Intracerebral adult stem cells transplantation increases brain-derived neurotrophic factor levels and protects against phencyclidine-induced social deficit in mice.

Stem cell-based regenerative therapy is considered a promising cellular therapeutic approach for the patients with incurable brain diseases. Mesenchymal stem cells (MSCs) represent an attractive cell source for regenerative medicine strategies for the treatment of the diseased brain. Previous studies have shown that these cells improve behavioral deficits in animal models of neurological disorders such as Parkinson's and Huntington's diseases. In the current study, we examined the capability of intracerebral human MSCs transplantation (medial pre-frontal cortex) to prevent the social impairment displayed by mice after withdrawal from daily phencyclidine (PCP) administration (10 mg kg(-1) daily for 14 days). Our results show that MSCs transplantation significantly prevented the PCP-induced social deficit, as assessed by the social preference test. In contrast, the PCP-induced social impairment was not modified by daily clozapine treatment. Tissue analysis revealed that the human MSCs survived in the mouse brain throughout the course of the experiment (23 days). Significantly increased cortical brain-derived neurotrophic factor levels were observed in the MSCs-treated group as compared with sham-operated controls. Furthermore, western blot analysis revealed that the ratio of phosphorylated Akt to Akt was significantly elevated in the MSCs-treated mice compared with the sham controls. Our results demonstrate that intracerebral transplantation of MSCs is beneficial in attenuating the social deficits induced by sub-chronic PCP administration. We suggest a novel therapeutic approach for the treatment of schizophrenia-like negative symptoms in animal models of the disorder.

Recuperación de la habilidad motora mediante trasplantes neurales en ratas adultas con lesión de la corteza frontal / Motor skill recovery through neural transplants in adult rats with frontal cortex damage

Objetivo: Investigar los mecanismos involucrados en la recuperación funcional de alteraciones motoras producidas por la lesión de la corteza frontal mediante trasplantes neurales embrionarios, en ratas adultas. Material y metodología: Utilizamos ratas machos, de raza Wistar, empleando pruebas conductuales, métodos electrofisiológicos y técnicas inmunohistoquímicas e histológicas. Los animales se condicionaron en un test motor específico de habilidad motora fina y se determinó su mano preferente. Se realizó una lesión en la corteza frontal contralateral a la mano preferente y se evaluó la efectividad de la lesión mediante el test de conducta. En un grupo de animales lesionados se trasplantó tejido cortical embrionario en la cavidad producida por la lesión; en un segundo grupo, se utilizó tejido fetal amigdalino como tejido donante; y en un tercer grupo, se trasplantó nervio ciático de rata adulta. Los tres grupos se compararon con un grupo de animales control. Resultados: A los tres meses post-trasplante, los animales con trasplantes de tejido fetal amigdalino y con trasplantes de tejido cortical mejoraron el déficit motor producido por la lesión. Los animales con trasplantes de nervio ciático no presentaron ninguna mejoría. Conclusión: Los trasplantes de tejido amigdalino inducen una mejoría similar a la obtenida con los trasplantes de tejido cortical. El origen ontogenético, en parte común, del tejido amigdalino y el tejido cortical podría estar implicado en los mecanismos subyacentes a la recuperación funcional (AU)

Objetive: To investigate the mechanisms by which neural transplants contribute to functional recovery of the motor disorders produced by frontal cortex damage in adult rats. Material and methods: Male Wistar rats were used, with the application of behavioral tests, electrophysiological methods and immunohistochemical and histological techniques. The animals were conditioned using a specific fine motor skill test, with determination of the dominant paw. Damage was produced in the frontal cortex contralateral to the dominant paw, with evaluation of the effectiveness of the lesion based on the behavioral test. In one group of damaged animals embryonic cortical tissue was implanted in the cavity left by the lesion. In a second group fetal amygdaline tissue was used as donor material, while in a third group adult rat sciatic nerve was implanted. The three groups were compared with a control group. Results: Three months after grafting, the rats with fetal amygdaline tissue and with transplanted cortical material improved of the motor defect induced by the lesion. The rats with grafted sciatic nerve showed no improvement. Conclusion: Amygdaline tissue grafts induce improvement similar to that recorded with cortical tissue transplants. The partially shared ontogenetic origin of amygdaline and cortical tissue could be implicated in the functional recovery mechanisms (AU)