No abstract

The GABAergic system is critically involved in the modulation of anxiety levels, and dysfunction of GABAergic neurotransmission appears to be involved in the development of generalized anxiety disorder. Precursor cells from the medial ganglionic eminence (MGE) have the ability to migrate and differentiate into inhibitory GABAergic interneurons after being transplanted into the mouse brain. Thus, transplantation of interneuronal precursor cells derived from the MGE into a postnatal brain could modify the neuronal circuitry, increasing GABAergic tone and decreasing anxiety-like behavior in animals. Our aim was to verify the in vivo effects of transplanted MGE cells by evaluating anxiety-like behavior in mice. MGE cells from 14-day green fluorescent protein (GFP) embryos were transplanted into newborn mice. At 15, 30, and 60 days posttransplant, the animals were tested for anxiety behavior with the elevated plus maze (EPM) test. Our results show that transplanted cells from MGE were able to migrate to different regions of the brain parenchyma and to differentiate into inhibitory interneurons. The neuronal precursor cell transplanted animals had decreased levels of anxiety, indicating a specific function of these cells in vivo. We suggested that transplantation of MGE-derived neuronal precursors into neonate brain could strengthen the inhibitory function of the GABAergic neuronal circuitry related to anxiety-like behavior in mice.

SUMMARYThe distribution of bone marrow cells in brain areas during the acute period after pilocarpine-induced status epilepticus (SE) was investigated here. To achieve this, we generated chimeric mice by engrafting bone marrow cells from enhanced green fluorescent protein (eGFP) transgenic mice. GFP + bone marrow-derived cells were found throughout the brain, predominantly in the hippocampus.As expected, these cells exhibited the characteristics of microglia. The pattern of distribution, proliferation, and differentiation of GFP + cells changes as a function of intensity and time following SE. This pattern is also a consequence of the inflammatory response, which is followed by the progressive neuronal damage that is characteristic of the pilocarpine model.

We conclude that epileptic seizures directly affect vascularization in the hippocampus mediated by bone marrow-derived cells in a time-dependent manner.

We conclude that freshly isolated and neurosphere-grown MGE cells reduced seizures by different mechanisms (inhibitory interneurons vs. astrocytes). Fresh MGE cells appear more appropriate for cell therapies targeting inhibitory interneurons for conferring anticonvulsant outcomes.