in rodent models of epilepsy, Parkinson’s disease, mood disorders, and chronic pain.

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Section: The Clinical Potential Of Interneuron Transplantationmentioning

confidence: 92%

Section: The Clinical Potential Of Interneuron Transplantationmentioning

confidence: 99%

Interneurons from Embryonic Development to Cell-Based Therapy

Southwell

Nicholas

Basbaum

et al. 2014

Science

176

180

View full text Add to dashboard Cite

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“…It will be interesting to investigate whether interneuron transplantation can modify fear memory resiliency, which bears strong therapeutic implications for patients suffering from posttraumatic stress disorders. Interestingly, MGE cell transplants have been shown to reduce anxiety levels in WT animals (Valente et al, 2013). …”

Section: Disease-modifying Properties Of Mge Transplantsmentioning

confidence: 99%

Transplantation of GABAergic interneurons for cell-based therapy

Spatazza

Leon

Alvarez-Buylla

2017

Functional Neural Transplantation IV - Translation to Clinical Application, Part B

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Many neurological disorders stem from defects in or the loss of specific neurons. Neuron transplantation has tremendous clinical potential for central nervous system therapy as it may allow for the targeted replacement of those cells that are lost in diseases. Normally, most neurons are added during restricted periods of embryonic and fetal development. The permissive milieu of the developing brain promotes neuronal migration, neuronal differentiation, and synaptogenesis. Once this active period of neurogenesis ends, the chemical and physical environment of the brain changes dramatically. The brain parenchyma becomes highly packed with neuronal and glial processes, extracellular matrix, myelin, and synapses. The migration of grafted cells to allow them to home into target regions and become functionally integrated is a key challenge to neuronal transplantation. Interestingly, transplanted young telencephalic inhibitory interneurons are able to migrate, differentiate, and integrate widely throughout the postnatal brain. These grafted interneurons can also functionally modify local circuit activity. These features have facilitated the use of interneuron transplantation to study fundamental neurodevelopmental processes including cell migration, cell specification, and programmed neuronal cell death. Additionally, these cells provide a unique opportunity to develop interneuron-based strategies for the treatment of diseases linked to interneuron dysfunction and neurological disorders associated to circuit hyperexcitability.

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“…Neural precursor cells from the medial ganglionic eminence (MGE) of the telencephalic region in the developing brain are responsible for producing most of the inhibitory interneurons in both the cortex and the hippocampus of the mature brain [3, 4]. When transplanted into the newborn cortex, these cells are able to migrate and integrate into the circuitry of the host brain, forming functional synapses that modify the inhibitory input [3–5]. In the central nervous system, GABA-mediated inhibition is critical for controlling synaptic circuits involved in the modulation of anxiety [6].…”

Section: Introductionmentioning

confidence: 99%

“…In the central nervous system, GABA-mediated inhibition is critical for controlling synaptic circuits involved in the modulation of anxiety [6]. Studies evaluating the anxiety behavior of animals transplanted with cells derived from the MGE [5] and LGE (lateral ganglionic eminence) [7] have shown that these cells can produce anxiolytic-like effects.…”

Section: Introductionmentioning

confidence: 99%

Long-lasting anxiolytic effect of neural precursor cells freshly prepared but not neurosphere-derived cell transplantation in newborn rats

et al. 2014

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BackgroundThe GABAergic system plays an important role in modulating levels of anxiety. When transplanted into the brain, precursor cells from the medial ganglionic eminence (MGE) have the ability to differentiate into GABAergic interneurons and modify the inhibitory tone in the host brain. Currently, two methods have been reported for obtaining MGE precursor cells for transplantation: fresh and neurosphere dissociated cells. Here, we investigated the effects generated by transplantation of the two types of cell preparations on anxiety behavior in rats.ResultsWe transplanted freshly dissociated or neurosphere dissociated cells into the neonate brain of male rats on postnatal (PN) day 2–3. At early adulthood (PN 62–63), transplanted animals were tested in the Elevated Plus Maze (EPM). To verify the differentiation and migration pattern of the transplanted cells in vitro and in vivo, we performed immunohistochemistry for GFP and several interneuron-specific markers: neuropeptide Y (NPY), parvalbumin (PV) and calretinin (CR). Cells from both types of preparations expressed these interneuronal markers. However, an anxiolytic effect on behavior in the EPM was observed in animals that received the MGE-derived freshly dissociated cells but not in those that received the neurosphere dissociated cells.ConclusionOur results suggest a long-lasting anxiolytic effect of transplanted freshly dissociated cells that reinforces the inhibitory function of the GABAergic neuronal circuitry in the hippocampus related to anxiety-like behavior in rats.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2202-15-94) contains supplementary material, which is available to authorized users.

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Postnatal Transplantation of Interneuronal Precursor Cells Decreases Anxiety-Like Behavior in Adult Mice

Cited by 13 publications

References 42 publications

Interneurons from Embryonic Development to Cell-Based Therapy

Interneurons from Embryonic Development to Cell-Based Therapy

Transplantation of GABAergic interneurons for cell-based therapy

Long-lasting anxiolytic effect of neural precursor cells freshly prepared but not neurosphere-derived cell transplantation in newborn rats

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