Patients suffering from Parkinson's disease (PD) display cognitive and neuropsychiatric dysfu... more Patients suffering from Parkinson's disease (PD) display cognitive and neuropsychiatric dysfunctions, especially with disease progression. Although these impairments have been reported to impact more heavily upon a patient's quality of life than any motor dysfunctions, there are currently no interventions capable of adequately targeting these non-motor deficits. Utilizing a rodent model of PD, we investigated whether cell replacement therapy, using intrastriatal transplants of human-derived ventral mesencephalic (hVM) grafts, could alleviate cognitive and neuropsychiatric, as well as motor, dysfunctions. Rats with unilateral 6-hydroxydopamine lesions to the medial forebrain bundle were tested on a complex operant task that dissociates motivational, visuospatial and motor impairments sensitive to the loss of dopamine. A subset of lesioned rats received intrastriatal hVM grafts of ~9weeks gestation. Post-graft, rats underwent repeated drug-induced rotation tests and were teste...
In a previous study we evaluated the conditions under which septal grafts could ameliorate perfor... more In a previous study we evaluated the conditions under which septal grafts could ameliorate performance of rats with fimbria-fornix lesions in an operant differential reinforcement of low rates of responding (DRL) task. Although the best recovery was demonstrated by the group in which the grafts were made 10 days following the lesion surgery, this factor (lesion-graft interval) was confounded with the developmental stage of the donor tissue, and it was suggested that the age of the embryonic donor was a more significant factor than the lesion graft interval in achieving good recovery. The present study provides a better control of embryonic age of the donor tissues, and we report that cholinergic rich septal grafts implanted into the host hippocampus either immediately or 11 days following fimbria-fornix lesion yielded better recovery than when the grafts were implanted after longer (8 weeks) lesion-graft intervals. In addition, grafts implanted into the intact hippocampus were witho...
Grafts of embryonic striatal primordia are able to elicit behavioural recovery in rats which have... more Grafts of embryonic striatal primordia are able to elicit behavioural recovery in rats which have received an excitotoxic lesion to the striatum, and it is believed that the P zones or striatal-like tissue within the transplants play a crucial role in these functional effects. We performed this study to compare the effects of different donor stage of embryonic tissue on
A small diameter positron emission tomography (PET) scanner has been used to monitor [11C]raclopr... more A small diameter positron emission tomography (PET) scanner has been used to monitor [11C]raclopride (D2 receptor) binding in vivo in either intact striatum, denervated striatum following an excitotoxic lesion with ibotenic acid, or lesioned and grafted striatum following implantation of cortical or striatal tissue grafts in rats. Binding of [11C]raclopride was localized in the intact striatum within 20 min of injection of the radioligand, and was much reduced within the lesioned striatum. Cortical grafts exhibited a similar low level of binding to the lesioned striatum, whereas striatal grafts showed specific binding at an intermediate level. The [11C]raclopride binding signal in vivo correlated well with the extent of surviving or grafted striatal tissue observed post morten by Nissl staining and acetylcholinesterase histochemistry. Thus, the distribution of dopamine receptors as seen in the PET scanner are consistent with post mortem anatomical observations of striatal, lesion and graft sizes, and suggest that PET can provide a useful tool for monitoring the viability of implanted striatal graft tissues in vivo.
Rats were trained on an operant task and then received striatal lesions and grafts. Grafts were d... more Rats were trained on an operant task and then received striatal lesions and grafts. Grafts were derived either from whole-ganglionic eminences or restricted to the lateral eminence. When retested 4 months later; graft-associated behavioural recovery was only apparent with extensive retesting. There was no difference in performance between rats that received whole-dissection or lateral-dissection grafts, and no correlation between performance and the amount of striatal-like (P-zone) tissue within the graft. It is suggested that P-zone reconstruction may be necessary, but not sufficient for behavioural recovery, which may additionally depend upon rehabilitative training.
Patients suffering from Parkinson's disease (PD) display cognitive and neuropsychiatric dysfu... more Patients suffering from Parkinson's disease (PD) display cognitive and neuropsychiatric dysfunctions, especially with disease progression. Although these impairments have been reported to impact more heavily upon a patient's quality of life than any motor dysfunctions, there are currently no interventions capable of adequately targeting these non-motor deficits. Utilizing a rodent model of PD, we investigated whether cell replacement therapy, using intrastriatal transplants of human-derived ventral mesencephalic (hVM) grafts, could alleviate cognitive and neuropsychiatric, as well as motor, dysfunctions. Rats with unilateral 6-hydroxydopamine lesions to the medial forebrain bundle were tested on a complex operant task that dissociates motivational, visuospatial and motor impairments sensitive to the loss of dopamine. A subset of lesioned rats received intrastriatal hVM grafts of ~9weeks gestation. Post-graft, rats underwent repeated drug-induced rotation tests and were teste...
In a previous study we evaluated the conditions under which septal grafts could ameliorate perfor... more In a previous study we evaluated the conditions under which septal grafts could ameliorate performance of rats with fimbria-fornix lesions in an operant differential reinforcement of low rates of responding (DRL) task. Although the best recovery was demonstrated by the group in which the grafts were made 10 days following the lesion surgery, this factor (lesion-graft interval) was confounded with the developmental stage of the donor tissue, and it was suggested that the age of the embryonic donor was a more significant factor than the lesion graft interval in achieving good recovery. The present study provides a better control of embryonic age of the donor tissues, and we report that cholinergic rich septal grafts implanted into the host hippocampus either immediately or 11 days following fimbria-fornix lesion yielded better recovery than when the grafts were implanted after longer (8 weeks) lesion-graft intervals. In addition, grafts implanted into the intact hippocampus were witho...
Grafts of embryonic striatal primordia are able to elicit behavioural recovery in rats which have... more Grafts of embryonic striatal primordia are able to elicit behavioural recovery in rats which have received an excitotoxic lesion to the striatum, and it is believed that the P zones or striatal-like tissue within the transplants play a crucial role in these functional effects. We performed this study to compare the effects of different donor stage of embryonic tissue on
A small diameter positron emission tomography (PET) scanner has been used to monitor [11C]raclopr... more A small diameter positron emission tomography (PET) scanner has been used to monitor [11C]raclopride (D2 receptor) binding in vivo in either intact striatum, denervated striatum following an excitotoxic lesion with ibotenic acid, or lesioned and grafted striatum following implantation of cortical or striatal tissue grafts in rats. Binding of [11C]raclopride was localized in the intact striatum within 20 min of injection of the radioligand, and was much reduced within the lesioned striatum. Cortical grafts exhibited a similar low level of binding to the lesioned striatum, whereas striatal grafts showed specific binding at an intermediate level. The [11C]raclopride binding signal in vivo correlated well with the extent of surviving or grafted striatal tissue observed post morten by Nissl staining and acetylcholinesterase histochemistry. Thus, the distribution of dopamine receptors as seen in the PET scanner are consistent with post mortem anatomical observations of striatal, lesion and graft sizes, and suggest that PET can provide a useful tool for monitoring the viability of implanted striatal graft tissues in vivo.
Rats were trained on an operant task and then received striatal lesions and grafts. Grafts were d... more Rats were trained on an operant task and then received striatal lesions and grafts. Grafts were derived either from whole-ganglionic eminences or restricted to the lateral eminence. When retested 4 months later; graft-associated behavioural recovery was only apparent with extensive retesting. There was no difference in performance between rats that received whole-dissection or lateral-dissection grafts, and no correlation between performance and the amount of striatal-like (P-zone) tissue within the graft. It is suggested that P-zone reconstruction may be necessary, but not sufficient for behavioural recovery, which may additionally depend upon rehabilitative training.
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Papers by E. M. TORRES